Neurophysiological, pharmacological and behavioral evidence for medial thalamic mediation of cocaine-induced dopaminergic analgesia.

These studies examined the effects of cocaine on thalamic neurons that respond maximally either to noxious or to innocuous somatic stimulation. Cocaine attenuated high intensity electrically-evoked nociceptive responses of all 25 units studied in the parafascicular and central lateral nuclei of the medial thalamus. A dose of 1 mg/kg intravenously (i.v.) suppressed medial thalamic unit discharge evoked by both noxious somatic stimulation (49.4 +/- 8.7% of control response) and spinal cord stimulation (76.2 +/- 6.6% of control response). The effect of cocaine on unit responses to noxious somatic stimulation was dose-related in the range of 0.3-3.5 mg/kg i.v. and was attenuated by eticlopride, a D-2 selective dopamine receptor antagonist. Morphine also suppressed noxious somatic evoked responses of medial thalamic units in a dose-dependent manner. Units in the lateral (ventrobasal) thalamus (n = 4) that responded only to innocuous stimuli were not affected by cocaine at doses up to 3.5 mg/kg i.v. Ibotenic acid lesions in the parafascicular nucleus of the medial thalamus attenuated the analgesic effect of cocaine in the formalin test. These results suggest that both cocaine and the parafascicular nucleus interact with dopaminergic mechanisms that attenuate nociceptive spinal projections to the medial thalamus.     

Periaqueductal gray inhibition of trigeminal subnucleus caudalis unitary responses evoked by dentine and nonnoxious facial stimulation

The possible pain inhibitory effects of periaqueductal gray (PAG) stimulation were investigated in cats anesthetized with Nembutal and immobilized with Flaxedil. Unitary responses evoked by electrical stimulation of the upper canine dentine and by cutaneous facial noxious and nonnoxious stimuli were recorded extracellularly from the trigeminal subnucleus caudalis. A bipolar electrode was introduced into the PAG to test the effects of PAG excitation on the trigeminal response to dentine (TRED) and cutaneous nonnoxious stimulation. In some experiments, a similar electrode was lowered into the contralateral posterior thalamus to study the antidromic activation of subnucleus caudalis cells and the effects of thalamic stimulation on the TRED. Dentine stimulation evoked brief (6- to 15-ms) bursts of 1 to 10 spikes with 3- to 25-ms latencies. Most units (88%) were also activated by cutaneous facial stimulation. Stimulation of the posterior thalamus had no effect on the TRED or on responses to cutaneous stimulation, but activated antidromically 10% of the units. In 71% of the units PAG stimulation inhibited the TRED. In some of those cases (12%), the inhibitory effect persisted 30- to 60 s. The PAG stimulation could produce paradoxical effects, potentiating the TRED evoked by threshold intensity and inhibiting the TRED elicited by suprathreshold stimulation. About one-half the PAG points evoked detectable effects. Their location had no clear topographical distribution, although ventral sites were more potent than dorsal sites. Responses evoked by nonnoxious facial stimulation were also inhibited by the PAG.     

Long-term potentiation phenomena in the rat limbic forebrain

These experiments investigated the role of a specific thalamic nucleus in the cellular response to noxious and non-noxious inputs. Single-unit extracellular responses to peripheral noxious stimuli were recorded with glass micropipettes in the nucleus parafascicularis (Pf) of the rat under chloral hydrate anesthesia. Bipolar stimmulating/recording electrodes were inserted in the nucleus ventro-posterolateralis (VPL) of the thalamus, in areas responsive to the peripheral noxious stimulation. Single-unit records in Pf and multi-unit records in VPL demonstrated that both these nuclei are differentially sensitive to noxious and non-noxious inputs: Pf was more sensitive to late (200–600 ms latency) high threshold noxious inputs, while VPL was more responsive to early (10–40 ms) low threshold non-noxious inputs. Late, high threshold inputs to VPL were selectively suppressed by systemic morphine and restored by naloxone. Trains of stimuli applied to VPL suppressed the response of 76% of Pf units, to peripheral noxious stimuli but did not inhibit the response of spinal cord dorsal horn units to the same stimuli. This inhibitory effect of VPL on Pf cells was not reversed by systemically administered naloxone. The neural pathways responsible for the VPL suppression of Pf nociception appear to be neither monosynaptic nor mediated through the spinal cord dorsal horn, nor through any single, naloxone-reversible, central opioid process. Nevertheless, this inhibitory effect of VPL stimulation on Pf nociception provides a physiological basis for the analgesic effects of thalamic stimulation on clinically observed deafferentation pain. It also supports the existence of a pain modulating system at the thalamic level comparable, at least in part, with the spinal Gate Control concept.     

