Responses of spinocervical tract neurones to noxious stimulation of the skin.

1. Activity of single spinocervical tract neurones has been recorded in the lumbar spinal cord of chloralose anaesthetized or decerebrated cats. Reversible spinalization was produced by cold block at L3. Sensitivity of these neurones to noxious stimulation was studied by heating their cutaneous receptive fields above 40-45 degrees C. 2. Most of the units were located in lamina IV of the dorsal horn and had their receptive fields in the ipsilateral foot. All but one of the studied neurones were excited by moving hairs or by gentle mechanical stimulation of the skin. 3. Eighty-four % of the units were affected by noxious stimuli and three kinds of response were obtained: (i) 61% were excited (E-cells) by noxious heat; (ii) 19% were inhibited (I-cells); and (iii) 19% gave a mixed response reversing from excitatory to inhibitory (EI-cells). 4. E-cells had axons with a wider range of conduction velocities than the rest and also received the strongest descending inhibition from supraspinal structures. 5. The recording sites of EI-cells were located in the medial third of the dorsal horn whereas E- and I-cells were distributed over the full width of the dorsal horn. 6. The possible role of the spinocervical tract in nociception is discussed.     

Functional organization of the sympathetic innervation supplying the hairless skin of the hindpaws in chronic spinal cats

1. Reflex activation of the sudomotor system supplying the cat's hindpaws to natural stimulation of skin has been investigated in chronic low thoracic spinal cats. The neuronal activation of the sweat glands was measured by recording the skin potentials from the surface of the hairless skin.
2. The sudomotor system was activated by mechanical and thermal noxious stimulation of skin and by stimuli which excited the Pacinian corpuscles in the paws. The reflexes were maximal some 50 to 75 days following spinalization.
3. Noxious stimulation of the skin was followed by an increase of the size and of the frequency of the resting activity in the sudomotor system. This increase of the resting activity lasted for 10 min or longer and was, in many preparations, especially pronounced 40 days or later after spinalization.
4. Neurophysiological investigations of postganglionic neurones in the medial plantar nerve in 10 chronic spinal cats (74 to 129 days after spinalization) revealed two populations of postganglionic neurones:type 1 neurones were excited by noxious cutaneous stimuli and by vibrational stimuli and classified as sudomotor neurones.Type 2 neurones were inhibited by noxious cutaneous stimuli applied to the ipsilateral hindfoot and mostly excited by noxious stimuli applied to the contralateral hindfoot and not affected by vibrational stimuli. These neurones were classified most likely as vasoconstrictor neurones.
5. The results argue that the chronic spinal cord contains reflex circuits relaying specific somatosympathetic reflexes to the sweat glands. Whether these spinal circuits are normally used in cats with intact CNS is an open question.

     

Physiological properties of sensory trigeminal neurons projecting to mesencephalic parabrachial area in the cat

1. One hundred forty-one trigeminomesencephalic neurons in the sensory trigeminal nucleus of cats anesthetized with alpha-chloralose were identified by antidromic stimulation of the mesencephalic parabrachial area (PBA) which includes the nucleus cuneiformis, lateral periaqueductal gray matter, and the region between the inferior colliculus and brachium conjunctivum. 2. Neurons were categorized based on their responses to non-noxious and noxious mechanical and heat stimuli delivered to their peripheral receptive fields (RFs) including skin, mucosa, guard hairs, vibrissae, cornea, and tooth pulps. They were classified into three types: 48 nociceptive-specific (NS) neurons which responded to heavy pressure and/or noxious mechanical stimuli, and/or noxious radiant heat; 19 wide dynamic range (WDR) neurons which had a graded response to light tactile stimuli, noxious pinch, and/or noxious radiant heat; and 36 low-threshold mechanoreceptive (LTM) neurons which responded maximally to innocuous tactile stimuli. In subnucleus caudalis (Vc), NS and WDR neurons were the majority (75%) among the three types, while in the rostral subnuclei they were about one-half (54%) of the population. 3. The RFs were distributed over the orofacial and head region but mainly in the facial region. Twelve neurons (33% of the LTM neurons) responded to deflection of vibrissae and only 1 NS neuron out of 52 NS and WDR neurons tested responded to electrical stimulation of a tooth pulp. 4. A contralateral projection was dominant (57%), 30% projected ipsilaterally and 13% projected bilaterally.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vivo and in vitro effects of peripheral galanin on nociceptive transmission in naive and neuropathic states

