Response properties of nociceptive and low-threshold mechanoreceptive neurons in the hamster superior colliculus

There are many somatosensory neurons in the hamster superior colliculus (SC); some respond to innocuous tactile stimuli, while others respond either preferentially, or solely, to noxious stimuli. Yet, there are little quantitative data describing the responses of these neurons. We sought to provide such information by relating stimulus intensity to the magnitude of the neural response using controlled innocuous and noxious mechanical and thermal stimuli. Of 122 somatosensory SC neurons studied in urethane-anesthetized hamsters, the majority (52%) had low-threshold mechanoreceptive properties (LT). LT neurons had force thresholds less than 1 gm, adapted rapidly to maintained stimuli, and did not respond with higher numbers of impulses to noxious mechanical or thermal stimuli. A smaller, though substantial, proportion of neurons (45%) responded either preferentially, or solely, to noxious stimuli. A few neurons (3%) were inhibited by either light tactile or noxious mechanical stimuli. Two populations of nociceptive neurons were found and classified either as wide dynamic range (WDR) neurons (n = 25), those that responded to gentle mechanical, noxious mechanical, and/or thermal stimuli; or nociceptive-specific (NS) neurons (n = 30), those that responded solely to high-intensity mechanical or noxious thermal stimuli. WDR neurons responded monotonically to increases in the intensity of innocuous mechanical stimuli, and displacement-response relationship for this population was a slightly negatively accelerating power function with an exponent of 0.785. However, the thermal stimulus-response relationships (to graded skin temperatures) of both WDR and NS neurons were positively accelerating power functions with exponents of 2.3 and 2.5 (r2 = 0.988), respectively. These values are consistent with both electrophysiological data from dorsal horn nociceptive neurons and from human psychophysical results using the same range of thermal stimuli. These experiments demonstrate that SC neurons are capable of signaling not only the presence and location of a noxious stimulus but its intensity as well. Presumably, these neurons play a significant role in the animal's reactions to potentially harmful stimuli. The partial laminar segregation of WDR and NS neurons may reflect different involvements of particular nociceptive subtypes in the various overt responses mediated by the SC.     

Psychophysics of CNS pain-related activity: binary and analog channels and memory encoding.

The forebrain neuronal system signaling pain has been poorly characterized. The pain pathway afferent to the thalamus may be a labeled line consisting of neurons in the pain-signaling pathway to the brain (spinothalamic tract, STT) that respond only to painful stimuli. It has recently been proposed that the STT contains a series of analog-labeled lines, each signaling a different aspect of the internal state of the body (interoception), for example, visceral/cold/itch sensations. In this view, pain is the unpleasant emotion produced by disequilibrium of the internal state. The authors now show that stimulation of an STT receiving zone (thalamic principal somatic sensory nucleus, ventral caudal) in awake humans produces two different exteroceptive responses. The first is a binary response signaling the presence of painful stimuli. The second is an analog response in which nonpainful and painful sensations are graded with intensity of the stimulus. Such stimulation can evoke both the sensory and emotional components of previously experienced pain. These results illustrate the diverse functions of human pain signaling pathways.     

Vestibular, somatosensory, and auditory input to the thalamus of the cat.

Responses were recorded and analyzed for 334 single units in the ventral, posterior, and intralaminar groups of thalamic nuclei of the cat. Units were tested for a response after (i) electrical stimulation of the vestibular nerve: (ii) electrical stimulation of the four paw pads and natural stimulation of joint, muscle, and cutaneous receptors of the limbs, trunk, and head (somatic stimulation); and (iii) electrical stimulation of the cochlear nerve and sound (auditory stimuli). Forty-one percent of the units responded to these stimuli. Vestibular stimulation activated 16% of the responsive units. These units were found primarily in the posterior nucleus and the border region between it and the ventral posterolateral nucleus. Seventy-three percent of vestibular-activated units also responded to at least one other modality of sensory stimuli. No evidence was found for a thalamic region where the majority of units responded at short latency to vestibular nerve stimulation. Ninety percent of the responsive units were activated by somatic stimuli. These units could be divided into two groups. One group was composed of units that were activated exclusively by somatic stimuli and had a small contralateral receptive field. These units were found primarily in the ventral posterolateral nucleus. The other group had a bilateral receptive field or was activated by more than one modality of sensory stimuli. These units were found primarily in the posterior nucleus and the border area of the ventral posterolateral nucleus. Units that responded to auditory stimulation (10% of responsive units) were found in the posterior nucleus and the medial geniculate nucleus.     