Thalamic nucleus ventro-postero-lateralis inhibits nucleus Parafascicularis response to noxious stimuli through a non-opioid pathway

These experiments investigated the role of a specific thalamic nucleus in the cellular response to noxious and non-noxious inputs. Single-unit extracellular responses to peripheral noxious stimuli were recorded with glass micropipettes in the nucleus parafascicularis (Pf) of the rat under chloral hydrate anesthesia. Bipolar stimmulating/recording electrodes were inserted in the nucleus ventro-posterolateralis (VPL) of the thalamus, in areas responsive to the peripheral noxious stimulation. Single-unit records in Pf and multi-unit records in VPL demonstrated that both these nuclei are differentially sensitive to noxious and non-noxious inputs: Pf was more sensitive to late (200–600 ms latency) high threshold noxious inputs, while VPL was more responsive to early (10–40 ms) low threshold non-noxious inputs. Late, high threshold inputs to VPL were selectively suppressed by systemic morphine and restored by naloxone. Trains of stimuli applied to VPL suppressed the response of 76% of Pf units, to peripheral noxious stimuli but did not inhibit the response of spinal cord dorsal horn units to the same stimuli. This inhibitory effect of VPL on Pf cells was not reversed by systemically administered naloxone. The neural pathways responsible for the VPL suppression of Pf nociception appear to be neither monosynaptic nor mediated through the spinal cord dorsal horn, nor through any single, naloxone-reversible, central opioid process. Nevertheless, this inhibitory effect of VPL stimulation on Pf nociception provides a physiological basis for the analgesic effects of thalamic stimulation on clinically observed deafferentation pain. It also supports the existence of a pain modulating system at the thalamic level comparable, at least in part, with the spinal Gate Control concept.     

Diencephalic modulation of activities of raphe-spinal neurons in the cat

The modulatory effects of diencephalic stimulation on the activities of raphe-spinal neurons were studied extracellularly in cats. Among 240 raphe neurons recorded, 57 neurons were activated antidromically by stimulation of the cervical dorsolateral funiculus. These raphe-spinal neurons were found in the caudal raphe nuclei, i.e., the raphe magnus (43 neurons), raphe obscurus (11), raphe pallidus (2), and raphe pontis (1). All of them responded to innocuous and/or noxious peripheral mechanical stimuli with a broad receptive field. The activities of the majority of these neurons were facilitated by trains of pulse stimulation of the rostral periaqueductal gray and the thalamic relay nucleus but not of the thalamic center median nucleus. The facilitation of firing persisted for more than 3 min after the cessation of train pulse stimulation when the stimulation was applied at 20 Hz for 5 to 30 s. This facilitation was not affected by decortication of the sensorimotor area bilaterally. The facilitatory response to periaqueductal gray stimulation was markedly suppressed by systemic administration of naloxone. On the other hand, that of the thalamic relay nucleus stimulation was found to be unaffected. Based on these findings, the mechanisms of pain relief by stimulation of the rostral periaqueductal gray and thalamic relay nucleus reported in human intractable pain appear to relate, at least partly, to the activation of raphe-spinal neurons. However, the paths to raphe-spinal neurons of stimuli from the periaqueductal gray and the thalamic relay nucleus are thought to be independent from each other based on the different effects of naloxone.     

