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Estimation of conduction velocity of the spino-thalamic tract in man
Abstract
This is the first report of estimating conduction velocity (CV) of the slowly conducting somatosensory spinal tracts or the spino-thalamic tract (STT) in man. The CV of the STT was measured by recording somatosensory evoked potentials (SEPs) following CO2 laser stimulation of the hand and foot, which was previously shown to cause pain or heat sensation by activating cutaneous nociceptors and by its ascending signals through Aδ fibers and probably STT. When the CV of Aδ fibers was assumed to be 10–15 m/sec, the CV of STT was found to be approximately 8–10 m/sec in normal young subjects. It was slightly slower in subjects over 60 years of age. In contrast, the CV of the posterior column, which was calculated based on SEPs following electrical stimulation of the median and posterior tibial nerves, was approximately 50–60 m/sec.
... The brain responses evoked by a painful laser stimulus (late laser-evoked potentials, LEPs) are related to the activation of type II A␦ mechano-heat nociceptors (AMH II), small-myelinated primary neurons, and STT neurons. Late LEPs are widely used in physiological and clinical studies in patients with peripheral or central lesions (Bromm and Treede 1991; Iannetti et al. 2001a; Kakigi et al. 1991). ...
... We measured the conduction distance between the vertebral spinous processes and corrected it for the spine convexity (the real length of the spinal cord is on average 13% shorter than the length measured from the skin) (Desmedt and Cheron 1983; Kakigi and Shibasaki 1991). Spinal conduction time was taken from the latency of the main positive LEP component and the reaction times. ...
... Our estimated conduction velocity for spinal neurons that mediate the pinprick sensation (A␦ input) was relatively similar to velocities previously found with laser-stimulation methods measuring P latencies (about 10 m/s) (Kakigi and Shibasaki 1991; Rossi et al. 2000) or N latencies (about 20 m/s) (Cruccu et al. 2000) in humans and with direct recording of spinal and thalamic cells in primates (17–22 m/s) (Ferrington et al. 1987; Willis et al. 1974). The A␦-related volley ascends along the STT, the main pathway that conveys nociceptive information from the spinal cord to the forebrain (Craig and Dostrovsky 1999). ...
Nociception begins when Adelta- and C-nociceptors are activated. However, the processing of nociceptive input by the cortex is required before pain can be consciously experienced from nociception. To characterize the cortical activity related to the emergence of this experience, we recorded, in humans, laser-evoked potentials elicited by physically identical nociceptive stimuli that were either perceived or unperceived. Infrared laser pulses, which selectively activate skin nociceptors, were delivered to the hand dorsum either as a pair of rapidly succeeding and spatially displaced stimuli (two-thirds of trials) or as a single stimulus (one-third of trials). After each trial, subjects reported whether one or two distinct painful pinprick sensations, associated with Adelta-nociceptor activation, had been perceived. The psychophysical feedback after each pair of stimuli was used to adjust the interstimulus interval (ISI) of the subsequent pair: when a single percept was reported, ISI was increased by 40 ms; when two distinct percepts were reported, ISI was decreased by 40 ms. This adaptive algorithm ensured that the probability of perceiving the second stimulus of the pair tended toward 0.5. We found that the magnitude of the early-latency N1 wave was similar between perceived and unperceived stimuli, whereas the magnitudes of the later N2 and P2 waves were reduced when stimuli were unperceived. These findings suggest that the N1 wave represents an early stage of sensory processing related to the ascending nociceptive input, whereas the N2 and P2 waves represent a later stage of processing related, directly or indirectly, to the perceptual outcome of this nociceptive input.
... Previous studies-using heat and warm laser stimulation of the skin overlying the vertebral spinous processes-have investigated the spinothalamic tract in healthy humans and patients and provided information on nociceptive and warm spinal pathway conduction velocities (Cruccu et al., 2000;Iannetti et al., 2003;Kakigi & Shibasaki, 1991;Valeriani et al., 2011), related to Aδ-and C-fibres. Specifically, they found a nociceptive spinal pathway conduction velocity ranging from 9.9 to 21 m/s and warm spinal pathway conduction velocities ranging from 2.0 to 3.1 m/s. ...
... The two different methods used to calculate conduction velocities yielded similar results, showing velocities in the range of Aδ small myelinated fibres for cold and noxious heat stimulation and in the range of C unmyelinated fibres for warm stimulation. In our study, nociceptive and warm spinal pathway conduction velocities are consistent with previous observations in healthy humans that have found nociceptive spinal pathway conduction velocities ranging from 9.9 to 21 m/s and warm spinal pathway conduction velocities ranging from 2.0 to 3.1 m/s (Cruccu et al., 2000;Kakigi et al., 1991;Qiu, Inui, Wang, Tran, & Kakigi, 2001;Valeriani et al., 2011). Unexpectedly, we F I G U R E 4 Boxplots of the CVs computed with the two methods by type of stimulation (cold in blue, noxious in red and warm in purple). ...
Objectives
We aimed to investigate the conduction velocity of the cold spinal pathway in healthy humans.
Methods
Using a cold stimulator consisting of micro‐Peltier elements that was able to produce steep cooling ramps up to ‐300°C/s we recorded cold‐evoked potentials after stimulation of the dorsal midline at C5, T2, T6, and T10 vertebral levels and calculated the conduction velocity of the cold spinal pathway. In all participants, we used laser stimulation to deliver painful heat (Aδ‐fibres mediated) and warm (C‐fibres mediated) stimuli to the same sites in order to compare the conduction velocity of the cold spinal pathway with that of the nociceptive and warm spinal pathways.
Results
Cold stimulation evoked large‐amplitude vertex potentials from all stimulation sites. The mean conduction velocity of the cold spinal pathway was 12.0 m/s, which did not differ from that of the nociceptive spinal pathway (10.5 m/s). The mean conduction velocity of the warm spinal pathway was 2.0 m/s.
Discussion
This study provides previously unreported findings regarding cold spinal pathway conduction velocity in humans, that may be useful in the assessment of spinal cord lesions, as well as in intraoperative monitoring during spinal surgery.
... Additional differences in timing may arise from differences in receptor transduction times as well as the time required for that sensory input to reach the cortex. Considering nociception and vision, the slow conduction velocities of thinly-myelinated Aδ fibers (∼10 m/s [7]) and unmyelinated C fibers (∼1 m/s [8]) can be expected to introduce very large timing differences, especially when nociceptive stimuli are delivered to the distal end of a limb, i.e. when peripheral conduction distance is large. Visual information is transmitted to the cortex in less than 100 ms [9]. ...
... The current study explored, using the PSS of a TOJ task, the necessary asynchrony between the onset of a visual stimulus and the onset of a thermo-nociceptive stimulus activating Aδ-and/or C-fiber afferents for the two stimuli to be perceived at the same time by the participant. Indeed, sensory inputs transmitted to the cortex by the nociceptive system have far greater conduction times than sensory inputs transmitted by the visual system, especially for stimuli delivered to the distal end of a limb (i.e. when peripheral conduction distance is large), and for nociceptive inputs conveyed by unmyelinated C fibers (i.e. when peripheral conduction velocity is very slow) [7][8][9]. ...
Multisensory interactions between pain and vision allow us to adapt our behavior to optimize detection and reaction against bodily threats. Interactions between different sensory inputs are enhanced when they are perceived closely in space and time. However, thermo-nociceptive and visual stimuli are conveyed to the cortex through specific pathways with their own conduction velocity. The present experiment aims to measure the necessary asynchrony between a nociceptive stimulus and a visual stimulus for both to be perceived as occurring simultaneously. Healthy volunteers performed a temporal order judgment task during which they discriminated the temporal order between a laser-induced nociceptive stimulus applied on one hand dorsum and a visual stimulus presented next to the stimulated hand. Laser stimulus temperature selectively activated Aδ- and/or C- fiber afferents. In order to be perceived as occurring simultaneously with a visual stimulus, a thermo-nociceptive input selectively conveyed by C-fiber afferents must precede the visual stimulus by 577 ms on average, while the stimulus-evoked input conveyed by Aδ-fiber afferents must precede it by 76 ms on average. This experiment focuses on the necessary asynchrony between thermo-nociceptive and visual inputs for them to be perceived simultaneously, to optimize the conditions under which they interact closely. Since C-fibers are unmyelinated, the asynchrony between a C-fiber stimulus and a visual stimulus is much greater than the asynchrony between a nociceptive stimulus additionally activating Aδ-fibers and that same visual stimulus. It is crucial to consider these discrepancies in further studies interested in multisensory interactions.
... Since a wide range of laser stimulators have been developed so far (most common ones described above: 1.4 Laser stimulation as a method to activate heat-gated ion channels), the results obtained from them have shown different aspects of the nociceptive pathway. Studies using laser stimulation to investigate single neuron properties in primary afferents have been performed extensively during recent decades 10,50,56,94,95,113,114,118,[127][128][129][130] . Bromm and colleagues measured microneurographic recordings of primary afferents in the radial nerve in response to laser-heat stimulation on the receptive fields of identified units and observed that the largest receptor class which was activated by CO 2 laser stimuli were polymodal Cnociceptors 114 . ...
... Studies using laser-heat as a model to investigate the nociceptive system at the dorsal horn of the spinal cord [133][134][135] , and at the brain 91,99,110,114,115,127,[136][137][138][139][140][141][142][143] , used laser with beam diameters down to 1 mm. While Devor and coworkers observed mainly that dorsal horn neurons responding to laser-heat stimuli were located in superficial and deep zones from the dorsal horn, and were able to evoke potentials through signals mediated by C-polymodal nociceptors 133 ; Sikandar and collaborators extended those observations by recordings in dorsal horn neurons in the spinal segment L4-L5 in rodents and detected response latencies to different laser intensities mediated by both C-(in all power intensities) and Aδ-fiber afferents (only at higher power intensities) 134 . ...
