Neurogenic hyperalgesia versus painful hypoalgesia: two distinct mechanisms of neuropathic pain

Patients with sensory disturbances of painful and non-painful character show distinct changes in touch and/or pain sensitivity. The patterns of sensory changes were compared to those of human surrogate models of neuropathic pain to assess the underlying mechanisms. We investigated 30 consecutive in-patients with dysaesthesia of various origins (peripheral, spinal, and brainstem lesions) and 15 healthy subjects. Tactile thresholds were determined with calibrated von Frey hairs (1.1mm). Thresholds and stimulus-response functions for pricking pain were determined with a series of calibrated punctate mechanical stimulators (0.2mm). Allodynia was tested by light stroking with a brush, Q-tip, and cotton wisp. Perceptual wind-up was tested by trains of punctate stimuli at 0.2 or 1Hz. Intradermal injection of capsaicin (n=7) and A-fiber conduction blockade (n=8) served as human surrogate models for neurogenic hyperalgesia and partial nociceptive deafferentation, respectively. Patients without pain (18/30) showed a continuous distribution of threshold shifts in the dysaesthetic skin area with a low to moderate increase in pain threshold (by 1.52+/-0.45 log2 units). Patients with painful dysaesthesia presented as two separate groups (six patients each): one showing lowered pain thresholds (by -1.94+/-0.46 log2 units, hyperalgesia) and the other elevated pain thresholds (by 3.02+/-0.48 log2 units, hypoalgesia). The human surrogate model of neurogenic hyperalgesia revealed nearly identical leftward shifts in stimulus-response function for pricking pain as patients with spontaneous pain and hyperalgesia (by a factor of about 5 each). The sensory changes in the human surrogate model of deafferentation were similar to patients with hypoalgesia and spontaneous pain (rightward shift of the stimulus-response function with a decrease in slope). Perceptual wind-up did not differ between symptomatic and control areas. There was no exclusive association of any parameter obtained by quantitative sensory testing with a particular disease (of either peripheral or central origin). Our findings suggest that neuropathic pain is based on two distinct mechanisms: (I) central sensitization (neurogenic hyperalgesia; in patients with minor sensory impairment) and (II) partial nociceptive deafferentation (painful hypoalgesia; in patients with major sensory deficit). This distinction as previously postulated for postherpetic neuralgia, is obviously valid also for other conditions. Our findings emphasize the significance of a mechanism-based classification of neuropathic pain.     

Area-specific representation of mechanical nociceptive stimuli within SI cortex of squirrel monkeys

While functional imaging studies in humans have consistently reported activation of primary somatosensory cortex (SI) with painful stimuli, the specific roles of subdivisions of areas 3a, 3b, and 1 within SI during pain perception are largely unknown, particularly in the representation of mechanical evoked pain. In this study, we investigated how modality, location, and intensity of nociceptive stimuli are represented within SI by using high-spatial resolution optical imaging of intrinsic signals in Pentothal-anesthetized squirrel monkeys. Perceptually comparable mechanical nociceptive and innocuous tactile stimuli were delivered by indenting the glabrous skin of the distal finger pads with 0.2 and 2 mm diameter probes, respectively. Within each of areas 3a, 3b, and 1, activations to mechanical nociceptive stimulation of individual distal finger pads were spatially distinct and somatotopically organized. We observed differential cortical activation patterns. Areas 3a, 3b, and 1 were all activated during mechanical nociceptive stimulation and were modulated by nociceptive stimulus intensity. However, with innocuous tactile stimulation, mainly areas 3b and 1 exhibited response modulation with different levels of stimulation. In summary, mechanical nociceptive inputs are area-specific and topographically represented within SI. We propose that all areas of SI are implicated in encoding the features of mechanical nociception, where areas 3a and 3b are distinctively involved in coding nociceptive and pressure sensation components of stimulation.     

