Vc Region Research Articles

Modulation of excitatory synaptic transmissions by TRPV1 in the spinal trigeminal subnucleus caudalis neurons of neuropathic pain rats

The present study examined contribution of the transient receptor potential vanilloid 1 channel (TRPV1) to the chronic orofacial pain. Bilateral partial nerve ligation (PNL) of the mental nerve, a branch of trigeminal nerve, was performed to induce neuropathic pain. The withdrawal threshold in response to mechanical stimulation of the lower lip skin was substantially reduced after the surgery in the PNL rats while it remained unchanged in the sham rats. This reduction in the PNL rats was alleviated by pregabalin injected intraperitoneally (10 mg/kg) and intracisternally (10, 30, 100 μg). Furthermore, an intracisternal injection of AMG9810, an antagonist of TRPV1, (1.5, 5.0 μg) attenuated the reduction of withdrawal threshold. Spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) were recorded from the spinal trigeminal subnucleus caudalis (Vc) neurons in the brainstem slice, which receive the orofacial nociceptive signals. In the PNL rats, superfusion of capsaicin (0.03, 0.1 μM) enhanced their frequency without effect on the amplitude and the highest concentration (0.3 μM) increased both the frequency and amplitude. In the sham rats, only 0.3 μM capsaicin increased their frequency. Thus, capsaicin-induced facilitation of sEPSCs and mEPSCs in the PNL rats was significantly stronger than that in the sham rats. AMG9810 (0.1 μM) attenuated the capsaicin's effect. Capsaicin was ineffective on the trigeminal tract-evoked EPSCs in the PNL and sham rats. These results suggest that the chronic orofacial pain in the PNL model results from facilitation of the spontaneous excitatory synaptic transmission in the Vc region through TRPV1 at least partly.

Japanese Rice Wine can reduce psychophysical stress-induced depression-like behaviors and Fos expression in the trigeminal subnucleus caudalis evoked by masseter muscle injury in the rats.

We determined if Japanese Rice Wine (Sake) had inhibitory effects on stress-induced enhancement of masseter muscle (MM) nociception in the rats. Male rats were subjected to the repeated forced swim stress (FS) or sham conditionings from Day -3 to -1. Daily administration of Sake or saline was conducted after each stress conditioning. At Day 0 the number of Fos positive cells, a marker for neural activity, was quantified at the trigeminal subnucleus caudalis (Vc) region by MM injury with formalin. FS increased MM-evoked Fos expression in the Vc region, which was inhibited by Sake compared to saline administration. Sake did not alter the number of Fos positive cells under sham conditions, indicating that inhibitory roles of Sake on neural activity in the Vc region were seen under FS conditions. These findings indicated that Sake had inhibitory roles on stress-induced MM nociception at the Vc region in our experimental conditions.

Experimental Study on Involvement of the Central Nervous System in Inferior Alveolar Nerve Damage-Associated Hyperalgesia of the Mental Region

Involvement of the central nervous system in sensory disturbances of the mental region occurring after inferior alveolar nerve damage was investigated using a rat model of inferior alveolar nerve damage. The rat inferior alveolar nerve was damaged by ligation with thread, and the course of behavioral changes after surgery was observed for 42days. In addition, activation of microglia and astroglia in the trigeminal spinal subnucleus caudalis (Vc) was analyzed using immunohistochemistry. c-Fos-positive cells were quantitatively evaluated to analyze the state of neuron excitement. The withdrawal threshold was significantly decreased 5days after surgery in the inferior alveolar nerve-ligated (IANL) group compared with that in the sham group and subsequently recovered over time. In addition, microglia and astroglia were activated in the Vc region 5days after surgery in the model group, and c-fos-positive cells were also significantly more frequent in the IANL group. However, no significant difference in the withdrawal threshold was seen between the IANL and sham groups on day 42, nor were any significant differences seen in the amounts of microglia, astroglia, or c-fos-positive cells. Interactions among microglia, astroglia, and neurons in the central nervous system might be involved in the progression of inferior alveolar nerve damage-associated mental hyperalgesia to a chronic state.

Inhibitory effects of fluoxetine, an antidepressant drug, on masseter muscle nociception at the trigeminal subnucleus caudalis and upper cervical spinal cord regions in a rat model of psychophysical stress.