Noxious heat is a natural stimulus that activates peripheral sensory neurons expressing heat-gated ion channels. Recently, the TRPM3 channel emerged as a noxious heat sensor independent of TRPV1, which is also sensitive to the neurosteroid Pregnenolone sulphate (PS). Recently, evidence of a direct mechanism that controls the agonist-induced TRPM3 channel activity by activation of the µ-opioid receptor (MOR) has been described, through direct binding of the G-beta-gamma subunit to TRPM3. The submitted thesis investigated mechanisms of heat-induced nociception using near-infrared laser stimulation as a rapid and accurate way to apply noxious heat. Responses to laser-heat were analyzed: in vitro by functional assays on heterologous expression systems and primary culture of sensory neurons, and in vivo by behavioral experiments and electrophysiological recordings at the dorsal horn of the spinal cord. Laser-heat activates TRPV1 and TRPM3 channels in heterologous expression systems with activation thresholds of about 574 µJ and 615 µJ. The response amplitudes of TRPM3 upon activation with PS exceeded those of maximum laser stimulation (1.5 ± 0.003 of the ratio 340/380 versus 0.66 ± 0.011). Chemical- and thermal- induced activity of the TRPM3 channel co-expressing the MOR was reduced with DAMGO by 63.4% and 44.5%. In DRGs, 15-25% of all neurons analyzed (n= 550) functionally co-expressed TRPV1 and TRPM3, 38% expressed TRPV1 independent of TRPM3, 7-8% expressed TRPM3 but not TRPV1. DRG neurons displayed a direct inhibition by 18 ± 4.1% and 23 ± 3% when co-applying the MOR agonist DAMGO with PS. In the dorsal horn of the spinal cord, the processing of peripheral laser stimulation was carried out by a subset of WDR and HTM neurons, which were found at all depths of the dorsal horn (range: 120-820 µm). Laser-heat stimuli induced pain-behavior in vivo. All neurons that responded to suprathreshold laser-heat were nociceptive, including one third of WDR neurons and half of HTM neurons investigated. No laser-heat responses of LTM neurons were found. The peripheral input of the laser sensitive neurons was composed of C- and A- fibers; however, responses to laser-heat were transmitted by C-fibers. The sizes of the heat receptive fields ranged 10% - 60% of the mechanical receptive field and they located always inside them. The number of AP following laser stimulation was higher in HTM neurons compared to WDR neurons (14 ± 0.7 vs 9 ± 4.3), however not significant, and the latencies after onset of the laser stimulation were 266 ± 16 ms and 308.3 ± 55. The estimated temperature threshold for laser sensitive WDR neurons and HTM neurons (40.1 °C and 43.3 °C) was comparable to the mean heat withdrawal threshold in awake rats (41 °C). Differences in the proportions of neurons expressing TRPM3 and/or TRPV1 could be responsible for those differences in receptive field sizes. Since the threshold for laser-heat activation of the TRPM3 channel was higher than the threshold for TRPV1, a greater proportion of peripheral neurons containing TRPM3 might converge in dorsal horn laser sensitive HTM neurons than for laser sensitive WDR neurons.
... For example, lamina I cold-sensitive neurons in the cat present a linear increase in their response to decreasing skin temperatures in the range of 34 • C to 15 • C, a fact which is well matched by human psychophysical results on thermosensory magnitude estimation (102). Also, conduction velocities of cat and monkey' spinothalamic cold-sensitive myelinated neurons (∼8 and ∼5.6 m/s, respectively) (67, 88) resemble estimated conduction velocities (∼10 m/s) of cold-sensitive myelinated fibers in the human spinothalamic tract (168,249). Finally, cat' spinothalamic warm-sensitive unmyelinated C-fibers (conduction velocities: 1.5-3 m/s) (5) resemble estimated conduction velocities of unmyelinated warm-sensitive C-fibers in the human spinothalamic tract (∼2.2 m/s) (159,168,249). Altogether, the primarily animal-based findings reviewed earlier provides evidence in support of the role and properties of the spinothalamic tract as both the main spinal pathway as well as the first level of central integration of thermoafferent information within the central nervous system of mammals amongst which humans. ...
... Also, conduction velocities of cat and monkey' spinothalamic cold-sensitive myelinated neurons (∼8 and ∼5.6 m/s, respectively) (67, 88) resemble estimated conduction velocities (∼10 m/s) of cold-sensitive myelinated fibers in the human spinothalamic tract (168,249). Finally, cat' spinothalamic warm-sensitive unmyelinated C-fibers (conduction velocities: 1.5-3 m/s) (5) resemble estimated conduction velocities of unmyelinated warm-sensitive C-fibers in the human spinothalamic tract (∼2.2 m/s) (159,168,249). Altogether, the primarily animal-based findings reviewed earlier provides evidence in support of the role and properties of the spinothalamic tract as both the main spinal pathway as well as the first level of central integration of thermoafferent information within the central nervous system of mammals amongst which humans. ...
Undoubtedly, adjusting our thermoregulatory behavior represents the most effective mechanism to maintain thermal homeostasis and ensure survival in the diverse thermal environments that we face on this planet. Remarkably, our thermal behavior is entirely dependent on the ability to detect variations in our internal (i.e., body) and external environment, via sensing changes in skin temperature and wetness. In the past 30 years, we have seen a significant expansion of our understanding of the molecular, neuroanatomical, and neurophysiological mechanisms that allow humans to sense temperature and humidity. The discovery of temperature-activated ion channels which gate the generation of action potentials in thermosensitive neurons, along with the characterization of the spino-thalamo-cortical thermosensory pathway, and the development of neural models for the perception of skin wetness, are only some of the recent advances which have provided incredible insights on how biophysical changes in skin temperature and wetness are transduced into those neural signals which constitute the physiological substrate of skin thermal and wetness sensations. Understanding how afferent thermal inputs are integrated and how these contribute to behavioral and autonomic thermoregulatory responses under normal brain function is critical to determine how these mechanisms are disrupted in those neurological conditions, which see the concurrent presence of afferent thermosensory abnormalities and efferent thermoregulatory dysfunctions. Furthermore, advancing the knowledge on skin thermal and wetness sensations is crucial to support the development of neuroprosthetics. In light of the aforementioned text, this review will focus on the peripheral and central neurophysiological mechanisms underpinning skin thermal and wetness sensations in humans. (C) 2016 American Physiological Society.
... The average distance between the forearm and the spinal cord (i.e., the C7 vertebra of the spine) was approximately 50 cm, and that between C7 and C1 was approximately 10 cm. Given that the CV of the Aδ fiber is 10-15 m/s (Kakigi and Shibasaki, 1991) and that of the Aβ fiber is 60 m/s (Inui et al., 2006), we estimated that it would take 42 ms more for the Aδ impulse to reach the spinal cord (we adopted the slowest CV of the Aδ fiber, i.e., 10 m/s for the calculation). Similarly, the CVs of the spinothalamic tract and the posterior column are 8-10 m/s and 50-60 m/s (Kakigi and Shibasaki, 1991), respectively. ...
... Given that the CV of the Aδ fiber is 10-15 m/s (Kakigi and Shibasaki, 1991) and that of the Aβ fiber is 60 m/s (Inui et al., 2006), we estimated that it would take 42 ms more for the Aδ impulse to reach the spinal cord (we adopted the slowest CV of the Aδ fiber, i.e., 10 m/s for the calculation). Similarly, the CVs of the spinothalamic tract and the posterior column are 8-10 m/s and 50-60 m/s (Kakigi and Shibasaki, 1991), respectively. Therefore, we estimated the difference in conduction time within the spinal cord to be 11 ms. ...
Recently, the cortical mechanisms of tactile-induced analgesia have been investigated; however, spatiotemporal characteristics have not been fully elucidated. The insular-opercular region integrates multiple sensory inputs, and nociceptive modulation by other sensory inputs occurs in this area. In this study, we focused on the insular-opercular region to characterize the spatiotemporal signature of tactile-induced analgesia using magnetoencephalography in 11 healthy subjects. Aδ (intra-epidermal electrical stimulation) inputs were modified by Aβ (mechanical tactile stimulation) selective stimulation, either independently or concurrently, to the right forearm. The optimal inter-stimulus interval (ISI) for cortical level modulation was determined after comparing the 40-, 60-, and 80-ms ISI conditions, and the calculated cortical arrival time difference between Aδ and Aβ inputs. Subsequently, we adopted a 60-ms ISI for cortical modulation and a 0-ms ISI for spinal level modulation. Source localization using minimum norm estimates demonstrated that pain-related activity was located in the posterior insula, whereas tactile-related activity was estimated in the parietal operculum. We also found significant inhibition of pain-related activity in the posterior insula due to cortical modulation. In contrast, spinal modulation was observed both in the posterior insula and parietal operculum. Subjective pain, as evaluated by the visual analog scale, also showed significant reduction in both conditions. Therefore, our results demonstrated that the multisensory integration within the posterior insula plays a key role in tactile-induced analgesia.
... Manfron et al. 2020a, b). The nociceptive system mainly consists of thinly myelinated Aδ fibers with a conduction velocity of ~ 10 m/s (Kakigi and Shibasaki 1991) and unmyelinated C fibers with a conduction velocity of ~ 1 m/s (Opsommer et al. 1999). When applying brief heat stimuli on the hand dorsum, the generated nociceptive inputs are expected to elicit their first cortical response at about 150 ms for inputs conveyed by Aδ fibers and at almost 1 s for inputs transmitted by C fibers (Plaghki and Mouraux 2005). ...
To protect our body against physical threats, it is important to integrate the somatic and extra-somatic inputs generated by these stimuli. Temporal synchrony is an important parameter determining multisensory interaction, and the time taken by a given sensory input to reach the brain depends on the length and conduction velocity of the specific pathways through which it is transmitted. Nociceptive inputs are transmitted through very slow conducting unmyelinated C and thinly myelinated Aδ nociceptive fibers. It was previously shown that to perceive a visual stimulus and a thermo-nociceptive stimulus applied on the hand as coinciding in time, the nociceptive stimulus must precede the visual one by 76 ms for nociceptive inputs conveyed by Aδ fibers and 577 ms for inputs conveyed by C fibers. Since spatial proximity is also hypothesized to contribute to multisensory interaction, the present study investigated the effect of spatial congruence between visual and nociceptive stimuli. Participants judged the temporal order of visual and nociceptive stimuli, with the visual stimuli flashed either next to the stimulated hand or next to the opposite unstimulated hand, and with nociceptive stimuli evoking responses mediated by either Aδ or C fibers. The amount of time by which the nociceptive stimulus had to precede the visual stimulus for them to be perceived as appearing concomitantly was smaller when the visual stimulus occurred near the hand receiving the nociceptive stimulus as compared to when it occurred near the contralateral hand. This illustrates the challenge for the brain to process the synchrony between nociceptive and non-nociceptive stimuli to enable their efficient interaction to optimize defensive reaction against physical dangers.
... The latency difference in early activations between pain and tactile stimulation (Fig. 3A) is considered to reflect the difference in conduction velocity between Ad and Ab fibers. 26,32,34 The absence of a significant difference in the late AI response (Fig. 3A) indicates that late activity is largely unaffected by nerve conduction velocities, suggesting that early and late activations have different origins. ...
Introduction:
Pain is a complex experience influenced by sensory and psychological factors. The insula is considered to be a core part of the pain network in the brain. Previous studies have suggested a relationship between the posterior insula (PI) and sensory processing, and between the anterior insula (AI) and cognitive-affective factors.
Objectives:
Our aim was to distinguish sensory and cognitive responses in pain-related insular activities.
Methods:
We recorded spatiotemporal insular activation patterns of healthy participants (n = 20) during pain or tactile processing with painful or nonpainful movie stimuli, using a magnetoencephalography. We compared the peak latency between PI and AI activities in each stimulus condition, and between pain and tactile processing in each response. The peak latency and amplitude between different movies were then examined to explore the effects of cognitive influence. A visual analogue scale was used to assess subjective perception.
Results:
The results revealed one clear PI activity and 2 AI activities (early and late) in insular responses induced by pain/tactile stimulation. The early response transmitted from the PI to AI was observed during sensory-associated brain activity, whereas the late AI response was observed during cognitive-associated activity. In addition, we found that painful movie stimuli had a significant influence on both late AI activity and subjective perception, caused by nonpainful actual stimulation.
Conclusions:
The current findings suggested that late AI activation reflects the processing of cognitive pain information, whereas the PI and early AI responses reflect sensory processing.