Dorsal raphe and external electrical stimulation modulate noxious input to single neurons in nucleus parafascicularis thalami

Spontaneous discharges and nociceptive responses of 47 parafascicularis thalami (PF) neurons were recorded extracellularly and comparisons were made between the effects of these discharges following focal dorsal raphe stimulation (DRS) and bilateral pinnal electrical stimulation (PES). Eighty-three percent of PF neurons (N = 39) responded to noxious stimulus, about 69% of the PF responsive cells (N = 27) were excited during noxious stimuli and thus categorized as "nociceptive-on" cells. The remaining 31% (N = 12) were suppressed by the noxious stimuli, and were categorized as "nociceptive-off" cells. DRS and PES attenuated the spontaneous activity of the "nociceptive-on" neurons as well as the noxious input to these cells, while the spontaneous activity of the "nociceptive-off" cells was suppressed only following DRS and not following PES. Moreover, PES displayed disinhibiting properties, namely, it reduced the suppression effects elicited by noxious input. In conclusion, it was demonstrated that both focal DRS and noninvasive PES were effective in modulating pain input to single neurons in the PF.     

Periaqueductal gray and cerebral cortex modulate responses of medial thalamic neurons to noxious stimulation

The response of medial thalamic neurons to noxious peripheral stimulation were studied with intracellular recording methods in the cat. Electrical stimulation of the contralateral forepaw produced an EPSP-IPSP sequence followed by rebound excitation in these medial thalamic neurons. Action potentials appeared with the initial EPSP or with the rebound excitation. The mean latency to onset was 15 ms for the EPSP and 33 ms for IPSP. In contrast, electrical stimulation of the PAG or of the pericruciate cerebral cortex produced large IPSPs in the medial thalamic neurons. When PAG or cortex stimulation were paired with noxious stimulation, both the PAG and cortex responses predominated over the noxious response. This shows that the PAG and the cerebral cortex have the capabilities of influencing the responses of the medial thalamus to noxious stimulation. The medial thalamus is part of the relay system which sends information about noxious stimulation to the cerebral cortex where the noxious information reaches conscious awareness, so influencing the message at the level of the medial thalamus would probably alter the conscious perception of pain. The data suggest the existence of an ascending pain modulation system from the midbrain to the thalamus and also suggests a mechanism of cortical control over pain perception.     

Medial thalamic permanent electrodes for pain control in man: an electrophysiological and clinical study.

In 7 patients with medial thalamic electrodes implanted for relief of chronic pain, clinical observations and electrophysiological recordings showed: (1) Clinically, paresthesia in the pain area and contralateral half of the body was reported as well as some unpleasant side effects. The EEG was not changed during medial thalamic stimulation. (2) Threshold for non-painful and painful perception of electrical stimuli were not significantly raised by contralateral medial thalamic stimulation. (3) After electrical median nerve stimulation, evoked thalamic potentials started after 17 msec. With ipsilateral stimulation the early components (up to 40 msec) showed longer latencies and the late components slightly shorter latencies as compared to the contralateral stimulation. (4) Median nerve evoked cortical SSEPs are not significantly changed either by a 500 msec lasting conditioning stimulation of the dorsal columns or by such stimulation of the medial thalamic structures. A facilitation at about 90 msec was found in the cortical SSEP after medial thalamic conditioning in only one of three patients tested. (5) Visual and auditory evoked potentials can be recorded in the medial thalamus as well.     

Effects of thalamic parafascicular stimulation on the periaqueductal gray and adjacent reticular formation neurons. A possible contribution to pain control mechanisms

To investigate the mechanism of analgesic effect of electrical stimulation of the thalamic parafascicular nucleus (Pf), we studied modulations of neuronal activities in the periaqueductal gray (PAG) and the adjacent reticular formation (RF) in response to Pf electrical and peripheral noxious stimulations in the rat. Extracellular single unit activities were recorded from 129 neurons in the PAG and adjacent RF under light halothane anesthesia. Pf stimulation caused neuronal responses in approximately 80% of the PAG and adjacent RF neurons, and noxious stimulation in 75%, with predominant excitatory responses to either stimulation. When the responses to the two stimuli were tested in the same neurons (n = 69), 91% responding to noxious stimuli also responded to Pf stimuli, again with predominant excitatory responses to either stimulation. The PAG and adjacent RF neurons that were verified antidromically to project to the nucleus raphe magnus (NRM), showed a similar pattern of response (n = 20). These results suggest that a sizeable population of neurons in the PAG and adjacent RF receives excitatory effects from the Pf and noxious afferents, and that part of these neurons projects to the NRM, which inhibits the dorsal horn cells of the spinal cord (the descending pain suppression system). Thus, part of the mechanism of the analgesic effects of Pf stimulation is due to activation of the descending pain suppression system by exciting the PAG and adjacent RF neurons. A possible role of noxious afferents on the negative feedback to pain mediation through this descending system also has to be considered.     