Secondary hyperalgesia and perceptual wind-up following intradermal injection of capsaicin in humans

Wind-up and secondary hyperalgesia both are related to central sensitization, but whereas the former is explained by homosynaptic facilitation, the latter is due to heterosynaptic facilitation. To investigate possible interactions between both types of facilitation, we tested for alterations of perceptual wind-up in the secondary hyperalgesic skin zone adjacent to a capsaicin injection with light touch (by a cotton wisp) and punctate stimuli (calibrated von Frey hairs and pin pricks). Temporal summation of pain sensation (perceptual wind-up) was only observed with a clearly noxious stimulus (pin prick) presented at a repetition frequency of 0.6 s⁻¹, but not 0.2 s⁻¹. Pain ratings to trains of pin pricks reached a plateau after 3–4 repetitions, which was 1.65 times the initial rating (`wind-up ratio'). Injection of capsaicin induced a tenderness to mechanical stimuli in adjacent uninjured skin (secondary hyperalgesia), including hyperalgesia to light touch (allodynia) and hyperalgesia to punctate stimuli. Hyperalgesia to punctate stimuli was characterized by a leftward shift of the stimulus response function, corresponding to a decrease in pain threshold and an increase of painfulness of suprathreshold stimuli by a factor of 3–4. After capsaicin, the difference between the ratings of the first and last stimuli of trains of pin pricks was increased, but the ratio was unchanged. This behavior is equivalent to an increase in effective stimulus intensity, and could be mimicked by increasing the pin prick force from 20 mN to 40 and 80 mN in normal skin. Thus, the leftward shift of the stimulus response function fully accounts for all alterations of pain sensitivity to punctate stimuli in the zone of secondary hyperalgesia. We conclude that when the gain of spinal transmission was changed in secondary hyperalgesia, the gain of wind-up remained unchanged. These findings indicate that secondary hyperalgesia (heterotopic facilitation) and wind-up of pain sensation (homotopic facilitation) are independent phenomena.     

Vestibular tactile and pain thresholds in women with vulvar vestibulitis syndrome

Vulvar vestibulitis syndrome (VVS) is a common cause of dyspareunia in pre-menopausal women. Little is known about sensory function in the vulvar vestibule, despite Kinsey's assertion that it is important for sexual sensation. We examined punctate tactile and pain thresholds to modified von Frey filaments in the genital region of women with VVS and age- and contraceptive-matched pain-free controls. Women with VVS had lower tactile and pain thresholds around the vulvar vestibule and on the labium minus than controls, and these results were reliable over time. Women with VVS also had lower tactile, punctate pain, and pressure-pain tolerance over the deltoid muscle on the upper arm, suggesting that generalized systemic hypersensitivity may contribute to VVS in some women. In testing tactile thresholds, 20% of trials were blank, and there was no group difference in the false positive rate, indicating that response bias cannot account for the lower thresholds. Women with VVS reported significantly more catastrophizing thoughts related to intercourse pain, but there was no difference between groups in catastrophizing for unrelated pains. Pain intensity ratings for stimuli above the pain threshold increased in a parallel fashion with log stimulus intensity in both groups, but the ratings of distress were substantially greater in the VVS group than in controls at equivalent levels of pain intensity. The data imply that VVS may reflect a specific pathological process in the vestibular region, superimposed on systemic hypersensitivity to tactile and pain stimuli.     

Repeated noxious stimulation of the skin enhances cutaneous pain perception of migraine patients in-between attacks: clinical evidence for continuous sub-threshold increase in membrane excitability of central trigeminovascular neurons

Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight decrease in mechanical pain thresholds, suggest that central nociceptive neurons do express activation-dependent plasticity. These findings may point to an important pathophysiological change in membrane properties of nociceptive neurons of migraine patients; a change that may hold a key to more effective prophylactic treatment.     

Is the R3 component of the human blink reflex nociceptive in origin?