Chronic Spinal Nerve Ligation Induces Changes in Response Characteristics of Nociceptive Spinal Dorsal Horn Neurons and in Their Descending Regulation Originating in the Periaqueductal Gray in the Rat

We studied whether a chronic neuropathy induced by unilateral spinal nerve ligation changes the response characteristics of spinal dorsal horn wide-dynamic range (WDR) neurons or their periaqueductal gray (PAG)-induced descending modulation. Experiments were performed in rats with behaviorally demonstrated allodynia induced by spinal nerve ligation and in a group of nonneuropathic control rats. The stimulus–response functions of WDR neurons for mechanical and thermal stimuli and the modulation of their peripherally evoked responses by electrical stimulation of the PAG were determined under pentobarbital anesthesia. The results showed that neuropathy caused a significant leftward shift in stimulus–response functions for mechanical stimuli. In contrast, stimulus–response functions for noxious heat stimuli in the neuropathic limb were, if anything, shifted rightward, although this shift was short of statistical significance. In neuropathic rats, PAG stimulation produced a significantly stronger attenuation of spinal neuronal responses induced by noxious heat in the unoperated than in the operated side. At the intensity that produced attenuation of noxious heat stimuli, PAG stimulation did not produce any significant change in spinal neuronal responses evoked by mechanical stimuli either from the operated or the nonoperated hindlimb of the neuropathic rats. Spontaneous activity of WDR neurons was higher in the operated side of neuropathic rats than in control rats. Afterdischarges evoked by peripheral stimuli were observed in 1/16 of the WDR neurons ipsilateral to spinal nerve ligation and not at all in other experimental groups. The WDR neurons studied were not activated by innocuous or noxious cold stimuli. The results indicate that spinal nerve ligation induces increased spontaneous activity and enhanced responses to mechanical stimuli in the spinal dorsal horn WDR neurons, whereas noxious heat-evoked responses are not significantly changed or if anything, attenuated. Moreover, the inhibition of noxious heat stimuli by PAG stimulation is attenuated in the neuropathic side. It is proposed that the observed changes in the response characteristics of the spinal dorsal horn WDR neurons and in their descending modulation may contribute to the neuropathic symptoms in these animals.     

Anatomical distribution and sensory properties of brain stem and posterior diencephalic neurons responding to genital, somatosensory, and nociceptive stimulation in the squirrel monkey.

In chloralose-urethane-anesthetized female squirrel monkeys, 325 single units sampled from a region extending from the caudal medulla to the posterior diencephalon were examined for responsiveness to genital, rectal, innocuous somatosensory, and various forms of nociceptive stimulation. The units were highly responsive, with 84% responding to at least one stimulus type. The responsive units were widely distributed in the brain stem tegmentum, deep tectum, and posterior diencephalon. Very few neurons responded to only one type of stimulation. The patterns of convergent responsiveness to the various stimulus types were not, however, a simple random function of unit responsiveness to each type of stimulus per se. Unit responses to vaginal stimulation consisted of simple increases or decreases in firing which outlasted the duration of the probing stimulus in most cases. Some units responded more strongly to cervical than to vaginal tract stimuli. The somatic receptive fields of units responding to touch-pressure stimuli were typically bilateral and quite extensive. A forceps pinch of nociceptive intensity elicited a response from 64% of the cells, and of these, 11% showed significant linear correlations between their firing rates and increasing pinch pressure in the nociceptive intensity range. Brief, localized nociceptive thermal stimuli and needle pricks failed to elicit responses from the neurons tested. Based on a comparison between the response properties of monkey brain stem neurons and the previous findings for rat and cat neurons, it was concluded that brain stem cells display species-typical sensory characteristics which have parallels in the properties of behavioral responses of these three species to genital and other sensory stimuli. Properties of unit responses to nociceptive stimuli have implications in relation to the neural mechanisms of first and second pain.     