Galanin is widely distributed in the nervous system and is consistently upregulated in both dorsal root ganglion and spinal neurones by peripheral nerve injury. This study investigates the peripheral effects of galanin on nociceptive neurones using in vitro and in vivo electrophysiological techniques in naive and neuropathic rats. Using an in vitro skin-nerve preparation recording from single nociceptive fibres, galanin (1 microM) significantly inhibited firing induced by noxious heat in 65% of fibres examined. In the remaining 35% of fibres, galanin (1 microM) induced a facilitation of the responses to noxious heat. To examine the effect of peripheral galanin in vivo, extracellular recordings from convergent dorsal horn neurones were made in anaesthetised naive sham-operated and spinal nerve-ligated (SNL) rats. Injection of galanin (0.1-10 microg) into hindpaw receptive fields inhibited responses to innocuous mechanical, noxious mechanical and noxious heat stimuli in a proportion of neurones in each animal group and facilitated the remaining neurones. However, a higher proportion of neurones (80-90%) was inhibited by peripheral galanin administration in SNL rats compared with naive (45-55%) and sham (70-80%) rats. These results show that galanin can have both excitatory and inhibitory effects on peripheral sensory neurones, perhaps reflecting differential receptor activation, and that the proportion of these receptors may change following peripheral neuropathy.     

Nociceptive input to ascending tract neurones forwarding information from low threshold cutaneous and muscle afferents in cats

Effects of noxious skin stimulation (central foot pad and foot dorsum) by radiant heat were tested on neurones of ascending tracts with a main input from non-nociceptors. The dominating effect on ventral spinocerebellar tract neurones was a depression (mainly from the pad). Responses of spinocervical tract neurones were either facilitated (predominantly from the foot dorsum) or depressed (predominantly from the pad). The dominating effect on neurones tentatively classified as dorsal horn dorsal spinocerebellar tract neurones was facilitatory from both skin areas. Similar effects were evoked by selective actions of C-fibres when A-delta fibres were blocked by TTX.     

Enhanced responses of spinal dorsal horn neurons to heat and cold stimuli following mild freeze injury to the skin

The effects of a mild freeze injury to the skin on responses of nociceptive dorsal horn neurons to cold and heat stimuli were examined in anesthetized rats. Electrophysiological recordings were obtained from 72 nociceptive spinal neurons located in the superficial and deep dorsal horn. All neurons had receptive fields (RFs) on the glabrous skin of the hindpaw, and neurons were functionally divided into wide dynamic range (WDR) and high-threshold (HT) neurons. Forty-four neurons (61%) were classified as WDR and responded to both innocuous and noxious mechanical stimuli (mean mechanical threshold of 12.8 +/- 1.6 mN). Twenty-eight neurons (39%) were classified as HT and were excited only by noxious mechanical stimuli (mean mechanical threshold of 154.2 +/- 18.3 mN). Neurons were characterized for their sensitivity heat (35 to 51 degrees C) and cold (28 to -12 degrees C) stimuli applied to their RF. Among WDR neurons, 86% were excited by both noxious heat and cold stimuli, while 14% responded only to heat. For HT neurons, 61% responded to heat and cold stimuli, 32% responded only to noxious heat, and 7% responded only to noxious cold. Effects of a mild freeze injury (-15 degrees C applied to the RF for 20 s) on responses to heat and cold stimuli were examined in 30 WDR and 22 HT neurons. Skin freezing was verified as an abrupt increase in skin temperature at the site of injury due to the exothermic reaction associated with crystallization. Freezing produced a decrease in response thresholds to heat and cold stimuli in most WDR and HT neurons. WDR and HT neurons exhibited a mean decrease in response threshold for cold of 9.0 +/- 1.3 degrees C and 10.0 +/- 1.6 degrees C, respectively. Mean response thresholds for heat decreased 4.0 +/- 0.4 degrees C and 4.3 +/- 1.3 degrees C in WDR and HT neurons, respectively. In addition, responses to suprathreshold cold and heat stimuli increased. WDR and HT neurons exhibited an 89% and a 192% increase in response across all cold stimuli, and a 93 and 92% increase in responses evoked across all heat stimuli, respectively. Our results demonstrate that many spinal neurons encode intensity of noxious cold as well as noxious heat over a broad range of stimulus temperatures. Enhanced responses of WDR and HT neurons to cold and heat stimuli after a mild freeze injury is likely to contribute to thermal hyperalgesia following a similar freeze injury in humans.     