This study aimed to determine whether psychophysical stress conditionings had facilitatory effects on masseter muscle nociception in the central nervous system via serotonergic mechanisms in rats. Two experiments were conducted to assess: (1) whether repeated forced swim stress for 3days increased the number of Fos-positive neurons evoked by masseter muscle injury due to formalin injection; and (2) whether serotonin-reuptake inhibitor, fluoxetine, administered daily after each stress conditioning, had modulatory roles on Fos expression. The number of Fos-positive cells was quantified in several areas within the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord regions (Vc areas), including the ventrolateral area of the trigeminal subnucleus interpolaris/Vc transition, and the middle or caudal portion of the Vc regions, since nociceptive neural activity in the Vc region could play critical roles in deep craniofacial nociception. We found that forced swim stress conditionings increased depression-like behaviors, which was prevented by fluoxetine. Repeated forced swim stress significantly increased Fos expression in all Vc areas compared with those of non-stressed rats, while systemic administration of fluoxetine significantly decreased Fos expression in all areas, but mainly in the caudal Vc region, in stressed rats. Fluoxetine had no effect on Fos expression in non-stressed rats. These results indicate that repeated forced swim stress conditionings increase Fos expression in the Vc areas, and the contribution of serotonergic mechanisms to masseter muscle nociception could be greater in stressed rats than in sham rats. These results support the hypothesis that changes in brain function, including serotonergic mechanisms, in the Vc areas play critical roles in enhanced masseter muscle nociceptive responses under psychophysical stress conditions.

Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice.

Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.

Central antinociceptive activity of peripherally applied botulinum toxin type A in lab rat model of trigeminal neuralgia.

BackgroundBoNT-A is often used in the clinical treatment for movement disorders. In recent years, various clinical studies suggest that BoNT-A can effectively alleviate pain caused by trigeminal neuralgia (TN); however, its mechanism remains unclear.MethodsIn this study, we used a lab rat model for TN produced by chronic constriction injury of the infraorbital nerve (ION-CCI). Restrained rats were injected subcutaneously with BoNT-A into the whisker pad tissue (ipsilaterally to the nerve injury) 14 days after the ION-CCI. Allodynia was tested by Von Frey filaments and TRPs and cSNAP-25 were tested by western blot.ResultsPeripheral application of BoNT-A (3, 10 U/kg) significantly increased the pain threshold of ION-CCI rats. Rota-rod test showed that BoNT-A administration at doses tested did not significantly affect rat motor coordination. By probing for a specific marker for BoNT-A, cleaved synaptosomal-associated protein 25 (cSNAP-25), we found that peripheral application of BoNT-A (10 U/kg) affected brainstem Vc, which could be blocked by the axonal transport blocker colchicine. In addition, western blot analysis showed that in the Vc region of ION-CCI rats, the expression levels of TRPA1, TRPV1, TRPV2 and TRPM8 increased, whereas peripheral application of BoNT-A significantly lowered the high expression of TRPA1, TRPV1 and TRPV2, but not TRPM8 at 7 days after BoNT-A injection.ConclusionsThe finding of this study suggest that peripherally applied BoNT-A can produce antinociceptive effects in ION-CCI model. The underlying mechanisms may be BoNT-A acts on the Vc via axonal transport, inhibits the high expression of TRPA1, TRPV1 and TRPV2, and reduces central sensitization.

Effects of prostaglandin E2 on synaptic transmission in the rat spinal trigeminal subnucleus caudalis

The spinal trigeminal subnucleus caudalis (Vc) receives preferentially nociceptive afferent signals from the orofacial area. Nociceptive stimuli to the orofacial area induce cyclooxygenase both peripherally and centrally, which can synthesize a major prostanoid prostaglandin E2 (PGE2) that implicates in diverse physiological functions. To clarify the roles of centrally-synthesized PGE2 in nociception, effects of exogenous PGE2 on synaptic transmission in the Vc neurons were investigated in the rat brainstem slice. Spontaneously occurring excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) were recorded, respectively, under pharmacological blockade of inhibitory and excitatory transmission by whole-cell patch-clamp mode. Perfusion of PGE2 (1–5μM) increased the frequency of sIPSCs in a concentration-dependent manner but had no significant effect on the amplitude. Similarly to the effects on sIPSCs, PGE2 increased the sEPSC frequency without any effect on the amplitude. These facilitatory effects of PGE2 on spontaneous synaptic transmissions were blocked by an EP1 antagonist SC19220 but not by an EP4 antagonist AH23848. Electrical stimulation of the trigeminal tract evoked short latency EPSCs (eEPSCs) in the Vc neurons. PGE2 (5μM) was ineffective on the eEPSCs. The present study demonstrated that PGE2 facilitated spontaneous synaptic transmissions in the Vc neurons through activating the presynaptic EP1 receptors but had no effect on the trigeminal tract-mediated excitatory transmission. These results suggest that centrally-synthesized PGE2 modifies the synaptic transmission in the Vc region, thereby contributing to the processing of nociceptive signals originated from the orofacial area.