Response characteristics of lamb trigeminal neurons to stimulation of the oral cavity and epiglottis with different sensory modalities

A region of the trigeminal complex located at the border of the subnucleus interpolaris and subnucleus caudalis receives not only trigeminal nerve inputs from the face, tongue and palate, but also afferent terminations from other nerves which innervate the oral cavity and upper airway. To increase our understanding of the types of sensory information relayed to this region of the trigeminal nucleus, we investigated the response characteristics of single neurons to stimulation of the tongue, palate and epiglottis. Receptive field size and location of 83 trigeminal neurons were mapped, and responses to mechanical, thermal and chemical stimuli were recorded. About 90% of the neurons had one receptive field and no convergence between the oral cavity and epiglottis was observed. Furthermore, only about 15% of the trigeminal neurons responded to more than one stimulus modality. A moving mechanical stimulus elicited responses in over 90% of the cells, and 84% responded to moving and punctate mechanical stimuli. These mechanosensitive neurons generally exhibited rapidly adapting responses. Thermal and chemical stimuli were relatively ineffective. Cooling a receptor surface most often produced excitation, and warming inhibition. Responses to chemical stimuli were only observed for salts at high concentrations. These results suggest that, like oral cavity information relayed by the trigeminal nerve, afferent terminations in the trigeminal nucleus from other nerves subserving the oral cavity and upper airway function to relay mechanical sensory information.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spinal cord injury triggers sensitization of wide dynamic range dorsal horn neurons in segments rostral to the injury

A spinal cord injury (SCI) was produced in adult rats by complete spinal cord transection at L6-S1. Neuropathic pain behaviors similar to the chronic central pain (CCP) syndrome in human, such as thermal hyperalgesia, mechanical allodynia and autotomy, were present in these rats after spinal cord injury. Meanwhile, wide dynamic range (WDR) neurons recorded in the spinal dorsal horn rostral to the lesion responded as high frequency of spontaneous activities, long duration of after-discharges to noxious electrical stimuli and an augmented wind-up to 0.5 Hz stimuli. By using bupivacaine powder, a sodium channel blocker, at the locus of transection immediate after nerve injury, the chronic pain behaviors were prevented; the hyperexcitability of WDR neurons was also substantially reduced. It is suggested that spinal cord transection induces the CCP syndromes, which may be evoked and maintained by the hyperexcitability in WDR neurons rostrally. Reducing the neuronal activity at the site of lesion following injury may prevent the development of CCP after SCI.     

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.     

Short-latency responses of neurons of the striate system of the brain to sensory activation

Experiments were carried out on awake cats to study responses of caudate neurons to different afferent stimuli (visual, auditory, somatic and direct electrical stimulation of medial geniculate body). Mean response latencies varied within 15-55 ms with the maximum value to 200 ms. At the same time 1-10% of cells responded with short latency to all applied stimuli. Significance of short-latency sensory responses in comprehension of principles of sensory processing in non-specific subcortical structures is discussed.     

Neonatal ventral hippocampal lesions modify pain perception and evoked potentials in rats

This work concerns the debate surrounding the modified pain reactivity of patients with schizophrenia and other possible perceptive distortions. Rats with a neonatal ventral hippocampal lesion (NVHL) were used to model the neuro-developmental aspect of schizophrenia, and their reactivity to various stimuli was evaluated. The results could also help understand sensory deficits in other neuro-developmental disorders. Behavioural reactions to graduated painful thermal and mechanical stimuli were observed, and evoked potential responsiveness to tactile, visual and acoustic non-painful stimuli was recorded and compared to non-operated and sham lesioned controls. A higher threshold was observed with painful mechanical stimuli and shorter paw withdrawal latency with thermal stimuli. This was particularly relevant as there was no change in the evoked potentials triggered by non-nociceptive tactile stimulation of the same part of the body. There was a 10dB(A) increase in the auditory threshold and a suppression of auditory sensory motor gating. Visually evoked potentials did not appear to be affected. Taken together, the results showed that NVHL-evoked alteration of brain development induces mechanical hypoalgesia, thermal hyperalgesia and auditory sensory changes. The data also contribute towards elucidating mechanisms underlying sensory deficits in neurodevelopmental diseases, including schizophrenia.     

Sensory functions in chronic neuralgia.

Eleven patients with sustained neuralgia, in most cases after traumatic nerve lesion, were subjected to quantitative sensory testing with thermal and non-noxious mechanical stimuli. Measurements were made in the pain area and at a homologous site on the contralateral normal side. All patients were hypoaesthetic with raised thresholds for warm and cold or touch, or both. Thermal pain thresholds were also raised in some patients but lowered in others indicating hypersensitivity of the nociceptor system or dysaesthesia for thermal input. In six patients single mechanical stimuli produced a painful response above the touch detection threshold. Reaction time measurements indicated that this painful response to suprathreshold mechanical pulses was measured by magnitude estimation as a function of stimulus amplitude. The results were fitted by power functions, as in normal skin, but with steeper slopes on the abnormal side. Suprathreshold hyperaesthesia (recruitment) may exist in the presence of normal threshold functioning.     