The R3 component of the blink reflex can reproducibly be evoked by noxious stimulation but can probably also be elicited by innocuous stimuli. This study was conducted to investigate the contribution of nociceptive A delta and C fibers to the generation of the electrically evoked R3 blink reflex. Electrical thresholds for detection, pain and all blink reflex components were determined and the modulatory effects of local anesthesia were investigated. The electrical R3 threshold of 4.6 +/- 0.5 mA (mean +/- SE) corresponded to 2.9 times the detection threshold and to 0.35 times the pain threshold. The R3 threshold was significantly below the pain threshold. Under local anesthesia of the supraorbital skin with a complete loss of warm and cold sensation, a loss of pinprick sensation, but a normal detection of tactile stimuli, the electrical pain threshold increased, all other thresholds remained unchanged. Under local anesthesia none of the reflex components were significantly reduced. Cutaneous A beta fibers and nociceptive A delta fibers, but not unmyelinated C fibers, contribute to the generation of the electrically evoked R3 component. According to the recruitment order in peripheral sensory nerves the electrical threshold of the R3 is mainly determined by activation of A beta fibers. Thus, it can not be assumed that the electrically evoked R3 is an adequate model to investigate nociceptive processing.     

Hyperalgesia and temporal summation of pain after heat injury in man

Temporal summation of pain occurs when repeated stimuli become increasingly painful in spite of unchanged stimulus intensity. Summation can be quantified as the difference in pain between the first and the last stimulus in a train of stimuli. The aim of the study was to compare temporal summation of pain in normal skin with summation of pain in skin with primary and secondary hyperalgesia evoked by a heat injury. A heat injury was produced on the crus of 12 volunteers with a 50×25 mm thermode (47°C, 7 min). Measurements were made before, and 0, 1, 2, and 4 h after the heat injury, in three areas: primary and secondary mechanical hyperalgesia induced by the heat injury, and in a mirror image of the injury on the opposite leg. Temporal summation of pain was induced by repeated electrical stimuli (five stimuli at 2 Hz) and assessed by visual analog scale (VAS). Primary hyperalgesia was evaluated by von Frey hairs and electrical stimuli, and the areas of secondary hyperalgesia with a rigid von Frey hair (314 mN). Significant primary (P<0.000001) and secondary (P<0.00006) mechanical hyperalgesia were evoked by the heat injury. The pain threshold to single electrical stimuli was reduced within the injury (P<0.03), but not outside. The pain responses to single and repeated electrical stimuli were not significantly altered by the injury. Temporal summation of pain occurred in 418 stimulus trains out of 576 (73%), but no significant changes in summation developed in skin with primary or secondary mechanical hyperalgesia compared with normal skin (baseline measurements). Temporal summation at high stimulus intensities was more pronounced than at lower intensities (P<0.0002). We found no correlation between either temporal summation and area of secondary hyperalgesia, or temporal summation and pain intensity during the induction of heat injury. We conclude that the development of primary and secondary mechanical hyperalgesia after heat injury in man was not associated with changes in temporal summation of painful electrical stimuli.     

Innocuous skin cooling modulates perception and neurophysiological correlates of brief CO2 laser stimuli in humans.