Higher harmonics generation in relativistic electron beam with virtual cathode

The study of the microwave generation regimes with intense higher harmonics taking place in a high-power vircator consisting of a relativistic electron beam with a virtual cathode has been made. The characteristics of these regimes, in particular, the typical spectra and their variations with the change of the system parameters (beam current, the induction of external magnetic field) as well as physical processes occurring in the system have been analyzed by means of 3D electromagnetic simulation. It has been shown that the system under study demonstrates the tendency to the sufficient growth of the amplitudes of higher harmonics in the spectrum of current oscillations in the VC region with the increase of beam current. The obtained results allow us to consider virtual cathode oscillators as promising high power mmw-to-THz sources.

Locally released small (non‐protein) ninhydrin‐reacting molecules underlie developmental differences of cultured medullary versus spinal dorsal horn neurons

Neurons located in the trigeminal subnucleus caudalis (Vc) play crucial roles in pain and sensorimotor functions in the orofacial region. Because of many anatomical and functional similarities with the spinal dorsal horn (SDH), Vc has been termed the medullary dorsal horn--analogous to the SDH. Here, we report that when compared with embryonic SDH neurons in culture, neurons isolated from the Vc region showed significantly slower growth, lower glutamate receptor activity, and more cells undergoing cell death. SDH neuron development was inhibited in co-cultures of SDH and Vc tissues while Vc neuron development was promoted by co-culture with SDH tissues. Furthermore, we identified that small (non-protein) ninhydrin-reacting molecules purified from either embryonic or post-natal Vc-conditioned medium inhibited neuronal growth whereas ninhydrin-reacting molecules from SDH-conditioned medium promoted neuronal growth. These findings suggest the involvement of locally released factors in the region-specific regulation of neuronal development in Vc and SDH, central nervous system regions playing critical roles in pain, and point to novel avenues for investigating central nervous system regionalization and for designing therapeutic approaches to manage neurodegenerative diseases and pain.

Central Sensitization Induced in Trigeminal and Upper Cervical Dorsal Horn Neurons by Noxious Stimulation of Deep Cervical Paraspinal Tissues in Rats With Minimal Surgical Trauma

Objective This study investigated if central sensitization is induced in the trigeminal subnucleus caudalis (also termed the medullary dorsal horn) and C1 and C2 dorsal horns by noxious stimulation of deep upper cervical paraspinal tissues in a preparation relatively free of surgical trauma. Methods Adult male Sprague-Dawley rats (275-450 g) were anesthetized intraperitoneally. Animals were then placed in a stereotaxic frame; a small cutaneous incision was made 3 to 4 mm near the bregma in the midline, and an opening into the skull was prepared by a 1/32-inch drill, 1 mm to the left from the midline. An epoxylite-coated tungsten microelectrode was introduced at an 18° angle to enter this small opening on the skull and was then carefully advanced about 16 mm through cortex, cerebellum, and brainstem to reach subsequently histologically confirmed sites in the Vc and upper cervical (C1 and C2) dorsal horn region. Thirty-three, 27, and 15 neurons recorded in medullary, C1, and C2 dorsal horns, respectively, of chloralose/urethane-anesthetized rats were activated by noxious stimulation of mechanoreceptive fields involving V1, V2, and/or V3 trigeminal nerve territories. The inflammatory irritant mustard oil was injected into the deep paraspinal tissues at the level of the left C1-C2 joint. Pre and postinjection receptive field (RF) sizes were mapped by nonnoxious mechanical stimuli and noxious mechanical and heat stimuli. Results A 30- to 50-minute increase (mean, 165% ± 38.1%) in RF size postinjection for 62% of neurons tested was demonstrated, suggesting central sensitization; for most (>70%) neurons, the RF expanded caudally into cervically innervated tissues. Conclusions These findings provide the first documentation that deep cervical nociceptive inputs can induce central sensitization in medullary and C1/C2 dorsal horns and suggest that these effects may reflect mechanisms contributing to deep cervical pain and its referral.