... Numerous studies have highlighted this relationship previously, generally confirming that nociceptive evoked potentials are smaller and longer with advanced age ( Creac'H et al., 2015 ;Di Stefano et al., 2017 ;Granovsky et al., 2016 ;Lagerburg et al., 2015 ;Rosner et al., 2018 ;Truini et al., 2005 ). This is thought to primarily reflect a progressive loss of nociceptors in the periphery ( Ceballos et al., 1999 ;Ochoa and Mair, 1969 ;O'Sullivan and Swallow, 1968 ;Yezierski, 2012 ) and a reduction in conduction velocity of the spinothalamic tract ( Kakigi and Shibasaki, 1991 ), which are both paralleled by changes observed for other measures of pain (e.g., thresholds) ( Chakour et al., 1996 ;Gagliese, 2009 ;Gibson and Farrell, 2004 ;Gibson and Helme, 2001 ). Across studies, however, the details of the relationship between age and Fig. 7. Simulation study findings: a small waveform and large waveform (40% larger amplitude, 20 ms earlier latency) were used to create 16 datasets. ...
Laser and contact heat evoked potentials (LEPs and CHEPs, respectively) provide an objective measure of pathways and processes involved in nociception. The majority of studies analyzing LEP or CHEP outcomes have done so based on conventional, across-trial averaging. With this approach, evoked potential components are potentially confounded by latency jitter and ignore relevant information contained within single trials. The current study addressed the advantage of analyzing nociceptive evoked potentials based on responses to noxious stimulations within each individual trial. Single-trial and conventional averaging were applied to data previously collected in 90 healthy subjects from 3 stimulation locations on the upper limb. The primary analysis focused on relationships between single and across-trial averaged CHEP outcomes (i.e., N2P2 amplitude and N2 and P2 latencies) and subject characteristics (i.e., age, sex, height, and rating of perceived intensity), which were examined by way of linear mixed model analysis. Single-trial averaging lead to larger N2P2 amplitudes and longer N2 and P2 latencies. Age and ratings of perceived intensity were the only subject level characteristics associated with CHEPs outcomes that significantly interacted with the method of analysis (conventional vs single-trial averaging). The strength of relationships for age and ratings of perceived intensity, measured by linear fit, were increased for single-trial compared to conventional across-trial averaged CHEP outcomes. By accounting for latency jitter, single-trial averaging improved the associations between CHEPs and physiological outcomes and should be incorporated as a standard analytical technique in future studies.
... 16 Similarly, the estimated conduction velocity of the spinothalamic tract is about 10-20 m/s. 17 However, the biggest disadvantage of laser stimulation is that it burns the superficial skin (erythema) with high intensity. In addition, both small-diameter myelinated Aδ fibers and unmyelinated C fibers are activated by a high-intensity CO 2 laser beam. ...
Pain is a conscious experience and a highly subjective sensation with a complex and often non‐linear relationship between nociceptive input and pain perception. Our understanding of the neural correlates of pain perception in humans has increased significantly since the advent of neuroimaging. Relating neural activity changes to the varied pain experiences has led to the concept that cognition, emotion, context, and injury can separately influence pain perception. In this mini review, the current concept of the central pain mechanism (CPM) is described. First, the concept of the “pain matrix” is stated: Nociceptive stimuli elicit responses in an extensive cortical network including somatosensory, insular, and cingulate areas, as well as frontal and parietal areas. Then, electrophysiological assessments of the CPM are reviewed based on the literature and our recent studies. In particular, supraspinal (cortical) mechanisms for pain perception and pain relief are outlined. The insular cortex has key roles in sensory‐associated as well as cognitive‐associated processing for pain perception.
... 11 Reduced synthesis and transport of neurotransmitters may delay transmission from peripheral structures to central nociceptive pathways 41 and has been proposed as an explanation for decreased conduction velocity in the spinothalamic tract in the elderly. 42 Because we observed that age-related increases of N2 and P2 latencies were only present on the distal areas (the feet) but not on the proximal areas (the thighs), we must admit that the effects of aging on LEPs depend, at least in part, on the length of the sensory fibers. Age-related desynchronization of nociceptive pathways may be more visible in the longest sensory fibers, leading to a lengthdependent increase in latency. ...
Introduction:
Aging has been reported to reduce the amplitude of laser evoked potentials. However, it is unknown whether this effect depends on the length of the sensory fibers. This is an important issue, because most painful neuropathies are length-dependent.
Methods:
We conducted a study of 40 healthy subjects, half of whom were older than age 50 years. Nociceptive stimuli were delivered to the feet and thighs using a CO2 laser stimulator.
Results:
Detection and pain perception thresholds did not correlate with age. Latencies of N1, N2, and P2 correlated positively with age on the feet but not on the thighs, whereas the amplitude of N2-P2 decreased with age for both areas.
Conclusions:
The effects of aging on latencies may reflect a distal loss of peripheral inputs and a length-dependent de-synchronization of the ascending nociceptive volley. Additional changes in peripheral and central processes may explain the diffuse decrease of N2-P2 amplitudes observed with aging.
... Future studies should examine whether comparison of the latencies of C-fibre LEPs elicited by stimulation of proximal vs distal segments of the same limb, by stimulation of the upper and lower limbs, or by stimulation of the dorsal skin innervated by different dermatomes could be used to obtain reliable Table 1 Latency and amplitude of C-fibre laser-evoked potentials after stimulation of the hand and foot dorsum. estimates of the conduction velocity of peripheral C-fibres and/or spinothalamic tracts [7,14,27,32,36]. Both when stimulating the hand and when stimulating the foot, the scalp topographies of the N2 and P2 peaks were maximal at the scalp vertex and were symmetrically distributed over both hemispheres. ...
C‐fibre laser‐evoked potentials can be obtained reliably at single‐subject level from the hand and foot using a temperature‐controlled CO2 laser combined with an adaptive algorithm based on reaction times. ABSTRACT: Brain responses to the activation of C‐fibres are obtained only if the co‐activation of Aδ‐fibres is avoided. Methods to activate C‐fibres selectively have been proposed, but are unreliable or difficult to implement. Here, we propose an approach combining a new laser stimulator to generate constant‐temperature heat pulses with an adaptive paradigm to maintain stimulus temperature above the threshold of C‐fibres but below that of Aδ‐fibres, and examine whether this approach can be used to record reliable C‐fibre laser‐evoked brain potentials. Brief CO2 laser stimuli were delivered to the hand and foot dorsum of 10 healthy subjects. The stimuli were generated using a closed‐loop control of laser power by an online monitoring of target skin temperature. The adaptive algorithm, using reaction times to distinguish between late detections indicating selective activation of unmyelinated C‐fibres and early detections indicating co‐activation of myelinated Aδ‐fibres, allowed increasing the likelihood of selectively activating C‐fibres. Reliable individual‐level electroencephalogram (EEG) responses were identified, both in the time domain (hand: N2: 704 ± 179 ms, P2: 984 ± 149 ms; foot: N2: 1314 ± 171 ms, P2: 1716 ± 171 ms) and the time‐frequency (TF) domain. Using a control dataset in which no stimuli were delivered, a Receiver Operating Characteristics analysis showed that the magnitude of the phase‐locked EEG response corresponding to the N2‐P2, objectively quantified in the TF domain, discriminated between absence vs presence of C‐fibre responses with a high sensitivity (hand: 85%, foot: 80%) and specificity (hand: 90%, foot: 75%). This approach could thus be particularly useful for the diagnostic workup of small‐fibre neuropathies and neuropathic pain.
... However, the participation of active thalamocortical processes cannot be ruled out; this is shown in Fig. 6, which depicts the discharge frequency of peripheral and central nociceptive neurons together with the COVAS ratings in our experiment. The neuronal discharge activity presented in Fig. 6 is derived from monkeys but the timing of the central neuronal events is not likely to be more than 2 s delayed in humans, given the similarity of the stimulation method and the estimated conduction velocities from the human STT to the cerebral cortex (average 2.9 m/s for C fiber stimulation; averages ranging from $10 to 21 m/s for Ad fiber stimulation [14,28,59,69]. ...
Noxious cutaneous contact heat stimuli (48 degrees C) are perceived as increasingly painful when the stimulus duration is extended from 5 to 10s, reflecting the temporal summation of central neuronal activity mediating heat pain. However, the sensation of increasing heat pain disappears, reaching a plateau as stimulus duration increases from 10 to 20s. We used functional magnetic resonance imaging (fMRI) in 10 healthy subjects to determine if active central mechanisms could contribute to this psychophysical plateau. During heat pain durations ranging from 5 to 20s, activation intensities in the bilateral orbitofrontal cortices and the activation volume in the left primary (S1) somatosensory cortex correlated only with perceived stimulus intensity and not with stimulus duration. Activation volumes increased with both stimulus duration and perceived intensity in the left lateral thalamus, posterior insula, inferior parietal cortex, and hippocampus. In contrast, during the psychophysical plateau, both the intensity and volume of thalamic and cortical activations in the right medial thalamus, right posterior insula, and left secondary (S2) somatosensory cortex continued to increase with stimulus duration but not with perceived stimulus intensity. Activation volumes in the left medial and right lateral thalamus, and the bilateral mid-anterior cingulate, left orbitofrontal, and right S2 cortices also increased only with stimulus duration. The increased activity of specific thalamic and cortical structures as stimulus duration, but not perceived intensity, increases is consistent with the recruitment of a thalamocortical mechanism that participates in the modulation of pain-related cortical responses and the temporal summation of heat pain.
Objective
Nociceptive stimuli have been studied either by dipolar modelling using electroencephalography (EEG) or magnetoencephalography (MEG), but rarely using both techniques simultaneously. This study aims to investigate the spatiotemporal representation of cortical activity in response to non-nociceptive (tactile) and nociceptive (laser) stimuli using parallel EEG-MEG recordings.
Methods
We performed simultaneous EEG and MEG recordings in 12 healthy subjects by applying pneumatic tactile and nociceptive laser stimuli on the right- and left-hand dorsum. We analyzed brain responses for both modalities and methods by means of global field power (GFP), and dipole source locations, strengths and orientations calculated in the depth to identify similarities and differences.
Results
Prominent GFP peaks were similar in EEG and MEG for tactile responses but different for nociceptive responses.
Conclusions
Methodically, MEG was superior to EEG in detecting the earliest nociceptive laser-evoked components with earlier latency in primary- and secondary somatosensory cortices, whereas EEG was superior to MEG in detecting late nociceptive components due to radially oriented deeper cortical activity.
Significance
EEG and MEG revealed in part differential nociceptive waveform patterns, peak latencies, and source orientations, making combined recordings favorable to examine pain-related activity as a whole in high temporal-spatial resolution.