The present study examined the influence of innocuous skin cooling on the perception and neurophysiological correlates of brief noxious CO2 laser stimuli. In nine normal subjects, brief CO2 laser pulses of four different intensities (duration 50 ms; diameter 5 mm; intensity range 5.8-10.6 mJ/mm2) were delivered at random every 5-10 s on the dorsum of the hand. Innocuous skin cooling was performed by a thermode (20 degrees C; 3x3 cm) with a central hole for the laser test stimuli. Quality and intensity (VAS) of perceptions, reaction times and laser evoked potentials (LEPs) were examined. Signal detection theory analysis was performed to evaluate discrimination performance and decision criterion. During innocuous skin cooling, detection threshold increased from 4.8+/-1.81 to 8.2+/-1.05 mJ/mm2 and pain threshold from 8.7+/-1.53 to 13.5+/-1.57 mJ/mm2. proportion of detected stimuli decreased from 87% to 48% and pain reports from 42% to 10%. The well localized 'pricking' sensation mediated by Adelta-nociceptors almost vanished. The intensity of sensations (VAS scores) was considerably reduced. Sensory discriminative performance was significantly depressed but decision criterion remained unchanged. Reaction times were delayed. The late-LEPs, correlates of Adelta-nociceptor activations, were also significantly depressed while the ultra-late LEPs, correlates of C-nociceptors, were not affected. Taken together, these results strongly suggest that innocuous skin cooling interfered with the sensory processing of laser heat stimuli and more prominently with those related to Adelta-nociceptive input.     

Localization of touch versus heat pain in the human hand: a dissociative effect of temporal parameters on discriminative capacity and decision strategy

We studied the influence of temporal parameters on localization of monofilament-evoked touch versus thulium laser-induced and C fiber-mediated pain in human subjects. Stimuli were applied at interstimulus intervals (ISIs) varying from 1 to 9 s to determine discrimination between successive stimulus sites in the palmar skin. Localization threshold was about two times higher for heat pain than touch. The localization threshold for pain, but not touch, decreased with prolongation of the ISI from 1 to 7-9 s, and it remained higher for pain even at the ISI of 9 s. The response time was longer for pain than touch, and it increased with an increase in the ISI, independent of the modality. Discriminative capacity, as assessed by the receiver operating characteristics curve, was markedly better for touch than pain. The discriminative capacity decreased with an increase of the ISI, but only for touch. The results indicate that localization is more accurate for touch than pain. Temporal summation of C fiber-evoked pain contributes to the reduced accuracy of pain localization if the ISI is < or = 3 s. Additionally, temporal factors dissociatively influence the response strategy in the tactile versus pain localization task with the prolongation of the ISI from 1 to 9 s. Due to this strategy change, localization threshold for touch remains constant at prolonged ISIs, in spite of a decrease in discriminative capacity. In a cutaneous localization task, the subject's accuracy and response strategy vary with the modality and temporal parameters of sequential test stimulation.     

Tactile discrimination, but not tactile stimulation alone, reduces chronic limb pain

Chronic pain is often associated with reduced tactile acuity. A relationship exists between pain intensity, tactile acuity and cortical reorganisation. When pain resolves, tactile function improves and cortical organisation normalises. Tactile acuity can be improved in healthy controls when tactile stimulation is associated with a behavioural objective. We hypothesised that, in patients with chronic limb pain and decreased tactile acuity, discriminating between tactile stimuli would decrease pain and increase tactile acuity, but tactile stimulation alone would not. Thirteen patients with complex regional pain syndrome (CRPS) of one limb underwent a waiting period and then 2 weeks of tactile stimulation under two conditions: stimulation alone or discrimination between stimuli according to their diameter and location. There was no change in pain (100 mm VAS) or two-point discrimination (TPD) during a no-treatment waiting period, nor during the stimulation phase (p > 0.32 for both). Pain and TPD were lower after the discrimination phase [mean (95% CI) effect size for pain VAS = 27 mm (14–40 mm) and for TPD = 5.7 mm (2.9–8.5 mm), p < 0.015 for both]. These gains were maintained at three-month follow-up. We conclude that tactile stimulation can decrease pain and increase tactile acuity when patients are required to discriminate between the type and location of tactile stimuli.     