Surface structure and composition of the missing-row reconstruction of VC 0.8(1 1 0): A LEED, GIXRD and photoemission study

Low energy electron diffraction, grazing incidence X-ray diffraction and photoemission were used to decipher the detailed structural arrangement and chemical composition of the surface region of a transition metal carbide, VC 0.8(1 1 0). In agreement with previous scanning tunneling microscopy (STM) studies, we find that the surface reconstructs with a ridge-and-valley grating structure along the [ 1 1 ¯ 0 ] direction resulting from {0 0 1} faceting for the (3 × 1) and the (4 × 1) phases. Both superstructures terminate on the vacuum side with a nearly stoïchiometric VC region due to C segregation, in contrast with the conclusions drawn from this previous STM study. However, the present experiments clearly show that these phases are metastable, and slow cooling results in a (1 × 1) surface, which is highly C depleted, similarly to the (1 0 0) face.

Microstimulation in the region of the human thalamic principal somatic sensory nucleus evokes sensations like those of mechanical stimulation and movement.

We explored the region of human thalamic somatic sensory nucleus (ventral caudal, Vc), corresponding to monkey ventral posterior (VP), with threshold microstimulation (TMIS) during stereotactic procedures for the treatment of tremor. Of 122 sites in 116 patients (124 thalami) where mechanical (touch, pressure, and sharp) or movement [movement through the body (movement) and vibration] sensations were evoked, 72 sites were found in the core or in adjacent regions, posterior-inferior (33), inferior (4), and posterior to the core (13). Sites where TMIS evoked touch were less frequently found in the core than those where movement or pressure sensations were evoked. Pressure was more commonly (P < 0.05) evoked than vibration at sites where cells had intraoral receptive fields (RFs). Touch and vibration were more commonly (P < 0.05) evoked than pressure at sites where cells had facial RFs, consistent with the relative density of rapidly adapting (RA) receptors in the mouth and face. Sites described as deep and movement were found superior and anterior in the core, consistent with the location of cells responding to stimulation of muscle afferents. At 72 of 122 sites, TMIS evoked the same sensation at two or more sites in the same plane. Of these sites, 58 are adjacent to each other, in a cluster, consistent with studies of the localization of cells responding to different modalities. These results demonstrate that mechanical and movement sensations can be evoked by stimulation in the region of Vc. The characteristics of these sites suggest that the sensations are evoked by stimulation of pathways specific to cutaneous and deep mechanoreceptors.

Medial Lateral Extent of Thermal and Pain Sensations Evoked By Microstimulation in Somatic Sensory Nuclei of Human Thalamus

We explored the region of human thalamic somatic sensory nucleus (ventral caudal, Vc) with threshold microstimulation during stereotactic procedures for the treatment of tremor (124 thalami, 116 patients). Warm sensations were evoked more frequently in the posterior region than in the core. Proportion of sites where microstimulation evoked cool and pain sensations was not different between the core and the posterior region. In the core, sites where both thermal and pain sensations were evoked were distributed similarly in the medial two planes and the lateral plane. In the posterior region, however, warm sensations were evoked more frequently in the lateral plane (10.8%) than in the medial planes (3.9%). No mediolateral difference was found for sites where pain and cool sensations were evoked. The presence of sites where stimulation evoked taste or where receptive and projected fields were located on the pharynx were used as landmarks of a plane located as medial as the posterior part of the ventral medial nucleus (VMpo). Microstimulation in this plane evoked cool, warm, and pain sensations. The results suggest that thermal and pain sensations are processed in the region of Vc as far medial as VMpo. Thermal and pain sensations seem to be mediated by neural elements in a region likely including the core of Vc, VMpo, and other nuclei posterior and inferior to Vc.