Clinical neurophysiologic investigation of pain pathways in humans is based on specific techniques and approaches, since conventional methods of nerve conduction studies and somatosensory evoked potentials do not explore these pathways. The proposed techniques use various types of painful stimuli (thermal, laser, mechanical, or electrical) and various types of assessments (measurement of sensory thresholds, study of nerve fiber excitability, or recording of electromyographic reflexes or cortical potentials). The two main tests used in clinical practice are quantitative sensory testing and pain-related evoked potentials (PREPs). In particular, PREPs offer the possibility of an objective assessment of nociceptive pathways. Three types of PREPs can be distinguished depending on the type of stimulation used to evoke pain: laser-evoked potentials, contact heat evoked potentials, and intraepidermal electrical stimulation evoked potentials (IEEPs). These three techniques investigate both small-diameter peripheral nociceptive afferents (mainly Aδ nerve fibers) and spinothalamic tracts without theoretically being able to differentiate the level of lesion in the case of abnormal results. In routine clinical practice, PREP recording is a reliable method of investigation for objectifying the existence of a peripheral or central lesion or loss of function concerning the nociceptive pathways, but not the existence of pain. Other methods, such as nerve fiber excitability studies using microneurography, more directly reflect the activities of nociceptive axons in response to provoked pain, but without detecting or quantifying the presence of spontaneous pain. These methods are more often used in research or experimental study design. Thus, it should be kept in mind that most of the results of neurophysiologic investigation performed in clinical practice assess small fiber or spinothalamic tract lesions rather than the neuronal mechanisms directly at the origin of pain and they do not provide objective quantification of pain.
La douleur de la personne âgée est encore trop souvent sous-estimée car malévaluée et par conséquent insuffisamment soulagée. A travers une revue de la littérature, l'auteur tente de mettre en évidence la spécificitéà la fois clinique et thérapeutique de la prise en charge de la douleur de la personne âgée. Il présente une étude prospective portant sur cent-trente-huit personnes hospitalisées dans un service de long séjour. Les prescriptions d'analgiques ont été examinées durant cinq mois.l 'analyse des résultats montre que le paracétamol et les molécules appartenant au palier II occupent une large place dans l'arsenal thérapeutique et que la morphine et ses dérivés, jadis sous-employés, font partie aujourd' hui des traitements quotidiens. Les résultats ont été comparés à d'autres semblables retrouvés dans la littérature.Enfin, l'auteur fait part des nouvelles mesures et initiatives concernant ce sujetd 'avenir, ainsi que des avancées thérapeutiques de ces dernières années.
La douleur des sujets âgés est une situation fréquente est encore actuellement mal évaluée et insuffisamment prise en charge, particulièrement lorsqu'il existe des troubles de la communication verbale. La nature et la diversité des tableaux cliniques qu'elle revêt, les comportements des patients et des soignants à son égard, constituent autant d'obstacles à sa reconnaissance et à son traitement.Les urgences qui occupent une place prépondérante dans le système de soins en France, ne sont pas non plus étrangères à cette réalité. Une étude prospective, incluant 52 patients âgés de plus de 65 ans, a été menée à l'accueil des urgences du centre hospitalier de Lunéville (Meurthe et Moselle) de septembre à novembre 2006. Les résultats ont confirmé la tendance d'une sous-évaluation de la douleur et d'une oligo-analgésie. Plusieurs solutions peuvent être proposées concernant le recours à une infirmière d'accueil et d'orientation, la diffusion des outils d'hétéro-évaluation, l'utilisation du dossier médical et la mise en place d'un protocole de traitement.
A challenge to workers studying somatosensory evoked potentials (SEPs) is to record pain-related SEPs, that is, responses resulting from impulses ascending through small myelinated fibres1. A low power and long wavelength CO2 laser beam induces pain or heat sensation when applied to the skin, and several papers have reported SEPs induced by CO2 laser stimuli (pain SEPs). In this study, we attempted to analyse results of pain SEPs in normal subjects and in patients with myelopathies to establish the usefulness of pain SEPs for clinical application
Objective: To evoke cerebral potentials by stimulating nociceptive fibers with contact heat evoked potentials stimulator (CHEPS) and estimate the nerve conduction velocities of peripheral nerve fibers mediating these responses. Methods: Subjects were set in supine position. A heat-foil technology with a rapid rising speed at 70°C/s was used to elicit pain and contact heat evoked potentials (CHEP). Contact heat was delivered via one circular thermode (diameter 27 mm, area 573 mm). Thermal stimuli were sent at two intensity levels (49.5°C and 54.5°C) to three body sites; thenar eminence, the dorsum of hand and proximal volar forarm. Contact heat evoked potentials were recorded from Cz and Pz. A systemic effect between stimulus intensities and pain rating were observed, the main components of this evoked potential were observed. Nerve conduction velocity was calculated from latency difference of CHEP and center to center distance of distal and proximal stimulus arrays. Results: The pain intensity rating was 3.2 ± 0.3 and 4.4 ± 0.5 when thenar eminence was stimulated at the temperature of 49.5°C and 54.5°C respectively; the rating was 6.3 ± 0.8 and 7.2 ± 0.5 when the dorsum of hand and proximal volar forarm were stimulated at the temperature of 54.5°C. respectively. Three components, Cz/N550, Cz/P750 and Pz/P1000, were found in the evoked potentials. Nerve conduction velocities of the fibers were (12.9 ± 7.5) and (1.7 ± 0.4) m/s respectively, which were corresponding to those of A8 fiber and C fiber. Conclusions: CHEPs can be elicited reliably and stably. Velocities of peripheral nerve fibers demonstrate that A8 fiber and C fiber mediate the response.
Pain and itch are unpleasant somatic sensations, and, in particular, severe problems for patients with chronic pain and itch. It is important to understand how these sensations are perceived/modulated in the brain in order to develop treatments for chronic pain and itch. Magnetoencephalography (MEG) can be used to investigate pain- and itch-related cerebral processing with high temporal resolution (ms). Many pain researchers have investigated the temporal profiles of cortical activities evoked by noxious stimuli and discussed how neural signals associated with pain are processed in the brain. In addition, pain modulation by physical and physiological factors has also been of interest for pain researchers and has been investigated to understand the pain modulation system in the brain. Until recently, it was considered impossible to measure itch-related processing in the brain using MEG, because no itch stimulus was shown to be useful for MEG. However, a new stimulus to evoke the itch sensation by applying electrical stimuli to the skin was developed. This electrical method is reproducible and produces a steep rise in the itch sensation and, therefore, it is suitable for MEG recording. A MEG study using electrical itch stimuli demonstrated that the temporal profile of cortical activity evoked by itch stimuli was partly different from that evoked by pain. © 2014 Springer-Verlag Berlin Heidelberg. All rights are reserved.
Von der Kopfhaut des Menschen ableitbare somatosensible evozierte Potentiale (SSEP)1 wurden erstmals von Dawson (1947 a) beschrieben. Sie zeigten sich vorwiegend über der primären sensiblen Rinde kontralateral zur Seite der Stimulation lokalisiert (Abb. 2.1). Eine genauere Analyse dieser Reizantworten wurde erst nach Einführung elektronischer Mittelungsverfahren (Dawson 1954) möglich, bei denen die in fester zeitlicher Beziehung zum Reiz stehenden evozierten Potentiale aufsummiert, reizunabhängige Potentialschwankungen, wie das Grund-EEG oder Muskelartefakte, dagegen eliminiert werden. Auf diese Weise gelingt die Aufzeichnung und Messung niedrigster bioelektrischer Signale bis herab zu einer Größenordnung um 0,05 µV. Damit lassen sich die elektrischen Phänomene der Impulsgeneration und übermittlung in den somatosensiblen Anteilen des peripheren und zentralen Nervensystems von der Körperoberfläche aus abgreifen, was einen recht genauen Einblick in die Vorgänge der Impulsleitung und verarbeitung erlaubt.
Die evozierten Potentiale nach schmerzhaften Reizen sind eine Sonderform somatosensorisch evozierter Potentiale (SEP). Gegenüber den Standard-SEP zeichnen sie sich durch andere periphere und zentrale Leitungsbahnen aus (zur Übersicht s. Willis 1985): Schmerzhafte Reize aktivieren A3- und C-Fasern in peripheren Nerven. Diese primären Afferenzen werden bereits im Hinterhorn des Rückenmarks auf sekundäre Neurone umgeschaltet, deren Axone im kontralateralen Tractus spinothalamicus nach rostral projizieren. Diese Bahn verläuft weit lateral bis in den unteren Hirnstamm hinein und trifft erst kurz unterhalb des Thalamus auf den Lemniscus medialis. Deshalb können durch schmerzhafte Reize evozierte Potentiale in der neurologischen Topodiagnostik eine wichtige Ergänzung zu den SEP liefern.
Motor execution processing has been examined using an index of behavioral performance such as reaction times, kinetics, and kinematics. However, difficulties have been associated with the study of motor inhibitory processing because of the absence of actual behavioral performance. Therefore, non-invasive neurophysiological and neuroimaging methods including electroencephalography, magnetoencephalography, transcranial magnetic stimulation, and functional magnetic resonance imaging have been used to investigate neural processes in the central nervous system. We mainly reviewed research on somato-motor inhibitory processing based on data obtained by using these techniques, which can examine 'when', 'where, and 'how' motor inhibition occurs in the brain. Although to date a number of studies have used these techniques separately, few studies have utilized them in a comprehensive manner. In this review, we provide evidence that combining neurophysiological and neuroimaging methods should contribute to our understanding of how executive and inhibitory functions are implemented.
The non-phase locked EEG response to painful stimuli has usually been characterized as decreased oscillatory activity (event-related desynchronization, ERD) in the alpha band. Increased activity (event-related synchronization, ERS) in the gamma band has been reported more recently. We have now tested the hypothesis that the non-phase locked responses to non-painful electro-cutaneous stimuli are different from those to painful cutaneous laser stimuli when the baseline salience of the two stimuli is the same and the salience during the protocol is modulated by attention and distraction tasks. Both of these stimuli were presented in random order in a single train at intensities which produced the same baseline salience in the same somatic location. The response to the laser stimulus was characterized by five windows in the Time-frequency domain: early (200-400 ms) and late (600-1400 ms) delta/theta ERS, 500-900 ms alpha ERD, 1200-1600 ms beta ERS (rebound), and 800-1200 ms gamma ERS. Similar ERS/ERD windows of activity were found for the electric stimulus. Individual participants largely had activity in windows consistent with the overall analysis. Linear regression of ERS/ERD for parietal channels was most commonly found for sensory- (pain or unpleasantness) or attention- (salience) related measures. Overall, the main effect for modality was the result of activity in Windows I and V, and the modality with task interaction was found for all five windows. There was no significant interaction term which did not include modality. Therefore, the modality was the most common factor explaining of our results, which is consistent with our hypothesis.
The Focus article reported by Chen, Arendt Nielsen, and Plaghki clearly reviewed previous basic and clinical studies on laser-evoked poten tials (LEPs), mainly on LEPs following painful CO2 laser stimulation. They also proposed "standards for LEP measurements." This is an excellent review that will likely be very useful not only for researchers studying LEPs but also for general readers who are interested in the physiological pain studies in humans. We would like to provide some comments regarding this article and add some information that is not described in detail, although these may be reported in the second issue by the authors.