Intravenous morphine does not modify dorsal horn touch-evoked allodynia in the mononeuropathic rat: a Fos study

In a model of mononeuropathic pain (chronic constriction injury of the sciatic nerve, CCI), we have demonstrated that light touch stimuli (stroking) to the paw induced Fos-like immunoreactivity (Fos-LI) in the superficial and deep dorsal horn of the rat spinal cord (Catheline et al., Pain 80 (1999a) 347). The efficacy of opioids in neuropathic pain being controversial, we have tested the effects of morphine (0.3, 1 and 3 mg/kg intravenous, i.v.) on this spinal Fos-LI evoked by light tactile stimuli, which could be related to mechanical allodynia. Morphine did not change the level of spinal Fos-LI observed following light touch stimuli in the CCI rats (43 +/- 3, 38 +/- 7, and 37 +/- 4 Fos-LI neurones/40 microm L4-L5 section, respectively, for the three doses versus 32 +/- 4 in the control group). In contrast, the administration of 3 mg/kg of i.v. morphine reduced by 30% the number of Fos-LI neurones induced by heat stimulation (52 degrees C, 15 s duration) in CCI rats (P < 0.05) as in sham-operated rats. These effects were reversed by the systemic administration of naloxone. The lack of effect of morphine on touch-evoked Fos-LI in the superficial dorsal horn reinforces the assertion that dynamic mechanical allodynia is related to information transmitted by A-beta fibres, since opioid receptors are mainly located on thin primary afferent fibres. Our results provide a basis for a certain form of allodynia that is insensitive to morphine.     

Differential fMRI activation to noxious heat and tactile stimuli in parasylvian areas of new world monkeys

Emerging evidence supports an important role of posterior parasylvian areas in both pain and touch processing. Whether there are separate or shared networks for these sensations remains controversial. The present study compared spatial patterns of brain activation in response to unilateral nociceptive heat (47.5°C) or innocuous tactile stimulation (8-Hz vibration) to digits through high-resolution functional magnetic resonance imaging (fMRI) in squirrel monkeys. In addition, the temporal profile of heat-stimulus-evoked fMRI Blood Oxygenation Level Dependent (BOLD) signal changes was characterized. By examining high-resolution fMRI and histological measures at both the individual and the group levels, we found that both nociceptive heat and tactile stimuli elicited activation in bilateral secondary somatosensory and ventral parietal areas (S2/PV) and in ipsilateral ventral somatosensory areas (VS) and retroinsula (Ri). Bilateral posterior insular cortex (pIns) and area 7b responded preferentially to nociceptive heat stimulation. Single voxels within each activation cluster showed robust BOLD signal changes during each block of nociceptive stimulation. Across animals (n = 11), nociceptive response magnitudes of contralateral VS and pIns and ipsilateral Ri were significantly greater than corresponding areas in the opposite hemisphere. In sum, both distinct and shared areas in regions surrounding the posterior sylvian fissure were activated in response to nociceptive and tactile inputs in nonhuman primates.     

High-resolution functional magnetic resonance imaging mapping of noxious heat and tactile activations along the central sulcus in New World monkeys

This study mapped the fine-scale functional representation of tactile and noxious heat stimuli in cortical areas around the central sulcus of anesthetized squirrel monkeys by using high-resolution blood oxygen level-dependent (BOLD) fMRI at 9.4T. Noxious heat (47.5 °C) stimulation of digits evoked multiple spatially distinct and focal BOLD activations. Consistent activations were observed in areas 3a, 3b, 1, and 2, whereas less frequent activation was present in M1. Compared with tactile activations, thermal nociceptive activations covered more area and formed multiple foci within each functional area. In general, noxious heat activations in area 3b did not colocalize with tactile responses. The spatial relationships of heat and tactile activations in areas 3a and 1/2 varied across animals. Subsequent electrophysiological mapping confirmed that the evoked heat and tactile BOLD signals were somatotopically appropriate. The magnitude and temporal profiles of the BOLD signals to noxious heat stimuli differed across cortical areas. Comparatively late-peaking but stronger signals were observed in areas 3b and 2, whereas earlier-peaking but weaker signals were observed in areas 3a, 1, and M1. In sum, this study not only confirmed the involvement of somatosensory areas of 3a, 3b, and 1, but also identified the engagements of area 2 and M1 in the processing of heat nociceptive inputs. Differential BOLD response profiles of the individual cortical areas along the central sulcus suggest that these areas play different roles in the encoding of nociceptive inputs. Thermal nociceptive and tactile inputs may be processed by different clusters of neurons in different areas.     