Catecholaminergic mechanisms underlying neurohypophysial hormone responses to unconditioned or conditioned aversive stimuli in rats

Oxytocin release from the neurohypophysis is facilitated by systemic cholecystokinin octapeptide (CCK) administration and noxious stimuli. Oxytocin release after CCK administration is mediated by A2 noradrenergic neurones while the release after noxious stimuli appears to be mediated by A1 noradrenergic neurones. On the other hand, facilitation of vasopressin release after noxious stimuli is not dependent upon noradrenergic neurones but on dopamine receptors. Environmental stimuli previously paired with noxious stimuli (conditioned fear stimuli) or novel environmental stimuli facilitate oxytocin release and suppress vasopressin release. These neuroendocrine responses to conditioned fear stimuli, but not to novel stimuli, are impaired by central noradrenaline depletion or i.c.v. adrenoceptor antagonists. These data suggest that there are at least two types of stress responses in neuroendocrine systems, one noradrenaline dependent, and one noradrenaline independent. It is also suggested that noradrenergic neurones are functionally heterogeneous in the control of oxytocin release.     

Maturational changes in the thermal nociceptive responses of developing rats

Some find developmental differences in rodent thermal nociceptive responses and others do not. To address these inconsistencies, the escape latencies of immature (5- to 25-day-old) and adult (3- to 4-month-old) albino rats were recorded following tail exposure to different intensities of radiant heat (650-W halogen lamp placed 10–30 mm from the tail) or conductive heat (35–50°C water). Developmental differences in tail flick latencies were not observed in immature rats when the lamp was closest to the tail (although adult latencies were longer than 5- and 15-day-old responses). When radiant heat intensity was reduced, 5-day-old rats had shorter escape latencies than 15-, 25-, and 90-day-old animals. Age differences persisted in the latencies of immature animals even when the test aperture was varied to compensate for maturational changes in tail width (whereas adult responses no longer differed from those of 5- and 15-day-old rats). Developmental differences were eliminated when the tail skin was blackened so as to normalize the absorption of radiant heat across age. Similar age- and intensity-dependent differences were observed in rats exposed to conductive heat: Five- and 10-day-old pups had shorter escape responses than older rats when tails were immersed in intermediate (40 or 45°C) but not lower (35°C) or higher (50°C) temperature water. Blackening the tails did not change conductive heat escape latencies. No sex differences were found at any age or stimulus intensity with either type of heat. Higher intensities of thermal stimuli applied to the tail are required to elicit escape responses in older rats compared to younger ones, but the use of relatively intense thermal test stimuli can mask age-dependent differences in nociception. Some of the inconsistent results reported previously about maturational changes in thermal nociception may be due to intensity differences in the noxious test stimuli used. Maturational differences in the radiant absorption properties of the tail seem to account for most of the age-related changes in rodent responses to radiant heat, but the mechanism(s) which subserve developmental differences in conductive heat nociception need to be elucidated. © 1998 John Wiley & Sons, Inc. Dev Psychobiol 33: 47–60, 1998     

Physiological properties of the lamina I spinoparabrachial neurons in the rat

Single-unit extracellular recordings of spino-parabrachial (spino-PB) neurons (n = 53) antidromically driven from the contralateral parabrachial (PB) area were performed in the lumbar cord in anesthetized rats. All the spino-PB neurons were located in the lamina I of the dorsal horn. Their axons exhibited conduction velocities between 2.8 and 27.8 m/s, in the thin myelinated fibers range. They had an extremely low spontaneous activity (median = 0. 064 Hz) and a small excitatory receptive field (相似文献   