Regulation of unit activity in nucleus reticularis thalami by the mesencephalic reticular formation and the frontal granular cortex.

Recruiting responses and related synchronous activities appear to be mediated by thalamic inhibition originating in nucleus reticularis thalami, a structure jointly regulated by an ascending projection from mesencephalic reticular formation and a descending influence from the frontal cortex. Extracellular unit activity was recorded in the anterior nucleus reticularis thalami (RVA) during recruiting responses, augmenting responses, stimulation of the mesencephalic reticular formation (MRF), and cryogenic blockade of the inferior thalamic peduncle (ITP). During recruiting responses, RVA units responded to medial thalamic (MT) stimulation with prolonged high frequency bursts. Analysis of the post-stimulus time histograms of these responses showed tham to have the same latency, duration, incrementing character, and envelope shape as the phasic thalamic inhibitory postsynaptic potentials (IPSPs) which appear to mediate recruiting responses. Brief stimulation of the MRF, which abolishes recruiting responses and thalamic IPSPs, prevented the response of RVA units to MT stimuli, and inhibited the spontaneous discharge of these units for 20 sec or more. We propose that the desynchronizing effect of MRF activation results from the abolition of thalamic inhibition originating in RVA. Cryogenic blockade of the ITP, which abolishes recruiting responses in the thalamus and cortex, also prevented R units from responding to MT stimuli. This result suggests that the MT activates R units via a thalamo-frontocortico-R pathway and explains the long latency of R bursts and thalamic IPSPs following MT stimulation. R cells that fired prolonged bursts during recruiting responses did not respond during augmenting responses. This result suggests that separate thalamic inhibitory mechanisms are involved in these two types of synchronization.     

Viscerosomatic convergence and responses to intestinal distension of neurons at the junction of midbrain and posterior thalamus in the cat

In cats anesthetized with sodium pentobarbital, microelectrode recordings were made from single neurons in the posterior thalamic region of termination of the spinothalamic tract (medial magnocellular division of the medial geniculate) and adjoining mesencephalic reticular formation, to determine if they receive input of visceral as well as of somatic origin. Of 309 units encountered, 136 (44%) demonstrated viscerosomatic convergency by responding to electrical stimulation of the greater splanchnic nerve as well as a somatic nerve (superficial radial and/or posterior tibial). Of 125 units tested, 42 (34%) had large somatic receptive fields spanning two or more limbs. Most of these responded best to intense skin stimuli (pressure, pinch, sometimes noxious heating). The remaining 83 had receptive fields restricted to part of one limb, and most of these responded to weak stimuli (e.g., hair movement, light tap) with no increment in responses to stronger stimuli. To determine of neurons in this region respond to intense visceral stimulation, the small intestine was distended by inflation of a balloon catheter which was inserted into a fistulated portion of the jejunum. Of 134 units with splanchnic nerve input, 28 responded to intestinal distension. Nine units responded only during the initial phase of distension. The other 19 units responded for all or part of the stimulus duration. Each of these 19 units tested had large somatic receptive fields, and most responded best to strong stimuli (e.g., pinch). In addition, they typically had thresholds for electrical stimulation of the splanchnic nerve which were well above threshold for the viscerointercostal reflex, suggesting that the input was mediated by Aδ-C fibers.     