Activation of neurons in trigeminal caudalis by noxious oral acidic or salt stimuli is not reduced by amiloride

We investigated the possible role of amiloride-sensitive ion channels of the ENaC/DEGenerin superfamily in the activation of trigeminal nociceptive neurons elicited by noxious chemical stimulation of the oral mucosa using two methodologies, single-unit recording and c-fos immunohistochemistry. In pentobarbital-anesthetized rats, single-unit recordings were made from neurons in superficial laminae of dorsomedial trigeminal subnucleus caudalis (Vc) that responded to noxious thermal and chemical stimuli applied to the dorsal tongue. Successive application of each of three chemicals (250 mM pentanoic acid, n=6 units; 250 mM citric acid, n=8; 5 M NaCl, n=6) evoked responses that were not affected following topical application of amiloride (1 mM). In separate experiments, pentobarbital-anesthetized rats received one of the following stimuli delivered to the dorsal tongue: 250 mM pentanoic acid ( n=6); 1 mM amiloride followed by 250 mM pentanoic ( N=6); 5 M NaCl ( n=5); or 1 mM amiloride followed by 5 M NaCl ( n=5). Two hours later they were perfused with 4% paraformaldehyde and the brain stems processed for c-fos immunoreactivity. Both pentanoic acid and 5 M NaCl evoked similar numbers and patterns of fos-like immunoreactivity (FLI) in dorsomedial Vc and other brain stem regions, with no significant difference in counts of FLI in animals pretreated with amiloride. These results suggest that amiloride-sensitive Na + channels are not essential in mediating the activation of intraoral trigeminal nociceptors.

The effect of fentanyl on c-fos expression in the trigeminal brainstem complex produced by pulpal heat stimulation in the ferret

We have previously shown that Fos-like immunoreactivity (Fos-LI) is evoked in the brainstem of ferrets following stimulation of pulpal A δ and C fibers originating from the maxillary canine. This study evaluated the effects of the μ-opioid receptor agonist fentanyl on Fos expression evoked by noxious thermal stimulation of the right maxillary and mandibular canines in pentobarbital/chloral hydrate anesthetized adult male ferrets. Pulpal heating evoked Fos expression in two distinct regions of the spinal trigeminal nuclear complex: the transitional region between subnucleus interpolaris and caudalis (Vi/Vc) and within the subnucleus caudalis (Vc). More Fos positive cells were expressed in both regions ipsilateral to the site of stimulation compared with the contralateral side ( P<0.05, ANOVA). Pretreatment with fentanyl significantly and dose-dependently suppressed the number of Fos positive cells in both the Vi/Vc transitional region and Vc ( P<0.05, ANOVA). The suppressive effect of fentanyl on Fos expression was blocked by the intravenous administration of naloxone, an opioid antagonist, indicating a specific opioid receptor effect. In addition, opioid receptor antagonism with naloxone alone enhanced Fos expression in Vi/Vc and Vc in response to heat stimulation. The administration of naloxone without heat stimulation failed to evoke Fos expression in Vi/Vc and Vc. These findings suggest that the activation of trigeminal Vi/Vc and Vc neurons by noxious dental heat stimulation is controlled by a naloxone sensitive endogenous opioid system as indicated by Fos expression. Collectively, these results suggest that neuronal populations in Vi/Vc and Vc regions may contribute to pain responses to noxious dental stimulation and these responses can be modulated by both endogenous and exogenous opioids.

Reorganization of sensory modalities evoked by microstimulation in region of the thalamic principal sensory nucleus in patients with pain due to nervous system injury

Stimulation of the somatosensory system is more likely to evoke pain in patients with chronic pain after nervous system injury than in patients without somatosensory abnormalities. We now describe results of stimulation through a microelectrode at microampere thresholds (threshold microstimulation; TMIS) in the region of the human thalamic principal sensory nucleus (ventral caudal; Vc) during operations for treatment of movement disorders or of chronic pain. Patients were trained preoperatively to use a standard questionnaire to describe the location (projected field) and quality of sensations evoked by TMIS intraoperatively. The region of Vc was divided on the basis of projected fields into areas representing the part of the body where the patients experienced chronic pain (pain affected) or did not experience chronic pain (pain unaffected) and into a control area located in the thalamus of patients with movement disorders and no experience of chronic pain. The region of the Vc was also divided into a core region and a posterior-inferior region. The core was defined as the region above a standard radiologic horizontal line (anterior commissure-posterior commisure line; ACPC line) where the majority of cells responded to innocuous somatosensory stimulation. The posterior-inferior area was a cellular area posterior and inferior to the core. In both the core and the posterior-inferior regions, the proportion of sites where TMIS evoked pain was larger in pain-affected and unaffected areas than in control areas. The number of sites where thermal (warm or cold) sensations were evoked was correspondingly smaller, so that the total of pain-plus-thermal (sensation of warmth or cold) sites was the same in all areas. Therefore, sites pain where stimulation evoked pain in patients with neuropathic pain (i.e., pain following an injury to the nervous system) may correspond to sites where thermal sensations were evoked by stimulation in patients without somatosensory abnormality. J. Comp. Neurol. 399:125–138, 1998. © 1998 Wiley-Liss, Inc.