Responses of cat C1 spinal cord dorsal and ventral horn neurons to noxious and non-noxious stimulation of the head and face

Previous anatomical studies have shown that trigeminal and cervical afferent nerve fibers project to the upper cervical segments of the spinal cord. To determine the response properties of neurons in the upper cervical spinal cord, we studied the response of C1 dorsal and ventral horn cells to electrical and graded mechanical stimulation of the face, head and neck in anesthetized cats. Neurons were classified as low-threshold-mechanoreceptive (LTM), wide-dynamic-range (WDR), nociceptive-specific (NS) or unresponsive, based on their responsiveness to graded mechanical stimulation. Extracellular single unit recordings were obtained from 118 neurons excited by cervical (24), trigeminal (39) or both cervical and trigeminal (55) stimulation and from 24 neurons unresponsive to peripheral stimulation. Based on neuronal mechanical response properties, 52.2% of the responsive neurons were classified as LTM, 35.9% as WDR and 11.9% as NS. WDR neurons exhibited more convergence and had larger receptive fields than either NS or LTM neurons. WDR and NS neurons had longer first spike latencies than LTM neurons at all tested sites. Only WDR neurons were found to project to the contralateral caudal thalamus. Within C1, LTM neurons were located primarily in laminae III and IV, WDR neurons in lamina V and NS neurons in laminae VII and VIII. These data suggest that some neurons in the first cervical segment of the spinal cord receive convergent input from trigeminal and cervical pathways and may be involved in mediating orofacial and cranial pain.     

Midbrain and pontine unit responses to lordosis-controlling forms of somatosensory stimuli in the female golden hamster

In the sexually receptive female hamster, stimulation of the flanks, perineum, rump, back, or thorax can elicit lordosis. Stimulation of the face or forepaws is disruptive of ongoing lordosis. Single units in the midbrain and pons of sexually receptive female hamsters were tested for responsiveness to these lordosis-controlling stimuli. The animals were either anesthetized with urethane or unanesthetized and paralyzed at the time of recording. The brain stem cells were quite responsive under both conditions, with 81% of 180 neurons responding to somatic stimulation. In the anesthetized animals, somewhat fewer cells responded to somatosensory stimuli, and lordosis-eliciting types of stimuli were more effective than face or forepaw stimulation. In the dorsal midbrain, responsive units lay in the deep tectum, intercollicular region, and a zone lateral to and extending into the central gray. In the ventral midbrain and pontine tegmentum, the responsive cells were not clustered in any particular loci. Some cells in the deep tectum and adjacent regions of the dorsal midbrain displayed opposing changes in firing in response to lordosis-promoting and lordosis-disrupting types of stimuli. Units responding to flank stimulation usually responded to stimulation of either flank alone, but often showed a more pronounced response to bilateral than to unilateral stimulation. It was concluded that the somatosensory properties and anatomical distribution of many of the brain stem neurons were compatible with a role in the control of the lordosis response in the hamster.     

Paraventricular hypothalamic oxytocinergic cells responding to noxious stimulation and projecting to the spinal dorsal horn represent a homeostatic analgesic mechanism

The participation of the hypothalamic paraventricular nucleus (PVN) in an endogenous central mechanism of analgesia has been observed using rats in various experimental procedures including electrophysiological and behavioral tests. However, little is known about the PVN neuronal responses to noxious stimulation. The only data available indicate a c-fos increase after noxious visceral stimulations. Our electrophysiological recordings of single PVN cells showed that, out of 223 cells, 79 responded to noxious mechanical and/or thermal stimuli, and another 10 responsive cells were found in the Reuniers thalamic nucleus. These cells responded only to noxious stimuli mainly in the ipsilateral hind limb but we also observed cells responding to stimulation of both hind limbs and also the tail. Mechanical stimulation was most effective but some cells could respond to both mechanical and thermal noxious stimuli. Some of the responding PVN cells were identified by antidromic stimulation in the ipsilateral lumbar dorsal horn spinal cord. Finally, in order to document the nature of the neurotransmitter and the projection to the spinal cord of the PVN cells that responded to noxious stimulation, we used a juxtacellular approach to record and stain some neurons and found them to be oxytocinergic by immunofluorescence procedures. The PVN cells activated by noxious stimuli may suppress the peripheral incoming afferent A-delta and C fibers, completing a circuit involved in diffuse endogenous analgesia. This mechanism strongly suggests that the PVN participates in a homeostatic mechanism involved in pain and analgesia.     