Nociceptive responsiveness during slow-wave sleep and waking in the rat

Brainstem neurons that are thought to modulate pain are reported to have state-dependent discharge rates. Yet, the effect of behavioral state upon nociceptive transmission has not been well studied. Therefore, we examined responses to noxious thermal stimulation of the rat hindpaw presented during different behavioral states. Noxious thermal stimuli were applied to rats as they spontaneously cycled through waking and sleeping states. Two different methods of heating the paw - a focused light bulb ("radiant heat") and a CO2 laser ("laser heat")-were employed. Regardless of the heating method used, rats withdrew from noxious thermal stimulation when it was applied in each behavioral state tested. When rats were tested with radiant heat, the withdrawal latency from noxious heat was shorter during slow-wave sleep than during waking. In contrast, when tested with laser heat, there was no difference in either the response latency or magnitude evoked by noxious heat across sleep/wake states. Despite the fact that rats withdrew from noxious heat (using either method of application) applied during sleep, the rats quickly returned to sleep afterwards. The latency to sleep after noxious stimulation was significantly greater during waking than during sleeping. The behavioral response to noxious thermal stimulation includes both an initial motor withdrawal which is enhanced during sleep and arousal or alerting which is suppressed during sleep. Therefore, pain evokes at least two distinct reactions that are differentially modulated across sleep/wake cycles.     

Raphe magnus neurons help protect reactions to visceral pain from interruption by cutaneous pain

Suppression of reactions to one noxious stimulus by a spatially distant noxious stimulus is termed heterotopic antinociception. In lightly anesthetized rats, a noxious visceral stimulus, colorectal distension (CRD), suppressed motor withdrawals but not blood pressure or heart rate changes evoked by noxious hindpaw heat. Microinjection of muscimol, a GABA(A) receptor agonist, into raphe magnus (RM) reduced CRD-evoked suppression of withdrawals, evidence that RM neurons contribute to this heterotopic antinociception. To understand how brain stem neurons contribute to heterotopic antinociception, RM neurons were recorded during CRD-elicited suppression of hindpaw withdrawals. Although subsets of RM neurons that were excited (on cells) or inhibited (off cells) by noxious cutaneous stimulation were either excited or inhibited by CRD, on cells were inhibited and off cells excited by an intracerebroventricularly administered opioid, evidence that the nociception-facilitating and -inhibiting functions of on and off cells, respectively, are predicted by the cellular response to noxious cutaneous stimulation alone and not by the response to CRD. When recorded during CRD-elicited antinociception, RM cell discharge resembled the pattern observed in response to CRD stimulation alone. However, when hindpaw withdrawal suppression was incomplete, RM cell discharge resembled the pattern observed in response to heat alone. We propose that on cells excited by CRD facilitate responses to CRD itself, which in turn augments excitation of off cells that then act to suppress cutaneous nociception. RM cells may thereby contribute to the dominance of quiet recuperative reactions evoked by potentially life-threatening visceral stimuli over transient somatomotor activity elicited by less-injurious noxious cutaneous stimuli.     

Nociceptive responses of midbrain dopaminergic neurones are modulated by the superior colliculus in the rat

Midbrain dopaminergic neurones exhibit a short-latency phasic response to unexpected, biologically salient stimuli. In the rat, the superior colliculus is critical for relaying short-latency visual information to dopaminergic neurones. Since both collicular and dopaminergic neurones are also responsive to noxious stimuli, we examined whether the superior colliculus plays a more general role in the transmission of short-latency sensory information to the ventral midbrain. We therefore tested whether the superior colliculus is a critical relay for nociceptive input to midbrain dopaminergic neurones. Simultaneous recordings were made from collicular and dopaminergic neurones in the anesthetized rat, during the application of noxious stimuli (footshock). Most collicular neurones exhibited a short-latency, short duration excitation to footshock. The majority of dopaminergic neurones (92/110; 84%) also showed a short-latency phasic response to the stimulus. Of these, 79/92 (86%) responded with an initial inhibition and the remaining 14/92 (14%) responded with an excitation. Response latencies of dopaminergic neurones were reliably longer than those of collicular neurones. Tonic suppression of collicular activity by an intracollicular injection of the local anesthetic lidocaine reduced the latency, increased the duration but reduced the magnitude of the phasic inhibitory dopaminergic response. These changes were accompanied by a decrease in the baseline firing rate of dopaminergic neurones. Activation of the superior colliculus by the local injections of the GABA(A) antagonist bicuculline also reduced the latency of inhibitory nociceptive responses of dopaminergic neurones, which was accompanied by an increased in baseline dopaminergic firing. Aspiration of the ipsilateral superior colliculus failed to alter the nociceptive response characteristics of dopaminergic neurones although fewer nociceptive neurones were encountered after the lesions. Together these results suggest that the superior colliculus can modulate both the baseline activity of dopaminergic neurones and their phasic responses to noxious events. However, the superior colliculus is unlikely to be the primary source of nociceptive sensory input to the ventral midbrain.     