Pain-temperature sensation and other somatosensory sensations, such as touch or vibration, ascend through different peripheral and central pathways, so both pain SEP and pain SEF are useful for elucidating the pathophysiology of various types of sensory impairments. Somatosensory evoked potential (SEP) relating to pain (pain SEP) can be recorded by different types of lasers, including CO2 argon, Nd-YAG, and thulium laser. Differences among these types depend mainly on the wavelengths, as this parameter determines skin reflectance, absorbency, scattering, and transmittance (Chen et al. 1998a,b). Recently, CO2 laser stimulation (10.6 11m wavelength) has become popular. Other important factors causing a change of pain SEP waveforms are attention or distraction effects. The chapter describes these factors in brief and mentions several important findings. The amplitude of the P2 component is significantly reduced during sleep and during distraction (mental calculation or memorizing numbers). This change positively correlates with a decrease of visual analog scale (VAS). These results indicate that vigilance and attentiveness to the painful stimuli should be monitored during the acquisition of pain SEP.
This chapter discusses the central mechanisms underlying pain sensation and perception based on the physiological findings in normal subjects and patients with sensory disturbances. The conventional noxious stimuli, such as pinprick and touching the skin with a test tube filled with ice water activate not only the nociceptive receptors but also other kinds of somatosensory receptors, such as tactile and mechanical receptors. When electrical stimulation of the peripheral nerves is employed, the stimulus intensity must be extremely high to activate small nerve fibers, such as A-delta and C fibers, which mediate nociceptive input. Mechanisms of human nociception can be studied by the use of CO2 laser stimulation, which selectively activates nociceptive receptors, and by the use of various noninvasive techniques. Apart from the contralateral thalamus, at least several cortical areas, including the contralateral primary somatosensory cortex (SI), bilateral second somatosensory cortex (SII), anterior cingulated cortex, and insular cortices are involved in the pain sensation/perception.
Laser somatosensory evoked potentials (LSEP) evaluate the functional integrity of thermoalgic pathways by the specific stimulation of A delta and C nociceptive afferences. As compared to a CO2 laser, the thulium Yttrium Aluminium Garnet (YAG) laser may be conducted by an optic fiber, which allows easier access to the stimulated body sites. We present normative data on thulium YAG LSEPs recorded after stimulation of upper and lower limbs (N = 15). LSEPs were obtained with a stimulation intensity that was twice the nociceptive threshold at the upper limbs (UL) and one and a half at the lower limbs (LL). To ensure a stable attentional level, subjects were asked to estimate stimulus intensity after each stimulation. The nociceptive thresholds at upper and lower limbs were respectively 319 ± 65 mJ and 359 ± 95, and with the above methodology the LSEPs could be obtained in every subject. The latencies of N2 and P2 were respectively 199 ± 18 ms and 325 ± 37 ms at the UL, 239 ± 36 ms and 378 ± 38 ms at the LL. This method produced robust and reproducible results, and proved to be reliable for routine clinical use. To optimise response stability we propose that right/left stimulation be conducted following an ‘A-B-B-A’ procedure.
Conduction velocity of A delta fibers of the human peripheral nerves was measured by using pain-related somatosensory evoked potentials following CO2 laser stimulation. It was found to be approximately 9 m/s in the forearm as well as in the lower leg. Because conventional conduction study using electric stimulation reflects only functions of large myelinated fibers related to deep proprioceptive and tactile sensations, the present noninvasive and simple, novel method is the only laboratory examination currently available to investigate physiological functions of the small diameter fibers mediating pain-temperature sensations.
In Part I, this Focus article describes characteristics of laser-evoked brain potentials (LEPs) in human pain and examines some of the methodological inconsistencies. Evidence both cautioning and supporting the use of LEPs is contrasted. A host of neurological mechanisms clearly illustrates the relation of LEPs and pain processing: Lasers elicit selectively the cutaneous receptors of thin afferent fibers, the anterolateral spinal tract, and the lateral tracts of the brainstem. Implication for clinical use is briefly suggested. We raise three contending issues: (1) measurement standard, (2) association and dissociation of the LEP amplitude and pain, and (3) dynamic spatiotemporal specificity of LEPs. We conclude that LEPs may reflect nociceptive processing but may not be the entire pain experience. We emphasize the proper use of LEPs in understanding the mechanisms of nociceptive activation in pain experience. To achieve this, we address the technological advance required in studying the dynamic spatiotemporal specificity of LEPs and human pain.
Pain-related cortical potentials were evoked by skin stimulation of the face and the limbs with 5-ns–duration laser pulses delivered by a Q-switched Nd:YAG laser. Such laser pulses, in the nanosecond range, were able to induce pinprick pain sensations and to evoke reproducible laser evoked potentials (LEPs) without visible skin lesions for an energy density of less than 18 mJ/mm2. Low energy densities, around 10 mJ/mm2, were sufficient to reach the pain threshold and to induce LEP. The mean conduction velocity of the stimulated afferent fibers was close to 20 m/s, consistent with the stimulation of Aδ fibers. The amplitude of LEP correlated with pain perception rather than with energy density. The differences, such as wavelength and stimulus duration, between the Q-switched Nd:YAG laser we used and the lasers that are currently used in LEP studies (i.e., CO2, argon, or Tm:YAG lasers in the millisecond range) are discussed. Our study opens novel perspectives in the LEP field of research by using a new type of laser with a very short pulse duration. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24:496–501, 2001
The temporal and spatial processing of pain perception in human was traced by magnetoencephalography (MEG). We applied a painful CO2 laser beam to the forearm of 11 normal subjects, and estimated the activated areas using a single equivalent current dipole (ECD) at each time point, and a brain electric source analysis (BESA) as a spatio-temporal multiple source analysis method. The four-source model was found to be the most appropriate; sources 1 and 2 at the secondary sensory cortex (SII) contralateral and ipsilateral to the stimulation, and sources 3 and 4 at the anterior medial temporal area (probably the amygdalar nuclei or hippocampal formation) contralateral and ipsilateral to the stimulation, respectively. Activities in all 4 areas were temporally overlapped. Activity in the primary sensory cortex (SI) contralateral to the stimulated site was not identified. Activity in the cingulate cortex was also not clearly identified. These results are probably due to one or more of the following factors; (1) the cingulate cortex is too deep, (2) the ECDs generated in the cingulate cortex are mainly oriented radially, and (3) the ECDs generated in bilateral hemispheres interfere with each other. No significant or consistent magnetic fields were recorded after 500 msec following the stimulation, probably due to the complicated spatial and temporal overlapping of activities in multiple areas.
Cutaneous stimulation with CO2 laser pulses activates small diameter sensory afferents and evokes a pain-related potential best recorded from the vertex (Cz) of humans. We report here the first successful recording of pain-related laser evoked potentials (LEPs) from awake monkeys. Laser pulses with stimulus intensities adjusted to the lowest level giving reproducible cerebral responses were delivered to the shaved rail of three awake African green monkeys. The proximal and distal tail were stimulated to calculate the conduction velocity of the activated fibers. The effects of subcutaneous injections of morphine and cocaine on the LEPs were evaluated. The results indicate that reproducible LEPs, with a morphology similar to those obtained from humans, can be recorded from the awake monkey. The calculated conduction velocity of the activated fibers averaged 8.7 m/s, which is in the range of A delta fibers. Following subcutaneous morphine injections; the LEPs disappeared and were quickly restored to their
By means of somatosensory evoked brain potentials following painful CO2 laser stimulation (pain SEPs) and a pain visual analogue scale (VAS), we investigated changes in pain perception caused by noxious cooling of the skin in normal subjects. Pain SEPs were recorded from scalp electrodes following laser stimulation applied to the leg under various conditions as follows: (1) control (without any interference); (2) 46 °C foot (dipping the foot ipsilateral to the stimulated leg in hot water at 46 °C); (3) 0 °C foot (dipping the foot ipsilateral to the stimulated leg in ice water at 0 °C); and (4) 0 °C hand (dipping the hand contralateral to the stimulated leg in ice water at 0 °C). Marked decreases in amplitude of pain SEPs and VAS were observed under all conditions as compared with the control (P < 0.001); the degree of pain relief was significantly correlated with changes in pain SEPs. These changes were greatest in the ‘0 °C hand’ condition, followed in decreasing order by ‘0 °C foot’ and ‘46 °C foot’, and there was a significant difference between ‘0 °C hand’ and the ‘46 °C foot’ condition. We considered that the decrease in pain is due to the diffuse noxious inhibitory control (DNIC). The reason why the degree of pain relief in ‘0 °C foot’ condition was less than that in ‘0 °C hand’ condition is unclear, but some particular spatial summation of two kinds of nociceptive impulses mediated by the same pathway might take place.
After a painful CO2 laser stimulation to the skin, the magnetoencephalography (MEG) response (164 ms in average peak latency) was not affected by distraction, but the sequential electroencephalography (EEG) responses (240–340 ms), probably generated by a summation of activities in multiple areas, were markedly affected. We suspect that the MEG response, whose dipole is estimated in the bilateral second somatosensory cortex (SII) and insula, reflects the primary activities of pain in humans.
The initial somatosensory evoked magnetic fields following painful heat stimulation by CO2 laser beam applied to the upper and lower limb were investigated in normal subjects. The main deflections, ‘Pain MA’ and ‘Pain ML’ following the arm and leg stimulation, respectively, were identified in the bilateral second sensory cortices (SII). The onset latencies of Pain MA and Pain ML were approximately 150 and 200 ms, respectively. No consistent equivalent current dipole was found in other areas including the primary sensory cortex in each hemisphere. Therefore, we consider that neurons in the bilateral SII are initially activated following painful heat stimulation.
The choice of a system specific stimulus is difficult when investigating the human nociceptive system, in contrast with the tactile, auditory and visual systems, because it should be noxious but not actually damage the tissue. The discomfort accompanying system specific stimulation must be kept to a minimum for ethical reasons. In this review, recent progress made in the study of human pain perception using intraepidermal electrical stimulation (IES) is described. Also, whether IES is a viable alternative to laser stimulation is discussed. IES selectively activates Aδ nociceptors, elicits a sharp pricking sensation with minimal discomfort and evokes cortical responses almost identical to those produced by laser stimulation. As IES does not require expensive equipment, and is easy to control, it would seem useful for pain research as well as clinical tests.
Lasers can selectively activate the nociceptors of A-delta fibers. Since nociceptors in the skin are activated via temperature conduction by the laser beam, a latency jittering of cortical responses among trials would affect results obtained with a conventional averaging (C-AVE) technique. We therefore used a new method, latency-adjusted averaging (L-AVE), to investigate cortical responses to noxious laser stimulation in normal subjects. L-AVE was done by averaging trials after adjusting the latency so that the peak latency of an activity in the temporal region of all trials matched on the time axis. Both in C-AVE and in L-AVE, clear activations were found in the contralateral primary somatosensory cortex (SI) and bilateral parasylvian regions, whose activities peaked 163-181 ms after the stimulation. In addition to these three main activities, weak activities peaking at around 109-119 ms could be identified in only L-AVE in similar cortical regions. Since the direction of the source differed between early and main activities, we considered that the early weak activities were cancelled out by the later main activities with an opposite orientation. The results suggested that early cortical processing of noxious information occurs earlier than previous neurophysiological studies have estimated and that the temporal sequence of activations should be reconsidered.