Suppression of neurokinin-1 receptor in trigeminal ganglia attenuates central sensitization following inflammation

This study examined whether local application of a neurokinin-1 (NK1) receptor antagonist into the trigeminal ganglia (TRGs) modulates hyperexcitability of trigeminal spinal nucleus caudalis (SpVc) wide-dynamic range (WDR) neuron activity innervating both the temporomandibular joint (TMJ) region and facial skin following TMJ inflammation. Extracellular single unit recording combined with multibarrel electrodes was used. TMJ inflammation was induced by the injection of complete Freund's adjuvant (CFA). WDR neurons responding to electrical stimuli of the TMJ region and facial skin were recorded from the SpVc in anesthetized rats. The spontaneous and mechanical stimulation-induced discharge frequencies of WDR neurons were significantly larger in inflamed rats than in control rats. The spontaneous WDR activities were current-dependently decreased by local iontophoretic application of an NK1 receptor antagonist into the TRGs after 1 and 2 days of inflammation. The firing frequency of WDR neurons and threshold evoked by mechanical stimulation of facial skin returned to control levels by application of the NK1 receptor antagonist into TRGs after 1 day, but not 2 days, of inflammation. These results suggest that in the early stages of inflammation suppression of the NK1 receptor mechanism in TRGs may prevent central sensitization of SpVc nociceptive neurons.     

Selectivity in the reinnervation of iris and adrenal medulla by superior cervical ganglion after transplantation under the kidney capsule

A previous gross evoked potential study revealed that although multisensory convergence characterizes the entire claustrum, it is a complex, regionally differentiated formation that receives sensory afferents via primary and non-specific pathways. In the present study the responses of individual claustral neurons to somatic stimulation, clicks and flashes were investigated in immobilized cats with and without chloralose anesthesia.Of 397 neurons, 31% were unresponsive to any of the sensory stimuli that were used. The 275 responsive neurons formed a heterogeneous population and were distributed throughout the structure with no apparent order. Ninety percent were activated by somatic stimulation, 48% by click and 5% by flash. Among somatic cells 18% had ‘restricted’ or ‘highly restricted’ fields, 38% had widespread fields and 44% responded to more than one sensory modality. All somatic cell types were driven by mechanical stimulation of the skin or of deep tissues, and no correlation as found between the cell type and a given stimulus type. Latency distribution studies of somatic cells confirmed the macrophysiological subdivision of the structure into anterior, intermediate and posterior regions.Among auditory neurons, 17% responded only to a click and 83% were multisensory. In contrast to the somatic response, click-evoked response properties were determined by the cell type irrespective of the recording site. Though flash was not tested for in all convergent units, only two units were encountered which were activated by flash alone. In total, 75% of the responsive cells showed heterotopic or heterosensory convergence properties, while 25% were specific. Interaction between pairs of different stimuli varied from neuron to neuron and complex interaction patterns were observed. These data confirm the functional non-homogeneity of the claustrum and indicate that sensory afferents from various origins are distributed differently inside the structure and terminate in different combinations upon individual neurons.Comparison of animals with and without chloralose showed that the neuronal populations were similar in regard to overall responsiveness and the respective proportions of convergent and specific neurons. Response types, however, were markedly different in the two preparations. Under chloralose excitatory responses were rather stereotypical and inhibitory effects were difficult to assess due to the silence of the majority of cells. Without chloralose, excitatory responses were long and complex and inhibitory responses (either initially or following excitation) were predominant. In both preparations, spontaneous firing rates were low and rhythmic responses, as well as the driving up of unresponsive neurons by repetitive stimulation, were observed.The data presented are discussed with regard to the functional significance of the claustrum in sensory perception and in regulating non-sensory functions.     