Lack of effect by substance P at sites in the substantia gelatinosa where Met-enkephalin reduces the transmission of nociceptive impulses.

In alpha-chloralose anaesthetized spinal cats, Met-enkephalin amide (M-ENKA) and substance P were administered electrophoretically in the substantia gelatinosa while studying the excitation of deeper spinal neurones by noxious and non-noxious cutaneous stimuli. At sites where Met-enkephalin selectively reduced excitation by noxious skin stimuli, substance P was without effect. This result does not support the hypothesis that enkephalins are released at axo-axonic synapses on the terminals of substance P releasing primary afferent fibres.     

Nucleus centralis of the amygdala and the globus pallidus ventralis: electrophysiological evidence for an involvement in pain processes.

1. Neurons (n = 177) were recorded with extracellular micropipettes in and around the nucleus centralis of the amygdala (Ce), in anesthetized rats. The spontaneous activity of these neurons was variable (0.25 less than 3 less than 35 Hz, n = 175; 10th percentile less than median less than 90th percentile). A majority (80%) of these neurons were excited or inhibited exclusively or preferentially by noxious stimuli. These units were separated into two groups: 1) a group of neurons excited by noxious stimuli (46% of the whole population) and 2) a group of neurons inhibited by noxious stimuli (34% of the whole population). 2. The receptive fields of both groups of neurons were very large: in about one-half the cases the neurons responded similarly from all parts of the body, and in the other cases the responses were greater when the stimuli were applied to a restricted part of the body. 3. Seventy-seven percent of the excited neurons had responses of relatively high magnitudes. In this group, most cells (75%) were exclusively driven by noxious stimuli; the others (25%) were preferentially activated by noxious stimuli. These neurons responded to mechanical (pinch or squeeze) and/or thermal (water bath or water jet greater than 44 degrees C) noxious stimuli with a marked and sustained activation. 4. Sixty percent of the inhibited neurons had a marked decrease of activity in response to noxious stimuli. In this group, most of them (81%) were exclusively inhibited by noxious stimuli, whereas the remainder (19%) were preferentially inhibited by noxious stimuli. These neurons responded to mechanical (pinch or squeeze) and/or thermal (water bath or waterjet greater than 44 degrees C) noxious stimuli with a suppression or a marked and sustained decrease in activity. 5. All of the nociceptive neurons responded to intense transcutaneous electrical stimulation with one or several components of activation or inhibition. According to their latencies, three types of components were distinguished: early, intermediate, and late components. We estimate that the early and the intermediate components would be triggered by the activity of peripheral fibers in the 6- to 20-m/s range and therefore could be in the A delta fibers range, whereas the late component would be triggered by fibers in the 0.5- to 1-m/s range and therefore could be in the C fibers range. 6. The neurons excited or inhibited by noxious stimuli were not homogeneously distributed in and around the Ce.(ABSTRACT TRUNCATED AT 400 WORDS)     

The time course and specificity of the changes in the behavioural and dorsal horn cell responses to noxious stimuli following peripheral nerve capsaicin treatment in the rat

Capsaicin, a neurotoxin which acts specifically on sensory primary afferent C-fibres was applied locally to one sciatic nerve of a group of rats. One to sixteen days following this a series of behavioural and electrophysiological studies were performed. The latency of foot withdrawal of the rats to a controlled thermal noxious stimuli was significantly elevated (200%). The peak increase occurred on day 1 after treatment; the response then fell to a steady but elevated level for up to 16 days. Responses to noxious mechanical stimuli were unaffected by capsaicin treatment. Single unit analysis of the dorsal horn of the spinal cord showed that the number of neurones in deep laminae (4, 5 and 6) responding to a C peripheral volley was normal (60%) for the first 2 days after treatment. On day 3 post treatment, the number of cells with a C input began to fall reaching a maximal decrease on day 7 (25%), where it remained up to day 16. In contrast to this delayed effect on C-evoked responses, the number of cells responding to noxious heating of the skin fell from control levels of 60% down to 20% on day 1 and remained decreased for up to 16 days. The onset of thermal analgesia following local, capsaicin treatment, therefore, closely parallels the time course of the decrease of noxious heat-evoked responses in the dorsal horn. Since at early pretreatment times, the electrically C-evoked activity is normal these effects are likely to be due to action on peripheral C-fibre nociceptors in the skin. At a later stage capsaicin also appears to act on the central terminals of fibres reducing transmission to second order dorsal horn neurones.     