The diffuse noxious inhibitory control (DNIC) effect is the neurophysiological basis for the phenomenon that heterotopic "pain inhibits pain" in remote areas of the body. The effect of DNIC is mediated by spino-bulbo-spinal loops and a final postsynaptic inhibitory mechanism. The DNIC effect depends on intensity, duration, quality, and application site of conditioning stimulation and stimulated nerve fiber-type. DNIC induced by CO(2) laser conditioning stimulation has, however, not yet been investigated, and the present study was designed to examine this.
As the indicator of test stimulation, the late component of somatosensory evoked potentials (SEPs) induced by electrical tooth stimulation and pain intensity were examined under CO(2) laser conditioning stimulation. As the conditioning stimuli, CO(2) laser energy (lambda = 10.6 microm, spot size Ø = 2 mm) was applied to the dorsum of the left hand.
The maximum reductions in SEP amplitude and pain intensity evaluated using a visual analog scale were 34.7% and 28.7%, respectively during CO(2) laser conditioning stimulation. No aftereffect was observed.
The present study revealed that CO(2) laser radiation attenuated the late component of SEPs induced by electrical tooth stimulation, triggering the DNIC effect but with no aftereffect.
The objective of this study was to investigate whether no-go potentials during go/no-go tasks were observed after painful stimulation using intraepidermal electrical stimulation. Event-related potentials were recorded by stimulating the medial or lateral side of the left-hand dorsum. Peak amplitudes of N2 and P3 were significantly larger in no-go trials than in go trials at frontocentral electrodes during go/no-go task, but the differences were not found during rest control and choice reaction time tasks. These characteristics of no-go-related potentials were very similar to event-related potential waveforms during visual, auditory, and somatosensory go/no-go tasks. We suggest that cortical activities relating to response inhibitory processing are not dependent on the sensory modality used.
The use of diffusion tensor imaging with three-dimensional fibre tracking (DTI-FT) was tested for the assessment of spinal sensory tract lesions. The relationships between tract lesions quantified with DTI-FT were systematically examined, and somatosensory dysfunction was assessed with quantitative sensory testing (QST) and laser-evoked potentials (LEP), in patients with syringomyelia.
28 patients with cervical syringomyelia and thermosensory impairment of the hands, and 19 healthy volunteers, were studied. A DTI-FT of the spinal cord was performed, focusing on the upper segment (C3-C4) of the syrinx. Three-dimensional DTI-FT parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) of the full, anterior and posterior spinal cord were individually compared with QST (thermal detection thresholds) and LEP (amplitude, latency and spinothalamic tract (STT) conduction time) of the hands.
Patients had a significantly lower FA, but not ADC, than healthy subjects. The mean FA of the full section of the spinal cord was correlated both to sensory deficits (ie, increase in warm (rho = -0.63, p<0.010) and cold thresholds (rho = -0.72; p<0.001 of the hands)) and to changes in LEP parameters, in particular STT conduction time (rho = -0.75; p<0.010). Correlations between FA and the clinical and electrophysiological measures were higher in the anterior area (where the spinothalamic tracts are located) than in the posterior area of the spinal cord.
The data indicate that diffusion tensor imaging with 3D-fibre tracking is a new imaging method suitable for the objective and quantitative anatomical assessment of spinal somatosensory system dysfunction.
Pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation were examined in 30 patients with peripheral neuropathies, and the results were compared with clinical sensory findings. Pain SEP findings showed a significant correlation with the clinical impairment of pain sensation, but not with the impairment of deep sensations. In contrast, conventional electrically-stimulated SEPs (electric SEPs) showed a significant correlation with deep sensations, but not with the impairment of pain sensation. Examinations of both pain SEPs and electric SEPs, therefore, are considered to be very useful to evaluate physiological functions of sensory nerves in patients with peripheral neuropathies.
Physiological functions of the spinothalamic tract (STT) and the posterior column (PC) were studied in 19 Japanese patients with HTLV-I-associated myelopathy (HAM). The former was evaluated by pain-related somatosensory evoked potentials (SEPs) following CO2 laser stimulation, and the latter by conventional SEPs following electrical stimulation. Conduction velocity of STT and PC was significantly decreased in 9 and 14 patients, respectively, and more than half of them showed no clinical impairment of sensations (subclinical abnormality).
This is the first paper to study the physiological function of the spinothalamic tract in multiple sclerosis (MS) using pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation. Among 12 patients with MS, hand- and foot-stimulated pain SEPs were significantly delayed or absent in 3 and 7, respectively. These results were totally consistent with clinical impairment of pain-temperature sensation. In contrast, the results of conventional electrically-stimulated SEPs were compatible with impairment of vibration sensation. Therefore, the examination of both pain and electric SEPs is very useful to evaluate the physiological function of the ascending spinal tract in patients with MS.
Mechanisms of pain relief induced by vibration and movement were investigated. A CO2 laser beam, which is useful for pure nociceptive stimulation, was used for recording pain-related somatosensory evoked potentials (pain SEPs) and for measuring pain threshold and reaction time (RT). Concurrently applied vibratory stimuli to and active movements of the fingers significantly reduced and prolonged pain SEPs, increased pain threshold, and prolonged RT, indicating that an increase in the inhibitory mechanisms of painful feeling was induced by the concurrently adopted sensory inputs mediated by large myelinated fibres. In contrast, continuous cooling enhanced pain SEPs and decreased pain threshold, probably due to the spatial summation of two kinds of nociceptive impulses mediated by the same pathways. The results of this investigation throw light on the mechanisms of the alleviation of pain by vibration and movement.
Pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation as well as conventional electrically stimulated SEPs (electric SEPs) were examined in 10 patients with peripheral neuropathies in whom the histopathological examination of the sural nerve was done. Results of pain SEPs showed a positive relationship with clinical impairment of pain sensation and densities of small myelinated fibers of the sural nerve. In contrast, results of electric SEPs showed a positive relationship with clinical impairment of deep and tactile sensations and with densities of large myelinated fibers of the sural nerve. Therefore, pain SEPs are considered to be generated by ascending signals mediated through nociceptive receptors and A delta fibers. The pain SEP is only one noninvasive and objective method currently available to investigate a physiological condition of the sensory pathway responsible for pain sense, and is especially useful when combined with the conventional electric SEPs.
Compared volleys induced by artifical stimuli can be recorded from peripheral nerves of human subjects with extraneural electrodes. In contrast, the study of the normal traffic of impulses requires other methods. A powerful technique for recording this type of activity with percutaneously inserted intraneural electrodes was introduced in 1966. The development of the technique was promoted by interest in studying somatosensory and proprioceptive mechanisms in organisms with an intact sensorium and intact volition, particularly human subjects. This method opened up the possibility of investigating a number of neural mechanisms and is has been used mainly for studies of proprioceptive mechanism, tactile and nociceptive cutaneous activity, and efferent sympathetic discharges. In addition, cutaneous thermosensitive activity and oral mechanosensitive activity have been analyzed. Single-unit activity has been recorded from large myelinated nerve fibers and from unmyelinated nerve fibers, whereas rather few recordings from small myelinate fibers have been reported. In addition, multiunit activity from myelinated and unmyelinated fibers has been studied. Pathological mechanisms as well as normal conditions have been analyzed. Our aim here is to review findings extracted by recording impulses in human nerves with emphasis on the implications these findings may have on current theories within a number of fields. As far as it is feasible, the findings from human subjects are related to knowledge based on studies in other species. This review is based on reports published or known to be in the process of publication when the article was being written.
To elucidate the sensitivity to pain stimuli in patients with cortical reflex myoclonus, pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation and conventional electrically-stimulated SEPs (electric SEPs) were compared in four patients with cortical reflex myoclonus. The P25 peak of electric SEPs was considerably enhanced but the P320 potential of pain SEPs was of normal amplitude in all patients. After medication, myoclonus was reduced and the amplitude of P25 was decreased, but P320 showed no change. In our previous study of the scalp distribution in normal subjects, a subcortical site, probably the thalamus, was considered to be the generator source of P320. Because most pain stimuli do not reach the cortex, patients with cortical reflex myoclonus are not sensitive to pain stimuli and P320 in pain SEPs is not enhanced.
Conduction velocity of A delta fibers of the human peripheral nerves was measured by using pain-related somatosensory evoked potentials following CO2 laser stimulation. It was found to be approximately 9 m/s in the forearm as well as in the lower leg. Because conventional conduction study using electric stimulation reflects only functions of large myelinated fibers related to deep proprioceptive and tactile sensations, the present noninvasive and simple, novel method is the only laboratory examination currently available to investigate physiological functions of the small diameter fibers mediating pain-temperature sensations.
Scalp topography of somatosensory evoked potentials following mechanical (SEPs(M)) and electrical (SEPs(E)) stimulation of the left middle finger was investigated with linked ear reference in 21 normal young adults. A small plastic ball (touch) or needle (pain) was used for the mechanical stimulation. With mechanical stimulation, at least 3 positive and 3 negative potentials (P19(M), N24(M), P29(M), N36(M), P49(M) and N61(M)) were found in the post-rolandic area contralateral to the stimulation. The wave form in SEPs(M) was similar to those in SEPs(E), but the peak latency of each component in SEPs(M) was 1–4 msec longer than that in SEPs(E). Earlier components such as P19(M), N24(M) and P29(M) were not as clearly recognized as corresponding components in SEPs(E). However, the wave form recorded on the hemisphere ipsilateral to the stimulation or in the frontal area contralateral to the stimulation showed a greater difference from subject to subject. P19(M), N24(M) and P29(M) correlated positively both with arm length and height of the subject. There was no significant difference of the wave form between the linked ear reference and the bipolar (C4-Fz) derivation. Wave form of SEPs(M) by needle stimulation did not significantly differ from that by plastic ball stimulation.
Short latency somatosensory evoked potentials (SEPs) following posterior tibial nerve stimulation at the ankle were studied by using surface electrodes placed on the spine and scalp with a non-cephalic reference (unipolar recording) in normal young adults. In order to improve recording technique, ECG was used to trigger the stimulator, and bilateral simultaneous stimulation was employed. A triphasic (positive-negative-positive) or biphasic (negative-positive) potential was recorded at each spinal electrode. Latency of this potential was longer in the more rostral channels. Conduction velocity of the spinal cord from the 12th thoracic to the 2nd cervical spine was 73.4 ± 7.53 m/sec. At scalp electrodes, 4 components (P25, N27, P28 and N31) were identified preceding the major positive peak (P36). These 4 components showed similar latency and amplitude at all 4 electrodes investigated (Fs, Fz, C3 and C4) and are considered to be generated in the deep structure. Especially, P25 is estimated to be generated in the ascending sensory pathway of the upper cervical cord, but generator sources of other components remain to be determined, P36 appears to be generated in the somatosensory foot area.
