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M Gautron

Publications and source records attributed to M Gautron.

At least 19 recordsLinked to original sources

Changes in neuronal activities in the two ventral posterior medial thalamic nuclei in an experimental model of trigeminal pain in the rat by constriction of one infraorbital nerve.

The present study analyzes the activity of 120 neurons recorded in the two ventro-postero-medial (VPM) nuclei of the thalamus in a rat model of trigeminal neuropathic pain. Twenty-eight rats were tested 2 weeks after a chronic constriction injury (CCI) of the infraorbital nerve (IoN). These animals exhibited violent pain-related reactions to extremely weak mechanical stimuli applied to the lesioned and, to a lesser extent, unlesioned IoN territories. The activities of neurons recorded in the VPMc (n = 80) and VPMi (n = 40), contralateral and ipsilateral to the injured nerve, respectively, were compared with those of 62 neurons recorded in the VPM of ten normal rats (VPMn). The neuronal background activity was higher in the VPM of CCI-IoN rats than in normal rats (about 4 vs 1 spike/s). The proportion of neurons which were driven by mechanical stimulations applied contralaterally to their recording site, was comparable in the three VPM (63-70%), but the effective stimulus modality differed significantly between the normal and the lesioned rats. In particular, the number of neurons driven by vibrissa or guard hair movements dramatically decreased in the VPM of CCI-IoN rats, mainly in the VPMc (67% of neurons with a receptive field (RF) in the VPMn vs 12% in the VPMc). Inversely, a consistent number of neurons in both the VPMc and VPMi were driven by other stimulus modalities applied to the IoN territory (moderate pressure for VPMc neurons, pinch or pinprick for both VPMc and VPMi neurons). The responses so induced were especially intense and included afterdischarges. In contrast to the VPMn neurons, the RFs of both the VPMc and VPMi neurons included two vibrissae at least, and were occasionally discontinuous and multimodal, including both vibrissae and cutaneous areas for VPMc units. The bilateral changes in VPM responsiveness and in behavior suggest the involvement of central processing of sensory information, which are set off by the CCI-IoN. The putative mechanisms and functional implication of the changes in the VPM neuronal activities are discussed.

Animals↗

Experimental model of trigeminal pain in the rat by constriction of one infraorbital nerve: changes in neuronal activities in the somatosensory cortices corresponding to the infraorbital nerve.

Neuronal activities of the somatosensory (Sm1) vibrissa cortex were explored bilaterally under moderate gaseous anaesthesia in rats with a chronic constriction injury (CCI) of an infraorbital nerve (IoN). The CCI-IoN rats exhibited abnormal pain-related reactions to mechanical stimuli directed to the territory of the injured nerve, just prior to the recording session. The responsiveness, laminar localisation, and somatotopic organisation of 388 neurones were recorded in the pad vibrissa cortex contralateral (Cc, n=249) and ipsilateral (Ci, n=139) to the injured nerve, analysed, and compared with 223 neurones recorded in a parallel study of the Sm1 cortex in normal rats (Cn). The mean background activity of all the recorded neurones was relatively low, whether they were located in the Cn, Cc or Ci. The responsive neurones occurred in similar proportions in the Cc and Ci (approximately 55%) and significantly more frequently than in the Cn (35%). They consisted mainly of vibrissa neurones (100% in Cn, 85% in Cc, and 93% in Ci). The ratio [vibrissa neurones/(vibrissa+unresponsive) neurones] was enhanced in all the cortical layers of the Cc and Ci, except in the Cc layer IV. The receptive field (RF) size of the vibrissa neurones also differed greatly. It was limited to one vibrissa for 88% of the Cn neurones, but expanded to two or more vibrissae for 72% of the Cc and 52% of the Ci neurones. These multivibrissa units, mostly located in layers V and VIa for the few Cn neurones, were scattered in the different layers in CCI-IoN rats, with the largest RFs occurring in the deepest layers. In parallel, the cortical somatotopy of the vibrissae, roughly comparable with that initially described in pioneer studies of normal rats, was dramatically disturbed not only in the Cc, but also in the Ci of CCI-IoN rats. Contrasting with the results previously obtained in the ventro-postero-median thalamic nucleus of CCI-IoN rats, no neurones were driven by pinches or pinpricks applied to the cutaneous part of the vibrissa pad. It is questioned whether the disorganisation within the cortical map of the whisker pad, and the expanded RFs of vibrissa neurones could account for the abnormal pain-related reactions elicited from the massively deafferented trigeminal area.