Psychophysical correlates in adults with sensory modulation disorder

Purpose: Individuals with sensory modulation disorder (SMD) demonstrate abnormal responses to naturally occurring stimuli in a manner that interferes with daily life activities. This study is the first study applying quantitative sensory testing to characterize the somatosensory sensitivity of adults with SMD. Method: One hundred and fifty one adults (68 males and 83 females) were tested comparing 91 SMD to 60 SMD-free, control individuals. Group placement (SMD vs. SMD-free) was determined using the Sensory Responsiveness Questionnaire (SRQ). Sensory detection thresholds for skin warming, cooling, punctate dynamic tactile sensation, vibration and thermal pain thresholds for heat and cold stimuli were determined at several body sites. Pinprick pain and prickliness were also assessed, as well as the duration and intensity of the after-sensations of prickliness and pain evoked by the prickly stimuli. Results: Compared to control adults, individuals with SMD showed significantly higher pain intensity to prickle stimuli, marginally higher pain intensity to pinprick and hypoesthesia to punctate dynamic tactile sensation at one of two sites tested. Conclusions: These results are in line with our previous study that investigated children with SMD using the same stimuli, and found similar results. We suggest a CNS involvement as the underlying mechanisms in SMD.     

Principle components analysis of pain thresholds to thermal, electrical, and mechanical stimuli suggests a predominant common source of variance

We addressed the question whether pain thresholds to different stimuli measure independent aspects of pain or one common phenomenon. In the first case, different stimuli are required to completely characterize a subject’s pain sensitivity. In the second case, different stimuli are redundant and can be used to calculate composite scores across pain modalities. We measured pain thresholds to several stimuli (heat, heat/capsaicin, cold, cold/menthol, blunt pressure, 5-Hz sine-wave electric current (0–20 mA), punctate pressure (von Frey hairs), and von Frey hairs plus capsaicin application) in 45 healthy men and 32 healthy women (aged 20–44 years). We observed that pain thresholds were significantly correlated with each other. Principal component analysis indicated that their variance was attributable more to the difference in subjects (variance estimate: 0.393) than to the difference in pain stimuli within a subject (variance estimate: −0.008). Among three principal components of the intercorrelation matrix with eigenvalues >1, the first, explaining 48% of the total variance, carried high loadings from all stimuli indicating that they shared a common source of half of their variance. Only minor variance components, each explaining <14% of the total variance, indicated a distinction of pain stimuli. There, a pattern of similarities and dissimilarities emerged agreeing with known distinct mechanisms of nociceptive responses to different stimuli. We conclude that characterizing a person as being generally stoical or complaining to any painful stimulus appears to be justified at least at pain threshold level.     

Characterization of chronic pain and somatosensory function in spinal cord injury subjects

The pathophysiology of the chronic pain following spinal cord injury (SCI) is unclear. In order to study it's underlying mechanism we characterized the neurological profile of SCI subjects with (SCIP) and without (SCINP) chronic pain. Characterization comprised of thermal threshold testing for warmth, cold and heat pain and tactile sensibility testing of touch, graphesthesia and identification of speed of movement of touch stimuli on the skin. In addition, spontaneously painful areas were mapped in SCIP and evoked pathological pain--allodynia, hyperpathia and wind-up pain evaluated for both groups. Both SCIP and SCINP showed similar reductions in both thermal and tactile sensations. In both groups thermal sensations were significantly more impaired than tactile sensations. Chronic pain was present only in skin areas below the lesion with impaired or absent temperature and heat-pain sensibilities. Conversely, all the thermally impaired skin areas in SCIP were painful while painfree areas in the same subjects were normal. In contrast, chronic pain could be found in skin areas without any impairment in tactile sensibilities. Allodynia could only be elicited in SCIP and a significantly higher incidence of pathologically evoked pain (i.e. hyperpathia and wind-up pain) was seen in the chronic pain areas compared to SCINP. We conclude that damage to the spinothalamic tract (STT) is a necessary condition for the occurrence of chronic pain following SCI. However, STT lesion is not a sufficient condition since it could also be found in SCINP. The abnormal evoked pain seen in SCIP is probably due to neuronal hyperexcitability in these subjects. The fact that apparently identical sensory impairments manifest as chronic pain and hyperexcitability in one subject but not in another implies that either genetic predisposition or subtle differences in the nature of spinal injury determine the emergence of chronic pain following SCI.     