Interactions between visceral and cutaneous nociception in the rat. I. Noxious cutaneous stimuli inhibit visceral nociceptive neurons and reflexes

1. Numerous studies have demonstrated that neural, behavioral, and reflex responses to a nociceptive test stimulus are inhibited by conditioning nociceptive stimuli; this inhibition has supraspinal, intraspinal, and segmental components. The general phenomenon is defined here as nocigenic inhibition. The present study of nocigenic inhibition documents that noxious cutaneous pinch and heat, used as conditioning stimuli, inhibit neuronal and reflex responses evoked by a noxious visceral stimulus, colorectal distension. 2. A total of 196 dorsal horn neurons were examined: 110 were short latency-abrupt (SL-A) neurons that were excited at short latency by colorectal distension and returned to baseline activity abruptly after termination of the distending stimulus, and 86 were short latency-sustained (SL-S) neurons that also were excited by colorectal distension at short latency, but demonstrated after-discharges for 4-240 s after termination of the distending stimulus. All SL-A and SL-S neurons studied had convergent cutaneous receptive fields. 3. The spontaneous activities of 100% of the 110 SL-A neurons tested were inhibited by greater than 25% by noxious pinch in sites distant from their convergent cutaneous receptive fields. In both anesthetized, intact, and spinalized rats, noxious conditioning pinch or noxious conditioning heat significantly reduced responses of SL-A neurons during noxious test colorectal distension. The magnitude of this nocigenic inhibition was graded with the intensity of the noxious conditioning stimulus. Noxious conditioning tail heating produced a parallel shift to the right in stimulus-response functions relating neuronal responses to the intensity of colorectal distension (20-100 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses of monkey medullary dorsal horn neurons during the detection of noxious heat stimuli

1. We examined the activity of thermally sensitive trigeminothalamic neurons and nonprojection neurons in the medullary dorsal horn (trigeminal nucleus caudalis) in three monkeys performing thermal and visual detection tasks. 2. An examination of neuronal stimulus-response functions, obtained during thermal-detection tasks in which noxious heat stimuli were applied to the face, indicated that wide-dynamic-range neurons (WDR, responsive to innocuous mechanical stimuli with greater responses to noxious mechanical stimuli) could be subclassified based on the slope values of linear regression lines. WDR1 neurons exhibited significantly greater sensitivity to noxious heat stimulation than WDR2 neurons or nociceptive-specific neurons (NS, responsive only to noxious stimuli). 3. In one behavioral task, the monkeys detected 1.0 degrees C increases in noxious heat from preceding noxious heat stimuli ranging from 44 to 48 degrees C. WDR1, WDR2, and NS neurons increased their discharge frequency as a function of the intensity of the first noxious heat temperature (T1) as well as the final temperature (T2). The responses of WDR1 neurons were greater than those produced by WDR2 or NS neurons across all the temperatures examined. The order of stimulus presentation affected the responses of WDR1 neurons to 1.0 degrees C increases in the noxious heat range but not those of WDR2 or NS neurons. 4. In a second behavioral task, the monkeys detected small increases in noxious heat (0.2-0.8 degrees C) from a first temperature of 46 degrees C. Although the responses of all three classes of neurons were monotonically related to stimulus intensity, WDR1 neurons exhibited greater sensitivity to small temperature increases than either WDR2 or NS neurons. 5. Subpopulations of all three classes of neurons exhibited responses that were independent of thermal stimulus parameters or sensory modality and that only occurred during the behavioral task. These task-related responses were time-locked to specific behavioral events associated with trial initiation and trial continuation. 6. These data provide evidence that a subpopulation of WDR neurons is the dorsal horn cell type most sensitive to small increases in noxious heat in the 45-49 degrees C temperature range and provides the most information about stimulus intensity. The findings support the view that nociceptive neurons have the capacity to precisely encode stimulus features in the noxious range and that WDR neurons are likely to participate in the monkeys' ability to perceive the intensity of such stimuli.     