Animals↗

Isobolographic analysis of interactions between intravenous morphine, propacetamol, and diclofenac in carrageenin-injected rats.

BACKGROUND: It has been suggested that the combination of analgesic drugs may have additive or synergistic effects. In clinical practice, this might allow better analgesia and reduction of side effects. METHODS: The effects of analgesic drugs were studied in a model of acute inflammatory pain in carrageenin-injected rats using the vocalization threshold to paw pressure. A combination of three different intravenous drugs were used: morphine, diclofenac, and propacetamol, a pro-drug of acetaminophen. The dose-response curves were first obtained for each drug alone. The analgesic potencies of the combinations of morphine and diclofenac (ratios, 1:5.66 and 1:10), morphine and propacetamol (ratio, 1:250), and diclofenac and propacetamol (ratio, 1:65.7) were thereafter evaluated and compared with the effects of the drugs alone. RESULTS: For the two different ratios tested, synergy between diclofenac and morphine was observed only with the higher doses. Propacetamol and morphine or diclofenac and propacetamol combinations were additive for all doses tested. CONCLUSIONS: This study found a synergy between intravenous morphine and diclofenac that is consistent with and helps explain the clinical value of this type of combination in the treatment of acute pain in humans.

Acetaminophen↗

Estrous and sex variations in vocalization thresholds to hindpaw and tail pressure stimulation in the rat.

This study examined sex and estrous differences in vocalization thresholds of rats to hindpaw and tail pressure stimulation tested daily throughout at least 3 weeks. When all the measures were pooled, compared to males, female rats had higher thresholds for tail pressure (499 +/- 6 g, n = 188 measures vs. 466 +/- 2 g, n = 144 measures, respectively), but equal thresholds for hindpaw pressure (321 +/- 6 g, n = 188 measures vs. 319 +/- 2 g, n = 144 measures, respectively). Thresholds of female rats in proestrus and estrus were lower than those of rats in metestrus and diestrus for both tail and hindpaw stimulation, whereas those of males did not vary systematically. Thresholds at the two stimulation sites covaried in females but not in males. These results add to the growing list of important interacting factors that underly behavioral sensitivity to noxious somatic stimulation.

Animals↗

Responses of neurons in the caudal intralaminar thalamic complex of the rat to stimulation of the uterus, vagina, cervix, colon and skin.

This study examined responses of 35 neurons in the caudal intralaminar (IL) thalamic nuclei in 12 adult female virgin rats to mechanical stimulation of the skin (brush, pressure, pinch) and to 4 different visceral stimuli (noxious distension of the uterine horns and vaginal canal; gentle distension of the colon and probing the cervix). As in male rats and other species, many IL neurons (24/35) responded to frankly noxious somatic stimuli applied to several bodily regions. Some of these (16/24) also responded to one or more of the visceral stimuli (mainly the noxious ones), while 4/35 responded only to a visceral stimulus. Thus, unlike neurons in lateral thalamus studied under identical conditions, IL neurons appear to be signalling information primarily when intense somatic and visceral stimuli are frankly above the noxious threshold.

Animals↗

Contribution of the sciatic and saphenous nerve to the ventrobasal thalamic neuronal responses to pinch in rats with a chronic sciatic nerve constriction: a study using anesthetic blocks and nerve section.

To extend the study on the respective contribution of the sciatic and saphenous nerve in abnormal nociceptive responses observed in rats with a loose constriction of one sciatic nerve, neuronal responses to pinch applied to the territory of the injured nerve, recorded in the ventrobasal complex of the thalamus have been studied. Eleven neurones recorded in 11 rats with a nerve constriction since 15-19 days and clear abnormal pain-related behaviour to mechanical stimulus, were tested before and during an anesthetic block of the saphenous and/or of the sciatic nerve, and/or after the saphenous nerve section. Only the sciatic nerve block depressed significantly the pinch responses.

Anesthetics↗

Responses of neurons in thalamic ventrobasal complex of rats to graded distension of uterus and vagina and to uterine suprafusion with bradykinin and prostaglandin F2 alpha.