"Gating" effects of simultaneous peripheral electrical stimulations on human secondary somatosensory cortex: a whole-head MEG study

The secondary somatosensory cortex (SII) is strongly involved in the processing of somatosensory tactile and nociceptive sensations. We investigated the effect on SII responses of simultaneous painful and nonpainful electrical stimulations delivered to the thumb and little finger. According to the "bimodal" (i.e., nociceptive, tactile) organization of SII, it was expected that simultaneous painful and nonpainful stimulations would lead to modality interference with a marked reduction ("gating") of somatosensory evoked fields (SEFs) generated in SII. Eight different stimulus conditions were studied. Two conditions were simultaneous "unimodal" (thumb and little finger nonpainful; thumb and little finger painful) and two conditions were simultaneous "bimodal" (thumb nonpainful and little finger painful; thumb painful and little finger nonpainful). As a reference, four conditions included stimulations at single sites (thumb nonpainful, little finger nonpainful, thumb painful, little finger painful). The gating phenomenon was defined as the percentage of difference between the intensities of SII activation after simultaneous compared to the sum of the separate stimulations. Results showed that simultaneous stimulations induced gating effects on SEFs generated by SII. No significant gating differences were observed after the two unimodal stimulations, suggesting a negligible effect of global energy on gating. Instead, the gating effects on bilateral SII activity were stronger after simultaneous bimodal when compared to unimodal stimulations. Our findings hint that there could be a greater level of integration/convergence of painful and nonpainful stimuli in SII with respect to SI. Future studies should explore if it could have an important role in exploring pain relief.     

Idiopathic trigeminal neuralgia: sensory features and pain mechanisms

We present a case report of a patient with the typical sensory features of idiopathic trigeminal neuralgia (ITN). The pain was elicited by innocuous stimuli, summated with repeated stimulation, radiated outside the stimulus zone, referred to a distant site, persisted beyond the period of stimulation, and exhibited a variable refractory period. Unusual sensory features included multiple trigger zones that changed over time and involved all 3 trigeminal divisions. Our sensory evaluation indicated that the pain was evoked by repetitive activation of rapidly adapting, A beta, low-threshold mechanoreceptive afferents. However, activation of such mechanoreceptive afferents alone never produces pain in normal situations and often leads to a suppression of pain responsivity. The findings support the idea that the mechanism of pain in ITN involves pathophysiological mechanisms in the central nervous system. Our hypothesis is that structural and functional changes in the trigeminal system result in an alteration in the receptive field organization of wide-dynamic-range (WDR) neurons. There appears to be an alteration in the surround inhibition mechanism of these neurons leading to an expansion of their touch receptive fields. This results in touch stimuli producing activity in WDR neurons that mimics the activity produced under normal conditions by noxious stimuli. Since WDR neurons participate in the encoding of the perceived intensity of noxious stimuli, a series of punctate tactile stimuli are now perceived as localized, pin-prick or electric shock-like sensations. Similar pathophysiological mechanisms may explain, in part, the pain of peripheral neuropathies associated with postherpetic neuralgia, diabetes and causalgia.