Frontal and parietal SEPs to electrical stimulation of fingers were studied in conjunction with the spinal SEP and sensory nerve action potentials in 25 young adults and 19 healthy octogenarians. Limb temperatures were 36–37°C. Intersubject variations of SEP wave forms and detailed scalp topography helped delineate several genuine SEP components, namely the P25, N32 and N40, at precentral scalp sites. The parietal ‘W’ pattern (P30-N35-P45) was recorded in only 48% of the young, but 90% of the old subjects. All parietal components were significantly increased in size in the old, which contrasts with the reduced spinal SEP and sensory nerve potentials (Table II). The precentral SEP components were either maintained (P25) or reduced (N32). The primary afferent neurones appeared to age at a faster rate (CV reduced about 0.16 m/sec/year) than the second or third afferent neurones (no significant change in transit time from spinal entry to postcentral cortex or in mean central CV) (Table I).
A non-invasive, indirect method for measuring spinal cord mixed afferent-efferent conduction is described. The method is based upon eliciting late reflex responses labelled R1 and R2 from voluntarily contracting thenar and tibialis anterior muscles by preferentially stimulating median and common peroneal sensory nerve fibers. The mean onset latencies of R1 measured 27.5 msec and 30.6 msec recorded from hand and leg muscles respectively. R2 mean onset latencies measured 46.0 msec and 65.1 msec respectively. R1 has characteristics similar to an H-reflex. R2 is a long-loop reflex of unknown pathway assumed to involve similar circuits and rostral turn around points when elicited by both arm and leg stimulation. Mean spinal cord conduction time between the seventh cervical and fifth lumbar spinous processes, is given by (R2 leg - R1 leg) 2 - (R2 arm - R1 arm) 2 It measured 7.95 msec and the calculated mean conduction velocity was 57.9 ± 5.7 m/sec.
Somatosensory evoked potentials (SEPs) were elicited by stimulation of the right posterior tibial nerve at the ankle in 20 experiments on 18 normal adults. A non-cephalic reference on the left knee was used throughout (with triggering of averaging cycles from the ECG), except for recording the peripheral nerve potentials. The responses were recorded along the spine, from oesophageal probes and from the scalp. The peripheral nerve volley propagated at a mean maximum conduction velocity (CV) of 59.2 m/sec served to identify the spinal entry time (mean 19.7 msec) at spinal segments S1–S3, under the D12 spine. This entry time coincided with the onset of the N21 component which was interpreted as the dorsal column volley and considered equivalent to the neck N11 of the median nerve SEP. The large voltage of the spinal response at the D12 spine probably results from summation of N21 with a fixed latency N24 potential that phase reverses at oesophageal recording sites into a P24. The N24-P24 reflects a horizontal dipole in the dorsal horn and is equivalent to the N13-P13 of the neck SEP to median nerve stimulation. Spinal conduction between D12-C7 spines was spuriously overestimated because the true length of the dorsal spinal cord is shorter by about 13% than the distance measured on the skin over the dorsal convexity. This correction should be applied routinely and it leads to a mean maximum spinal CV of 57 m/sec. Several positive far fields with widespread scalp distribution and stationary latencies have been identified. The P17 (over spine and head) reflects the peripheral nerve volley at the upper buttock. The P21 is synchronous with the N21 at the D12 spine and reflects the initial volley in the dorsal column. No far-field equivalent has been found for the N24-P24, due to the horizontal axis of the corresponding dipole. The P26 far field reflects the ascending volley at spinal levels D10-D4. The P31 reflects the initial volley in the medial lemniscus. The P40 at Cz represents the cortical response of the foot projection. Average central CVs were calculated and discussed.RésuméDes potentiels évoqués somesthésiques (PES) ont été évoqués par stimulation du nerf tibial postérieur droit au niveau de la cheville dans 20 expériences sur 18 sujets adultes normaux. Une référence non-céphalique sur le genou gauche a été utilisée pour toutes les dérivations (avec déclenchement des époques par l'ECG), sauf celles des potentiels de nerf périphérique. Les PES ont été dérivés le long de la colonne vertébrale et au niveau du cuir chevelu ainsi que par des électrodes oesophagiennes. La vitesse de conduction maximale (VC) de la volée nerveuse périphérique (59,2 m/sec) a servi à identifier le moment d'entrée de la volée dans la moelle aux niveaux S1–S3, sous l'épine de la vertèbre D12. Ce moment d'entrée correspond au début de la composante N21 qui représente la volée dans le cordon postérieur et est équivalente au N11 dérivé à la nuque pour le PES du nerf médian. Le grand voltage de la réponse en D12 résulte de la sommation du N21 avec un potentiel N24 de latence fixe qui présente une inversion de polarité (en P24) aux électrodes oesophagiennes. Le N24-P24 reflète un dipôle d'axe horizontal dans la corne postérieure, et est l'équivalent du N13-P13 du PES nucal du nerf médian. La conduction spinale de D12 à C7 était surestimée de façon incorrecte parce que la longueur réelle de la moelle dorsale est inférieure d'environ 13% à la distance mesurée sur la peau de la convexité du dos. Cette correction devrait être appliquée en routine, et elle conduit à une VC spinale de 57 m/sec jusqu'en C7. Plusieurs potentiels de champ lointain positifs ont été identifiés. Le P17 (sur la colonne et la tête) reflète la volée du nerf périphérique au niveau du tiers supérieur de la fesse. Le P21 est synchrone au N21 dérivé sur D12 et reflète la volée débutante dans le cordon postérieur. Il n'y a pas de potentiel de champ lointain qui corresponde au N24-P24 dont le dipôle a un axe horizontal. Le potentiel de champ lointain P26 reflète la volée ascendante aux niveaux spinaux D10 à D4. Le potentiel de champ lointain P31 reflète la volée débutante dans le ruban de Reil médian. Le P40 au vertex représente la réponse corticale de la projection du pied. Les vitesses de conduction moyennes centrales ont été calculées et discutées.
A method is described for deriving an indirect estimate of the velocity of impulse propagation in the spinal cord of intact man. The estimate is computed from measurements of motor and sensory nerve conduction velocity in the limbs, F-wave latencies, and the latencies of somatosensory evoked potentials. The mean estimated spinal cord conduction velocicy in normal subjects was found to be 55.1 m/sec, with a standard deviation of 9.9. This method appears to have potential application in the electrophysiological evaluation of patients with myelopathic disorders.
Short latency evoked potentials were recorded from sites overlying the cervical and thoracic vertebrae, the clavicles, mastoid processes and cerebral cortex, following percutaneous stimulation of median nerve fibres at the elbow, wrist and fingers in 23 normal subjects. At least four major early components each with simultaneous positive and negative constituents, plus the first component (N20) of the cortical response, were all found to be mediated by sensory afferent fibres with conduction velocity 65--75 m/sec in the forearm of one subject. Study of the distribution of these potentials, using reference electrodes located at Fz or over the lower part of the spine, has led to the proposal of generator sites in the brachial plexus (N9), spinal roots or dorsal columns (N11), spinal grey matter or brain stem (N13), and brain stem or thalamus (N14). Comparison with intrathecal recordings in man lends support to the view that N11 and N13 are generated in or adjacent to the spinal cord. It is hoped the findings may extend the clinical applications of a non-invasive technique for investigating the afferent sensory pathways in man.
Percutaneous stimulation of the posterior tibial nerve at the ankle (2 per sec and 2–3 times sensory threshold voltage) was found to evoke consistent potentials over the spine in 10 out of 12 normal subjects. Using a midfrontal reference the most prominent features were a localised negative potential maximally recorded over L1 (mean peak latency 22.6 msec) and a more widespread negativity maximal in the cervical region (30.7 msec). A further negative component of intermediate latency was recorded from the mid-thoracic region to C2.
Somatosensory evoked potential (SEP) latencies, motor and sensory nerve conduction velocities (CVs), and F-wave latenies were measured in 15 elderly normal subjects (mean age 74.1 years), and the results were used to derive indirect estimates of spinal cord CVs. These measurements were compared to those from 15 younger normal adults (mean age 31.6 years), and the nerve conduction characteristics of all 30 subjects were analyzed with respect to age. Peripheral motor and sensory CVs slowed progressively, and the onset latencies of F-waves and SEPs increased gradually with advancing age. Spinal cord CVs showed little change until approximately age 60, and declined sharply thereafter. In addition, the latencies of F-waves and SEPs were positively associated with height. Human clinical and experimental studies utilizing SEP and F-wave measurements must allow for morphologic differences between individuals, and for the systematic changes which accompany normal aging.
t The myelinated primary afferent fibers arising from cells of the spinal dorsal root ganglia (DRG) have been thought to have generally constant fiber diameter and, hence, constant conduction velocity over their entire course6 except for branching terminally within the spinal cord17 and peripherally near the receptors. A similar assessment for motor neuron axons has recently been challenged by physiologic data showing a 25 % decrease in conduction velocity for the segment between brachial plexus and spinal cord in the baboon1. The same authors further claimed to have evidence for similar proximal slowing in myelinated afferents from evoked potential recordings in dorsal roots, although they presented no data on the subject. In this study, conduction velocities were measured in the distal and proximal processes of individual DRG cells. Eleven adult male and female cats were surgically prepared by L4-S1 laminectomy under deep pentobarbital anesthesia while position- ed in a stereotaxic frame. During the experiment, the animal was paralyzed with Flaxedil and artificially ventilated; the temperature of the body and the mineral oil- filled spinal pool were maintained automatically at 36-38 "C. Bipolar stimulating electrodes (pairs of platinum hooks) were placed on the distal stump of the cut right L7 dorsal root and on the sciatic nerve which was dissected free but left intact in the posterior groove between the hamstrings. Monophasic electrical pulses (0.1 or 0.3 msec duration) from isolated bipolar constant current stimulators were always deliver- ed using the hoolc closest to the ganglion as cathode. Conduction distances were I measured in situ at the end of each experiment by laying a piece of string from the cathode to the center of the ganglion. Dorsal root distances varied from 15 to 22 mm and sciatic nerve varied from 91 to 133 mm. The methods are described in greater I detail elsewherel3. Extracellular single unit records were obtained with glass insulated platinum- iridiumz1 or Parylene insulated tungsten14 microelectrodes which were inserted in pairs into the intact L7 DRG. Filtering and differential recording were used to cancel the mass potential evoked by synchronous electrical activation of the DRG cells, and single ganglion cell soma potentials were clearly discernible at threshold as all-or-
Brief pulses of Laser emitted radiant heat were used to induce cutaneous painful sensations in human volunteers. Accurate timing of the stimuli permitted recording of scalp averaged evoked potentials. A late negative-positive component of the EP which correlated in amplitude with the subjective sensation was observed in four subjects. The latency of this component (130-160 msec) correlated with stimulus intensity.
Pain-related somatosensory evoked potentials (pain SEPs) following CO2 laser stimulation as well as conventional electrically stimulated SEPs (electric SEPs) were examined in 10 patients with peripheral neuropathies in whom the histopathological examination of the sural nerve was done. Results of pain SEPs showed a positive relationship with clinical impairment of pain sensation and densities of small myelinated fibers of the sural nerve. In contrast, results of electric SEPs showed a positive relationship with clinical impairment of deep and tactile sensations and with densities of large myelinated fibers of the sural nerve. Therefore, pain SEPs are considered to be generated by ascending signals mediated through nociceptive receptors and A delta fibers. The pain SEP is only one noninvasive and objective method currently available to investigate a physiological condition of the sensory pathway responsible for pain sense, and is especially useful when combined with the conventional electric SEPs.