This study examined the responses of somatic-responsive neurons in and near the ventrobasal complex (VB) of halothane/nitrous oxide-anesthetized and paralyzed estrous virgin rats to increasing levels of distension of the uterine horn and vaginal canal and to uterine suprafusion with PGF2 alpha and bradykinin (BK). While individual responses of single neurons to uterine and vaginal distensions were idiosyncratic, as a group the neurons responded in a graded fashion to graded distensions, producing stimulus-responses functions nearly identical to those produced by conscious rats making escape responses to the same stimuli [Berkley and Wood, Soc. Neurosci, Abstr., 15 (1989) 979; Berkley et al., Soc. Neurosci. Abstr., 16 (1990) 416]. In addition, most neurons responded vigorously to PGF2 alpha and BK, with responses to BK but not PGF2 alpha, reliably preceding the 'giant' uterine contractions that were also produced by these algogenic agents. These results indicate that certain neurons in and near VB may as a group be involved in some aspect of pain arising from female reproductive organs. The responses of these neurons to somatic and possibly other visceral stimuli, however, point to their potential additional involvement in other aspects of visceral and somatic nociception.

Animals↗

Time course of degeneration and regeneration of myelinated nerve fibres following chronic loose ligatures of the rat sciatic nerve: can nerve lesions be linked to the abnormal pain-related behaviours?

This study of a mononeuropathy of 1-15 weeks (W) duration was induced in rats by setting 4 loose ligatures around the common sciatic nerve. This chronic lesion, in which the continuity of the nerve was maintained, has been introduced as a model for experimental pain. Quantitative analyses of teased nerve fibres and a morphometric analysis of semi-thin transverse sections, were performed and completed by electron microscopic examination. Morphological changes were observed mainly distal, but also proximal, to the ligatures, indicating significant axonopathy with simultaneous degeneration and regeneration. The lesions were analysed in parallel with the time course of the pain-related behaviours. Both were at their maximum 2 weeks after ligature with progressive recovery beginning between W3 and W4. However, the largest fibres had not totally recovered by W15, contrasting with the disappearance of abnormal nociceptive reactions between W8 and W10. Although the damage to unmyelinated fibres is of importance, the abnormal pain-related behaviours seen in these rats appeared to be closely linked to the presence of both degenerative and regenerative changes in the A delta-range fibres, which did not necessarily correspond to initial A delta fibres.

Animals↗

Responses of neurons in and near the thalamic ventrobasal complex of the rat to stimulation of uterus, cervix, vagina, colon, and skin.

1. Previous studies in the rat and other species have shown that neurons in and near the ventrobasal complex (VB) can be activated by various visceral as well as somatic stimuli. 2. This study examined the responses of 84 single neurons in and near the rostral 2/3 of VB in 19 adult female rats in estrus to mechanical stimulation of the skin (brush, pressure, noxious pinch) and 4 different visceral stimuli, as follows: distension of both uterine horns, mechanical probing of the vagina, gentle pressure against the cervix, and distension of the colon. The rats were studied while under moderate gaseous anesthesia (33% O2-67% N2O + 0.5% halothane) and paralyzed (pancuronium bromide). 3. Of 77 neurons tested with both somatic and visceral stimuli, 70 were responsive to one type and/or the other. Responses to somatic stimuli were immediate with brief afterdischarges to the pinch stimuli. In contrast, responses to visceral stimuli were delayed an average of 9 s with long afterdischarges averaging 2 min. Most viscerally responsive neurons (74%) had somatic receptive fields, often (44%) to noxious pinch. 4. Of the 70 responsive neurons, 43 (61%) responded to 1 or more of the 4 visceral stimuli, primarily with excitation. Most of these 43 neurons (71%) were responsive to uterine distension, whereas fewer responded to stimulation of the cervix (45%), vagina (29%), or colon (34%). 5. Viscerally responsive neurons were preferentially located in regions bordering or near VB. Only 6 of 22 neurons within the core of VB (27%) responded to visceral stimuli, in contrast with 37 of 48 neurons bordering or near VB (77%). 6. The six viscerally responsive neurons within VB all had somatic receptive fields located primarily on the caudal part of the body and were responsive to only one or two of the four visceral stimuli, usually the uterus. The 37 viscerally responsive neurons bordering or near VB were of 3 types. Neurons of the first type (n = 15) were scattered throughout the areas bordering VB and responded to both somatic and visceral stimuli much like VB neurons, except that they showed more visceral convergence. Neurons of the second type (n = 11) were concentrated at the rostral and dorsal borders of VB and responded only to visceral stimuli, mainly the uterus. Neurons of the third type (n = 11) were concentrated ventrally and had very complex, long-lasting and history-dependent response characteristics to both visceral and somatic stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Further evidence for the involvement of SmI cortical neurons in nociception: their responsiveness at 24 hr after carrageenin-induced hyperalgesic inflammation in the rat.