Corticofugal influences on thalamic neurons during nociceptive transmission in awake rats

Pain is a multidimensional phenomenon and processed in a neural network. The supraspinal, brain mechanisms are increasingly recognized in playing a major role in the representation and modulation of pain. The aim of the current study is to investigate the functional interactions between cortex and thalamus during nociceptive processing, by observing the pain-related information flow and neuronal correlations within thalamo-cortical pathways. Pain-evoked, single-neuron activity was recorded in awake Sprague-Dawley rats with a Magnet system. Eight-wire microarrays were implanted into four different brain regions, i.e., the primary somatosensory (SI) and anterior cingulate cortex (ACC), as well as ventral posterior (VP) and medial dorsal thalamus (MD). Noxious radiant heat was delivered to the rat hind paws on the side contralateral to the recording regions. A large number of responsive neurons were recorded in the four brain areas. Directed coherence analysis revealed that the amount of information flow was significantly increased from SI cortex to VP thalamus following noxious stimuli, suggesting that SI cortex has descending influence on thalamic neurons during pain processing. Moreover, more correlated neuronal activities indicated by crosscorrelation histograms were found between cortical and thalamic neurons, with cortical neurons firing ahead of thalamic units. On basis of the above findings, we propose that nociceptive responses are modulated by corticothalamic feedback during nociceptive transmission, which may be tight in the lateral pathway, while loose in the medial pathway.     

The effect of morphine on responses of mediodorsal thalamic nuclei and nucleus submedius neurons to colorectal distension in the rat

In halothane-anesthetized rats, we characterized the responses of single neurons in the nuclei of medial thalamus (MT), specifically the mediodorsal thalamic nucleus (MD) and the nucleus submedius (Sm), to a noxious visceral stimulus (colorectal balloon distension, CRD), and studied the effects of intravenous morphine (Mor) on these responses using standard extracellular microelectrode recording techniques. 62 MD and 46 Sm neurons were isolated on the basis of spontaneous activity. 47 of the MD neurons (76%) responded to CRD, of which 70% had excitatory and 30% had inhibitory responses. 38 of the Sm neurons (83%) responded to CRD, of which 89% had excitatory and 11% had inhibitory responses. Responses of MD and Sm neurons excited by CRD were related significantly to distension pressure (20–100 mmHg), with maximum excitation occurring at 60 and 100 mmHg, respectively. MD neurons inhibited by CRD also had graded responses to graded CRD, with maximum inhibition occurring at 80 mmHg. The responses to noxious (pinch, heat) and nonnoxious (tap, brush) cutaneous stimuli were studied in 59 of the MD and 44 of the Sm neurons isolated. 22 of the MD neurons (37%) studied had cutaneous receptive fields, of which 59% were large and bilateral, 41% were small and usually contralateral receptive fields. 55% of these neurons were nociceptive-specific, 45% responded to both noxious and nonnoxious cutaneous stimulation. 29 of the Sm neurons (66%) studied had cutaneous receptive fields, of which 72% were large and usually bilateral, 14% were small and bilateral, 14% were small and contralateral receptive fields. 90% of these neurons were nociceptive-specific, 10% responded to both noxious and nonnoxious stimulation. No MD or Sm neurons responded exclusively to nonnoxious cutaneous stimulation. Mor (0.125, 0.25, 0.5 and 1 mg/kg IV) attenuated MD and Sm neuronal excitatory responses to CRD in a dose-dependent fashion, abolishing evoked activity with a dose of 0.5 mg/kg (p<0.05) and 1 mg/kg (p<0.05), respectively. Naloxone (0.4 mg/kg IV) reversed the effects of Mor. Mor and naloxone had no effects on spontaneous activity. These data support the involvement of MD and Sm neurons in visceral nociception, and are consistent with a role of Sm in affective-motivational, and MD in both sensory-discriminative and affective-motivational aspects of nociception.     

Inhibition of spontaneous and evoked unit activity in the rat medial prefrontal cortex by mesencephalic raphe nuclei

The rat medial prefrontal cortex (PFC) receives a serotoninergic (5-HT) innervation which originates from the mesencephalic raphe nuclei. In the present study we determined the influence of the 5-HT ascending systems on the spontaneous and evoked activity of PFC neurons in anesthetized rats. Stimulation of the dorsal (DRN) and of the median raphe (MRN) nuclei inhibited the spontaneous activity of 35.0% and 52.8% of the PFC cells tested (mean duration of the inhibition: 75.5 and 82.2 ms, respectively). These inhibitory responses are likely mediated by the 5-HT-containing neurons since they were decreased markedly following selective destruction of ascending 5-HT pathways induced by local injections of 5,7-dihydroxytryptamine. Moreover, the inhibitory effect of MRN stimulation could be blocked by systemic administration of the 5-HT2 receptor antagonists: ketanserin and ritanserin. The effects of MRN stimulation on two types of evoked responses were studied. The excitatory responses of PFC neurons induced by the stimulation of the mediodorsal nucleus of the thalamus (MD) were inhibited by MRN stimulation applied before that of MD. Similarly, the activation of PFC cells induced by a noxious tail pinch was suppressed by a concomitant stimulation of the MRN. These results indicate that 5-HT neurons exert an inhibitory control on spontaneous or evoked activity in the rat PFC.     