Reorganization of sensory modalities evoked by microstimulation in region of the thalamic principal sensory nucleus in patients with pain due to nervous system injury

Stimulation of the somatosensory system is more likely to evoke pain in patients with chronic pain after nervous system injury than in patients without somatosensory abnormalities. We now describe results of stimulation through a microelectrode at microampere thresholds (threshold microstimulation; TMIS) in the region of the human thalamic principal sensory nucleus (ventral caudal; Vc) during operations for treatment of movement disorders or of chronic pain. Patients were trained preoperatively to use a standard questionnaire to describe the location (projected field) and quality of sensations evoked by TMIS intraoperatively. The region of Vc was divided on the basis of projected fields into areas representing the part of the body where the patients experienced chronic pain (pain affected) or did not experience chronic pain (pain unaffected) and into a control area located in the thalamus of patients with movement disorders and no experience of chronic pain. The region of the Vc was also divided into a core region and a posterior-inferior region. The core was defined as the region above a standard radiologic horizontal line (anterior commissure-posterior commissure line; ACPC line) where the majority of cells responded to innocuous somatosensory stimulation. The posterior-inferior area was a cellular area posterior and inferior to the core. In both the core and the posterior-inferior regions, the proportion of sites where TMIS evoked pain was larger in pain-affected and unaffected areas than in control areas. The number of sites where thermal (warm or cold) sensations were evoked was correspondingly smaller, so that the total of pain-plus-thermal (sensation of warmth or cold) sites was the same in all areas. Therefore, sites pain where stimulation evoked pain in patients with neuropathic pain (i.e., pain following an injury to the nervous system) may correspond to sites where thermal sensations were evoked by stimulation in patients without somatosensory abnormality.

Thalamic stimulation-evoked sensations in chronic pain patients and in nonpain (movement disorder) patients

1. Little is known about the effect of central and peripheral nervous system injury on the processing of somatosensory information at the thalamic level in humans. The role of the human thalamic ventrocaudal nucleus (Vc) in nociception is not well understood because reports of nociceptive neuronal responses and stimulation-evoked pain are rare. In this study, we have characterized effects of microstimulation in the tactile region of Vc. Specifically, we investigated the incidence of painful sensations evoked by thalamic microstimulation in patients with and without chronic pain. 2. Data were obtained during stereotactic thalamic procedures for relief of pain or motor disorders. Patients were divided into three groups, those with 1) central poststroke pain (PSP, n = 13); 2) nonstroke pain (NSP, n = 23); and 3) movement disorders (controls, n = 24). Most (15 of 23) of the NSP patients had peripheral nerve damage. Tungsten microelectrodes were used to record neuronal responses in the thalamus and to deliver stimuli. Localization of tactile Vc was determined according to stereotactic coordinates and neuronal responses to innocuous somatic stimuli. At selected sites, microstimulation (1-s trains, 300 Hz, 0.1-0.2 ms pulses, < 100 microA) was performed and the patient was requested to describe the quality of the sensation and its peripheral location (projected field, PF). 3. Microstimulation in tactile Vc commonly evoked paresthesia-type sensations. Threshold stimulation never evoked pain in the NSP patients and evoked pain at only 2% of Vc sites in the movement disorder patients. In these latter 2 groups of patients, stimulation at > 98% of Vc sites evoked paresthesia. By contrast, in the PSP patients, 28% of Vc sites stimulated evoked painful sensations at threshold. Suprathreshold stimuli evoked painful sensations at 46% of Vc sites in the PSP patients but at only 8% of Vc sites in NSP patients and 12% of Vc sites in the movement disorder patients. 4. The thresholds to evoke paresthesia in the NSP and movement disorder patients were significantly lower than the thresholds in the PSP patients. However, stimulation thresholds to elicit pain were similar in all patient groups. 5. All patients were capable of differentiating stimulation-evoked paresthesia from pain. Stimulation-evoked painful sensations in the PSP patients were often described as burning and sometimes as "sharp," "shocking," or "unpleasant." By contrast, the quality of pain evoked in the other patient groups was typically described as unpleasant or shocking. Pain could be evoked at sites throughout tactile Vc, although most sites were located in the ventral 2/3 of the nucleus. 6. In the movement disorder patients, the location of the projected sensation usually corresponded to the location of the receptive fields of the tactile neurons recorded at the same site. By contrast, in both groups of pain patients there was a high incidence of mismatches between the projected and receptive fields. 7. These results suggest that the effective thalamic output from Vc to the cortex is affected by somatosensory deafferentation in pain patients. In addition, in the PSP patients there are also changes in the thalamocortical processing of noxious information. The increased incidence of thalamic-evoked pain in PSP patients may be due to 1) loss of low-threshold mechanoreceptive thalamic neurons such that nociceptive neuronal output is now prominent, 2) reduced tonic inhibition of thalamic or cortical nociceptive neurons, and/or 3) unmasking or strengthening of nociceptive pathways.