Properties of nociceptive and non-nociceptive neurons in trigeminal subnucleus oralis of the rat

Recent studies have provided evidence suggesting the involvement of rostral components of the V brainstem complex such as trigeminal (V) subnucleus oralis in orofacial pain mechanisms. Since there has been no detailed investigation of the possible existence of nociceptive oralis neurons in the rat to substantiate this recent evidence, the present study was initiated to determine if neurons responsive to noxious orofacial stimuli were present in subnucleus oralis and to characterize their functional properties. In anesthetized rats, recordings were made of the extracellular activity of single neurons functionally characterized as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR) or nociceptive-specific (NS) neurons. The 342 LTM neurons responded only to light mechanical stimulation of orofacial tissues. The mechanoreceptive field of the LTM neurons included the intraoral region in 28% and was localized to the adjacent perioral area in 65%. For 95% the field was localized within one V division. Responses evoked in LTM neurons by electrical stimulation of the orofacial mechanoreceptive field revealed A fiber afferent inputs but no activity that could be attributed to C fiber afferent inputs. The 72 nociceptive neurons included 52 WDR neurons which responded to light (e.g. tactile) as well as noxious (e.g. heavy pressure; pinch) mechanical stimulation of perioral cutaneous and intraoral structures, and 20 NS neurons which responded exclusively to noxious mechanical stimuli. They also differed from the LTM neurons in that 36% of the WDR and 20% of the NS neurons had a mechanoreceptive field involving more than one V division. However, in accordance with our findings for the LTM neurons, the majority of WDR and NS neurons had a mechanoreceptive field involving the intraoral and perioral representations of the mandibular and/or maxillary divisions; those neurons having a mandibular field which especially included intraoral structures predominated in the dorsomedial zone of subnucleus oralis whereas those with a perioral mechanoreceptive field which particularly involved the maxillary division were concentrated in the ventrolateral zone of oralis. In contrast to the LTM neurons, 57% of the WDR and 67% of the NS neurons showed evidence of electrically evoked C fiber as well as A fiber afferent inputs from their mechanoreceptive field. We also noted suppression of the electrically evoked responses by heating of the tail or pinching of the paw. This effect was considered to be a reflection of diffuse noxious inhibitory controls, and was seen in NS as well as WDR neurons; most, but not all, of these neurons received A fiber as well as C fiber orofacial afferent inputs.(ABSTRACT TRUNCATED AT 400 WORDS)     

Representation of somatosensory modalities in pathways ascending from the spinal anterolateral funiculus to the thalamus demonstrated by lesions in man

Patients with cordotomies (16), and brainstem (17) or thalamic (30) infarcts, all except cordotomies verified by magnetic resonance imaging (MRI), have been subjected to quantitative sensory perception threshold testing (QST) for touch (von Frey), mechanical pain, sharpness, innocuous warmth and cold, and heat pain in the maximally affected body area and its unaffected contralateral mirror image region. Some patients were tested twice at widely spaced time intervals; no qualitative differences were found. Results show that all modalities are dissociable from one another by lesions at all levels tested, so that there must be separable representation for each of the six modalities tested. In the lower (crossed symptoms and signs), but not the upper (uncrossed symptoms), deficits for all modalities (except for touch) were more marked than at higher levels. At the level of the thalamus, deficits for innocuous and noxious thermal modalities but not for mechanical pain were recorded in the case of lesions of the principal somatosensory relay nucleus (VPL/Vc), while more medial thalamic lesions resulted in deficits for mechanical pain but not for heat pain or innocuous thermal modalities; there is a marked deficit for sharpness caused by lesions at both thalamic sites.     

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.     

Responses of neurons in nucleus ventralis posterolateralis of the cat thalamus' to hypogastric inputs

Recordings were made from 68 units in the nucleus ventralis posterolateralis (VPL) of the cat thalamus, which responded to stimulation of hypogastric afferents. These units also received nociceptive inputs from the contralateral integument. Units which responded exclusively to hypogastric afferent inputs were not found. Thirty seven of the units were nociceptive specific (NS), and the remaining 31 were wide dynamic range (WDR) units. All of these units were located in the shell region of the lateral subdivision of the caudal VPL. NS units responding to hypogastric afferent inputs had a circumscribed cutaneous receptive field on the contralateral abdomen, gluteal region, tail or hind limb. These areas corresponded to tactile dermatomes T13-S2. Similarly, the cutaneous receptive fields of WDR units receiving hypogastric afferent inputs were distributed in the contralateral abdomen, gluteal region, tail and hind limb, with the sole exception of one unit, whose receptive field also included a part of the lower thorax. These findings extend the previous findings that the shell region of the caudal VPL of the cat thalamus constitutes a thalamic link in a visceral pain pathway, and that the visceral and cutaneous pathways share a common projection locus in the VPL.