Serotonin Mediates Suppression of Focal Epileptiform Activity Induced by Noxious Stimulation

Noxious stimulation can suppress epileptic seizures in humans and epileptiform activity in laboratory animals. Using as a model system the focal epileptiform activity (FEA) induced by the pneumophoresis of penicillin, the role of 5-hydroxytryptamine (5HT) in suppression of this activity by noxious stimulation was investigated. Drugs known to depress dorsal raphe unit activity, (+/-)-8-hydroxydipropylaminotetralin (DPAT), imipramine, and fluoxetine prevented suppression of FEA induced by noxious stimulation. Desimipramine, which depresses locus ceruleus but not dorsal raphe unit activity, was ineffective in blocking the suppression. Quipazine, an agonist at 5-HT receptors, in part restored the suppression that had been blocked by DPAT or imipramine. Several serotonin antagonists effective at 5-HT1 and 5-HT2 receptors blocked suppression, but an unequivocal determination of the serotonin receptor subtype mediating suppression could not be made. We conclude that 5-HT mediates suppression of FEA induced by noxious stimulation.     

Serotonin involvement in descending inhibition of spinal nociceptive transmission produced by stimulation of medial diencephalon and basal forebrain

The responses of single lumbar dorsal horn neurons to noxious radiant heat stimuli (50 degrees C, 10 sec) applied to glabrous footpad skin were recorded in cats anesthetized with sodium pentobarbital and 70% N2O. Responses were markedly reduced during electrical stimulation (100-msec trains at 100 Hz, 3/sec, up to 400 microA) at sites in the medial diencephalic periventricular gray (PVG), preoptic area, and basal forebrain. A role for serotonin (5-hydroxytryptamine, 5-HT) was investigated by determining whether descending inhibition from these areas could be affected by (1) acute systemic administration of the 5-HT antagonist methysergide, or (2) depletion of central 5-HT levels by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA; 500 mg/kg, i.p.). Inhibition produced by stimulation at these sites was reduced or abolished in 22 cases following administration of methysergide (0.2 to 1 mg/kg) to non-pretreated cats. In the PCPA-pretreated cats, stimulation in preoptic or basal forebrain areas inhibited the responses of 26 units to noxious skin heating to varying degrees; PVG stimulation inhibited the responses of 14 of 26 units, while the remainder were unaffected. The mean current threshold for inhibition produced by PVG or preoptic/basal forebrain stimulation was significantly higher, while mean inhibition at 200 microA was significantly lower, in units from PCPA-pretreated cats compared to those from non-pretreated cats. The results indicate that 5-HT may be involved in the mediation of spinal inhibition produced by medial diencephalic and basal forebrain stimulation.     

The effects of electrical stimulation of nucleus raphe magnus and nucleus reticularis gigantocellularis on medial thalamic neurons--special reference to noxious neurons

Many previous studies revealed that electrical stimulation of brainstem inhibits activities of spinal dorsal horn cells, and that the inhibitory fibers, especially raphe-spinal system, descend in the dorsolateral funiculus (DLF) of the spinal cord. But the effect of such stimulation upon thalamic neurons are still unknown. The author tried to reveal how the stimulation of the nucleus raphe magnus (NRM) and the nucleus reticularis gigantocellularis (NGC) affect the medial thalamic neurons. Thirty-two adult cats (2.0-5.0 kg) were anesthetized with pentobarbital and immobilized by succinil choline infusion, and were maintained with 0.3-0.5% of halothane during experiments. The sural nerve was exposed and electrically stimulated with an intensity strong enough to activate C-fibers. To record single unit responses from the medial thalamus, a tungsten microelectrode (1.2-5 M omega at 1000 Hz) was inserted through a burr hole near the vertex contralateral to the sural nerve stimulation. Posterior fossa craniectomy was performed to insert 3 stimulation electrodes into NRM and bilateral sides NGC. Total of 183 single units were recorded from the medial thalamic region. They were classified into 45 noxious (N), 29 tap (T), 105 spontaneous (S) and 4 inhibitory (I) types according to the response patterns to contralateral sural nerve stimulation. N type neurons were mainly in the parafascicular region (Pf) and subparafascicular region (Spf). NRM stimulation (333Hz, 100-200 microA) inhibited 84% of N type, 57% of T type and 46% of S type neurons. The inhibitory ratio of N type neurons is significantly (p less than 0.01) higher than those of T and S type neurons, but there is no significant difference between T and S type.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cortical representation of pain in primary sensory‐motor areas (S1/M1)—a study using intracortical recordings in humans