Selective inhibition of responses of feline dorsal horn neurones to noxious cutaneous stimuli by tizanidine (DS103-282) and noradrenaline: involvement of alpha 2-adrenoceptors

The effects of tizanidine (DS103-282) were compared with those of noradrenaline and other adrenoceptor agonists on responses of laminae IV and V neurones in the lumbar dorsal horn to noxious and innocuous cutaneous stimuli in the anaesthetized cat. Tizanidine, noradrenaline and the alpha 2-receptor agonist, clonidine, depressed spontaneous activity and responses to noxious, but not those to innocuous, stimuli when administered iontophoretically, either near the recording site in laminae IV-V, or into laminae II-III, i.e. 300-900 microns dorsal to the recording site. Iontophoretic ejection of dopamine, the beta-agonist isoprenaline and the alpha 1-agonists phenylephrine and amidephrine had no effect at either site, or only relatively weak and sometimes non-selective depressant actions on neuronal responses to cutaneous stimuli. The preferential depressant actions of tizanidine, noradrenaline and clonidine were antagonized by the selective alpha 2-antagonist RX781094 administered iontophoretically at the same site as the agonists, and by intravenously administered yohimbine. In contrast, the alpha 1-antagonists, prazosin and WB4101, the beta-antagonist, sotalol and opiate antagonist, naloxone did not alter the depressant actions of these agonists on laminae IV and V neurones. These findings indicate that the selective inhibitory effect of tizanidine and noradrenaline on responses of laminae IV and V neurones to noxious peripheral stimuli are mediated at alpha 2-adrenoceptors situated in either laminae IV and V or laminae II-III. The possible physiological relevance of these receptors is discussed.     

Regional intensive and temporal patterns of functional MRI activation distinguishing noxious and innocuous contact heat

Cortical responses to painful and nonpainful heat were measured using functional magnetic resonance imaging (fMRI) region of interest analysis (ROI) of primary somatosensory cortex (S1), secondary somatosensory cortex (S2), anterior cingulate (ACC), supplementary motor area (SMA), insula, and inferior frontal gyrus (IFG). Previous studies indicated that innocuous and noxious stimuli of different modalities produce responses with different time courses in S1 and S2. The aim of this study was to 1) determine whether temporally distinct nociceptive blood oxygen level-dependent (BOLD) responses are evoked in multiple somatosensory processing cortical areas and 2) whether these responses discriminate small noxious stimulus intensity differences. Thirty-three subjects underwent fMRI scanning while receiving three intensities of thermal stimuli, ranging from innocuous warm (41 degrees C) to 1 degrees C below tolerance, applied to the dorsum of the left foot. Innocuous and noxious responses were distinguishable in contralateral S1, the mid-ACC, and SMA. The peak of the nociceptive response was temporally delayed from the innocuous response peak by 6-8 s. Responses to noxious but not to innocuous stimuli were observed in contralateral posterior insula. Responses to innocuous and noxious stimuli were not statistically different in contralateral S2. In contralateral S1 only, the nociceptive response could differentiate heat stimuli separated by 1 degrees C. These results show that 1) multiple cortical areas have temporally distinguishable innocuous and noxious responses evoked by a painfully hot thermode, 2) the nociceptive processing properties vary across cortical regions, and 3) nociceptive responses in S1 discriminate between painful temperatures at a level unmatched in other cortical areas.     

Responses of reticulospinal neurons in the lateral reticular nucleus area of the rat to cutaneous noxious and non-noxious stimulation

Response properties of reticulospinal neurons in the lateral reticular nucleus (LRN) area to natural cutaneous stimulation were investigated systematically in 45 urethane-anesthetized rats by using extracellular recording techniques. A total of 64 neurons were tested with peripheral stimuli, of which 19 were responsive only to noxious stimuli; 7 responsive to both noxious and non-noxious stimuli; 4 responsive only to non-noxious stimuli; and 34 not responsive to any cutaneous stimuli. Both the noxious and non-noxious receptive fields were large and bilateral. Among the neurons responding to noxious stimuli, the majority (72%) was excited. This study provides evidence that some reticulospinal neurons in the rat LRN area are involved in the mechanisms of nociception.