Characteristics of somatotopic organization and spontaneous neuronal activity in the region of the thalamic principal sensory nucleus in patients with spinal cord transection.

1. We explored the region of the principal sensory nucleus of thalamus (Vc) during stereotactic surgical procedures for treatment of patients with pain after spinal cord transection (n = 23). Receptive fields (RFs) of thalamic single neurons and locations of sensations evoked by stimulation (projected field, PF) were determined by standard methods. The cellular thalamic region where sensations were evoked at < 25 microA was termed the "region of Vc." The region of Vc in spinal patients was subdivided into different areas according to RF and PF locations. Areas that were distant from the representation of the anesthetic part of the body were termed "spinal control" areas, whereas those that were adjacent to or included in the representation of the area of absolute sensory loss were termed "border zone/anesthetic" areas. The region of Vc in movement disorder patients were termed the "control" area. 2. Border zone/anesthetic areas of thalamus often exhibited increased representations of the border of the anesthetic part of the body in comparison with the representation of the same parts of the body in control and spinal control areas. 3. In control and spinal control areas the locations of RFs and PFs were usually well matched. However, in border zone/anesthetic areas of the thalamus there was frequently a mismatch between the location of RFs and PFs (RF/PF mismatch). In border zone/anesthetic areas, RFs were often located on the border of the anesthetic part of the body whereas PFs were referred to anesthetic parts of the body. 4. Analysis of first- and higher-order properties of spontaneous neuronal activity revealed that spike trains could be classified into two groups with distinct patterns of activity. The R group (n = 49) was characterized by independence of sequential interspike intervals (ISIs), a Poisson distribution of ISIs, initially inhibitory or flat autocovariance function (acvf), and low level of high-frequency bursting. The O group (n = 26) was characterized by correlation of sequential ISIs, large sustained postspike facilitation on the acvf, and high prevalence of high-frequency bursting--all consistent with a bursting pattern of activity. A third group of spike trains (n = 17) had an initially inhibitory or flat acvf and a unimodal, positively shifted, ISI distribution that did not meet criteria for a Poisson distribution. 5. Spike trains in the R group were much more common in control and control spinal areas, whereas those in the O group were more common in border zone/anesthetic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Neurons in the area of human thalamic nucleus ventralis caudalis respond to painful heat stimuli

A population of neurons in the area of human thalamic nucleus ventralis caudalis (Vc) respond to noxious heat stimuli. In the cutaneous core of Vc 6% (6/108) of recorded neurons had a significantly greater response to noxious eat stimuli than to innocuous control stimuli. Half of these neurons ( n = 3) also responded to innocuous cold stimuli. Within the region posterior and inferior to the cutaneous core of Vc 5% (4/77) of neurons responded exclusively to noxious heat stimuli. Cells responding to noxious heat were recorded at a greater proportion (66%) of sites where painful sensations were evoked by microstimulation than at sites where nonpainful sensations were evoked (1.5%). The results suggests that neurons in the region of human Vc mediate the sensory aspect of pain.