Intracortical evoked potentials to nonnoxious Aβ (electrical) and noxious Aδ (laser) stimuli within the human primary somatosensory (S1) and motor (M1) areas were recorded from 71 electrode sites in 9 epileptic patients. All cortical sites responding to specific noxious inputs also responded to nonnoxious stimuli, while the reverse was not always true. Evoked responses in S1 area 3b were systematic for nonnoxious inputs, but seen in only half of cases after nociceptive stimulation. Nociceptive responses were systematically recorded when electrode tracks reached the crown of the postcentral gyrus, consistent with an origin in somatosensory areas 1–2. Sites in the precentral cortex also exhibited noxious and nonnoxious responses with phase reversals indicating a local origin in area 4 (M1). We conclude that a representation of thermal nociceptive information does exist in human S1, although to a much lesser extent than the nonnociceptive one. Notably, area 3b, which responds massively to nonnoxious Aβ activation was less involved in the processing of noxious heat. S1 and M1 responses to noxious heat occurred at latencies comparable to those observed in the supra‐sylvian opercular region of the same patients, suggesting a parallel, rather than hierarchical, processing of noxious inputs in S1, M1 and opercular cortex. This study provides the first direct evidence for a spinothalamic related input to the motor cortex in humans. Hum Brain Mapp 34:2655–2668, 2013. © 2012 Wiley Periodicals, Inc.     

Noxious and non-noxious responses in the medial thalamus of the rat

Single-cell experiments were undertaken to localize and characterize the medial thalamic (MT) neurons which respond to noxious and non-noxious input in the rat. The observations demonstrated that: (1) 61 and 42% of MT neurons respond to noxious (Nox) and non-noxious (NN) stimulation, respectively; (2) MT neurons exhibit 4 cell types according to their pattern of response; Type A units were excited exclusively by Nox stimulation; Type B units were excited exclusively by NN stimulation; Type C units were excited by both (Nox and NN) stimulation, and Type D units exhibited decreases in firing rate following both stimulation modalities; (3) neurons of the parafascicularis nucleus exhibit more noxious responses (Type A units) than other medial thalamic areas.     

Neuronal responses to 5-hydroxytryptamine and dorsal raphe stimulation within the globus pallidus of the rat

The projection from the dorsal raphe nucleus (DRN) to the globus pallidus (GP) was investigated electrophysiologically, in the urethane-anesthetized rat together with the responsiveness of cells in the GP to 5-hydroxytryptamine (5-HT) and noradrenaline (NA). The majority of spontaneously active cells in the GP had high regular firing rates. They were unaffected by both DRN stimulation (69/83 cells) and iontophoretically applied 5-HT (38/63 units) or NA (30/42 units) but were inhibited by GABA. A few cells (N = 10) were recorded from, that were spontaneously active but with a much lower and less regular firing rate, which, however, seemed to be much more responsive to 5-HT. In addition, DL-homocysteic acid (DLH) was used to activate silent cells and all seven cells activated in this manner were inhibited by 5-HT. In addition 5/6 cells that had their firings maintained by DLH were inhibited by stimulation of the dorsal raphe. The results show a lack of responsiveness to both 5-HT and DRN stimulation of the typically regular spontaneously active pallidal neurons. There seems to be a small population of normally quiescent cells, however, that is sensitive to 5-HT and receives an input from the DRN.