Spinal- and scalp-recorded somatosensory evoked potentials following stimulation of the posterior tibial nerve were obtained in 20 normal young subjects, and 45 aged subjects who were classified into group A (61-74 years) and group B (75-88 years). The results may be summarized as follows: (1) Spinal potentials, N19 at the twelfth thoracic vertebra and N28 at the second cervical vertebra, were significantly prolonged in latency in aged subjects. The interpeak latency, N19-N28, which represents the conduction time through the spinal cord, was also prolonged in aged subjects. (2) The interpeak latencies, P28-N31 and P28-P35, which represent the conduction time from the medial lemniscus to the thalamus and to the sensory cortex, respectively, were prolonged in aged subjects, particularly in group B. (3) The interpeak latencies of cortical potentials following P35, which represent the intracortical transit times, did not show any significant difference between young and aged subjects. (4) Amplitudes of the spinal, and short- and middle-latency cortical potentials were smaller in the aged subjects than those of young subjects, particularly the far-field N31 potential at Cz' electrode. In contrast, the long-latency cortical potentials were larger in aged subjects, although not significantly so.
Late components of cerebral potentials evoked by brief heat pulses applied to various skin sites were used to monitor the afferent pathways of pain and temperature sensitivity. Radiation at 10.6 micron wave length generated by a CO2 laser stimulator predominantly activates superficial cutaneous A delta and C nociceptors and elicits late and ultralate cerebral potentials. This paper deals with the investigation of the component structure and topography of the A delta fibre mediated late potentials, which were compared with the corresponding late potentials in response to standard electrical nerve stimuli. In the upper limb both stimulus types evoked a large positive potential (nerve: 260 msec, skin: 390 msec latency), preceded by a negativity (nerve: 140 msec, skin: 250 msec). Whereas these components were always maximal at the vertex, an earlier negativity appeared over the somatosensory projection area (nerve: 70 msec, skin: 170 msec). After stimulation of the lower limb all latencies were delayed by 20-30 msec. As a rule, the heat-evoked potentials appeared about 100 msec later than the corresponding potentials after electrical nerve stimulation. Similarities in interpeak latencies and scalp topography indicated similar cerebral processing.
Pain-related somatosensory evoked potentials (SEPs) following CO2 laser stimulation were analyzed in normal volunteers. Low power and long wavelength CO2 laser stimuli to the hand induced a sharp pain which was associated with a large positive component, P320, recorded over the scalp. Amplitude decreased and latency increased with reduction in stimulus intensity and subjective pain feeling. P320 was maximal at the vertex but was distributed widely over the scalp. There were no topographic differences between left- and right-hand stimulation, or between hand and chest stimulation. Lidocaine injection to produce anesthetic nerve block resulted in loss of P320, but the potential was relatively preserved during ischemic nerve block. No potential corresponding to P320 could be recorded following electrical or mechanical tactile stimulation. We consider P320 to be generated by impulses arising from pain stimuli and ascending through A delta fibers. We propose the thalamus as a generator source from considering its scalp topography, but pain-specific cognition or perception may also be involved in generating this potential.
Summated evoked responses to median and peroneal nerve stimulation were recorded from surface electrodes placed over the lumbar, thoracic and cervical spine of 16 normal adults. The response consisted of triphasic potentials (initially positive) which progressively increased in latency at more rostral recording sites. The conduction velocity of the response to peroneal nerve stimulation was about 65 m/sec from lumbar to cervical recording locations. However, the speed of conduction up the spine was non-linear. It was slower over caudal cord segments than over the cauda equina or rostral spinal cord. The response was greatest in amplitude and duration and sometimes complex in configuration over the lower thoracic spine overlying the area in which peroneal nerve roots enter and begin to ascend the spinal cord. In 3 patients with spinal cord lesions clinically judged to be complete, responses caudal to the lesion were similar to those recorded in normal subjects. Leads rostral to the lesion yielded no response. These findings are consistent with the interpretation that these potentials arise in the dorsal roots of the cauda equina and in spinal cord afferent pathways.
The contralateral somatosensory evoked responses to mechanical stimuli, such as pin-prick, touch and tactile tap, applied to the middle finger and to the big toe were studied in 33 normal young volunteers and in 61 patients with neurological disorders, with emphasis on the early components of the response.In normal subjects, the well-defined cortical responses to mechanical stimuli could be obtained by the method used in this study, but the consistency with which the responses could be recorded was a little lower than in the case of electrical stimulation. In each subject, the bilateral peak latencies and wave forms were almost equal, whereas the amplitudes were greatly changed over the two hemispheres.The results obtained in this study with regard to a correlation between sensory deficit and alterations in the somatosensory evoked responses to mechanical stimulation in patients with peripheral neuropathy and with cerebral lesions are in general agreement with previous investigations of the responses evoked by electrical stimulation.The findings in patients with dissociated sensory loss due to the spinal cord lesions suggest that the afferent impulses responsible for the somatosensory evoked responses to mechanical stimulation travel by the ventro-lateral tracts.
Somatosensory evoked potentials (SEPs) were elicited by stimulation of the posterior tibial nerve (PTN) in 12 normal adults. Recording using both cephalic and non-cephalic references were obtained from multiple electrodes placed over the spine and scalp. Following PTN stimulation, the fastest recorded potentials of the afferent sensory volley proceeds up the spinal cord at constant velocity. After arrival of the volley at cervical cord levels, 3 widely distributed waves, P28, P31 and N34, are recorded from scalp electrodes. These 'far-field' potentials are followed by a localized positivity (P38) which has a peak voltage either at the vertex or just laterally toward the side of stimulation. A contralateral negativity (N38) was present in most individuals. We propose that P28 arises from medial lemniscus; that P31 is generated by ventrobasal thalamus; and that N34 is probably the result of further activity in thalamus and/or thalamocortical radiations. The P38/N38 complex represents the primary cortical response to PTN stimulation. Its most consistent characteristic is a positivity at the vertex or immediately adjacent scalp areas ipsilateral to the stimulated leg. The topography of the P38/N38 potential varies slightly from individual to individual in a manner consistent with a functional dipole situated in the leg and foot area on the mesial aspect of the postcentral gyrus, whose exact location and orientation changes in accordance with known variations in the location of the leg area.
Scalp topography of somatosensory evoked potentials following mechanical (SEPs(M)) and electrical (SEPs(E)) stimulation of the left middle finger was investigated with linked ear reference in 21 normal young adults. A small plastic ball (touch) or needle (pain) was used for the mechanical stimulation. With mechanical stimulation, at least 3 positive and 3 negative potentials (P19(M), N24(M), P29(M), N36(M), P49(M) and N61(M] were found in the post-rolandic area contralateral to the stimulation. The wave form in SEPs(M) was similar to those in SEPs(E), but the peak latency of each component in SEPs(M) was 1-4 msec longer than that in SEPs(E). Earlier components such as P19(M), N24(M) and P29(M) were not as clearly recognized as corresponding components in SEPs(E). However, the wave form recorded on the hemisphere ipsilateral to the stimulation or in the frontal area contralateral to the stimulation showed a greater difference from subject to subject. P19(M), N24(M) and P29(M) correlated positively both with arm length and height of the subject. There was no significant difference of the wave form between the linked ear reference and the bipolar (C4-Fz) derivation. Wave form of SEPs(M) by needle stimulation did not significantly differ from that by plastic ball stimulation.
Minimal conduction velocities of peripheral nerves contributing to acute thermal pain sensation in human volunteer subjects were calculated. Purely thermal stimulation was administered by a low power laser beam directed at the subjects' fingers, and subjective pain responses correlated with a peak in the event-related brain potential (ERBP). These cerebral responses were found to preclude C fiber peripheral activity from this phenomenon.
Short radiant heat pulses, emitted by a high power CO2 laser, were used to investigate single nociceptor activity, cerebral potentials and concomitant sensations. Stimuli of 20 and 50 ms duration with different intensities were randomly applied to the hairy skin of the hand. Microelectroneurography was performed from the radial nerve at the wrist; 26 stable recordings were evaluated. Pre- and post-stimulus EEG segments were recorded from vertex versus linked ear lobes. Sensation was assessed on an eight-step category scale, an adjective scale, and by reaction times. In some experiments an A-fibre block was applied in order to isolate C-fibre responses. The main results were: Short heat stimuli activate C-units. In addition one of two identified A delta-units responded. None of the 15 A beta-units investigated was activated by the heat pulses. Short heat stimuli evoked cerebral potentials having a main vertex positive component at about 400 ms. These potentials were ascribed to A delta-fibre input. Laser induced pain consisted of an immediate stinging component, followed by a burning pain which often lasted several seconds. Reaction time to first pain ranged from 400-500 ms. Weak laser stimuli induced non-painful sensations mostly of tactile character. High correlations were found between the number of spikes elicited by a given stimulus and the intensity of the evoked sensation. Intensity discrimination, as evaluated by measures of Signal Detection Theory, was better in the peripheral C-units than in the subjective ratings. If conduction of A-fibres was blocked by pressure, A delta-related cerebral potential components vanished.(ABSTRACT TRUNCATED AT 250 WORDS)
In 21 normal subjects, far-field somatosensory potentials were recorded from the scalp after stimulation of the tibial nerve at the ankle (tibial SEP). With the use of a knee reference contralateral to the side of stimulation, the tibial SEP consisted of three major positive peaks, P17, P24, and P31, and three additional but inconsistent components, P11, P21, and P27. Presumable generator sources of the tibial SEP are the popliteal fossa for P11, entry to the sacral plexus for P17, the cauda equina for P21, entry to the conus medullaris for P24, the rostral spinal cord for P27, and the brainstem for P31.
Thermal (laser) evoked responses were obtained from 13 male volunteers. A single trial analysis technique with a latency adjusting adaptive filter was used to analyze evoked response amplitudes. Significant and substantial within-subject linear correlations were found between the magnitude (A) of the primary waveform (RMS muV of the P200--N300-P400 complex ) and subjective pain response (R) as well as stimulus intensity (S). Since subjective pain response was strongly correlated with stimulus intensity, the partial correlation coefficients were calculated for R vs. A with S controlled, and S vs. A with R controlled, for each subject. The partial correlations revealed a much stronger relationship between subjective response and the evoked response amplitude, suggesting that the primary complex may measure neural events in the pain perception process rather than transduction and transmission of the stimulus event.
CO 2 laser-induced pain-related somatosensory evoked potentials in peripheral neuropathies: correlation between electrophysioiogical and histopathologieal findings
- R Kakigi
- H Shibasaki
- K Tanaka
- T Lkeda
- K Oda
- C Endo
- A Ikeda
- R Neshige
- Y Kuroda
- K Miyata
- S Yi
- S Lkegawa
- S Araki
Kakigi, R., Shibasaki, H., Tanaka, K., lkeda, T., Oda, K., Endo, C., Ikeda, A., Neshige, R., Kuroda, Y., Miyata, K., Yi, S., lkegawa, S. and Araki, S. CO 2 laser-induced pain-related somatosensory evoked potentials in peripheral neuropathies: correlation between electrophysioiogical and histopathologieal findings. Muscle Nerve, 1991a, in press.