In this electrophysiological study, the responsiveness of neurons in the primary somatosensory cortex (SmI) was analyzed in rats with carrageenin-induced hyperalgesia for 24 hr. The functional implication of some changes in neuronal activity was improved in a few cases by a pharmacological test with Xylocaine injection in or close to the neuronal receptive field (RF), or with systemic aspirin. Unit recordings were performed alternately in the SmI cortex contralateral (Cc) or ipsilateral (Ci) to the inflamed hindpaw. In 29 rats with hyperalgesia tested prior to the recording session, 218 cells (128 in the Cc, 90 in the Ci) were tested with mechanical stimuli. In each SmI cortex, about 50% of them were driven by the stimulus. The "nonresponsive" neurons exhibited a higher firing rate in the Cc than in the Ci. The "responsive" (i.e., the somatosensory) neurons were classified according to their response to light touch, pinch, or joint movement. There was a highly significant difference between the two cortices, essentially because of the high proportion of "joint" Cc neurons (27 of 73 [37%] of the somatosensory neurons in the Cc, vs. only 8 of 47 [17%] in the Ci). "Light touch" neurons (41 of 73 [56%] in the Cc, vs. 35 of 47 [74.5%] in the Ci) had small RFs contralateral to the recording site. Of the 41 Cc cells of this type, 23 did not exhibit the classical characteristics of "light touch" cells; in particular, they exhibited striking discharges triggered by the stimulus but outlasting the stimulus duration, or occurring without intentional stimulation. These abnormal discharges were depressed or suppressed by injection of a local anesthetic (Xylocaine) in or close to the neuronal RF. "Pinch" neurons were very rare (5 of 73 [7%] in the Cc, vs. 4 of 47 [8.5%] in the Ci). Responses elicited from the inflamed paw were more pronounced than those from the noninflamed paw. "Joint" neurons were more numerous in the Cc than in the Ci. In addition, their responses obtained from contralateral RFs, and therefore from the inflamed paw, were more sustained than Ci responses elicited from the noninflamed paw. Afterdischarges of Ce neuronal responses and spontaneous paroxysmal activity were common on this side and were depressed by local anesthetic (Xylocaine) in their RFs or by systemic aspirin. These electrophysiological data emphasize the implication of SmI cortex in inflammatory hyperalgesia and more generally in pain processing.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Primary somatosensory cortex in rats with pain-related behaviours due to a peripheral mononeuropathy after moderate ligation of one sciatic nerve: neuronal responsivity to somatic stimulation.

Single-unit recordings were made under moderate gaseous anaesthesia in the hindpaw representation area of the two primary somatosensory motor cortices (SmI) of rats (n = 58) rendered mononeuropathic by four loose ligatures placed around one common sciatic nerve 2-3 weeks beforehand. The rats exhibited clear hyperalgesia and allodynia from the paw with the ligated sciatic nerve, to both mechanical and thermal stimuli. From the tested neuronal population (n = 640), about the same proportion could be activated by somatic stimuli in each cortex: 165/362 (45%) in the cortex contralateral to the ligated sciatic nerve (Cc), 105/278 (37%) in the cortex ipsilateral to the ligated sciatic nerve (Ci). Neurones driven by light touch, exhibited RFs strictly contralateral to the recording sites. Their proportion and response characteristics were similar regardless of recording side. However, the number of neurones with RFs in the sciatic nerve territory was above 95% in the Ci, and was dramatically reduced to 43% in the Cc. By contrast, the number of neurones with RFs supplied by the saphenous nerve reached 57% on this side. Although the RF size of all the neurones appeared roughly normal, there were fewer Cc than Ci neurones with RFs located on the paw itself and with RFs of extremely small size in the sciatic nerve territory. The proportion of neurones responding to a joint stimulus was significantly higher in the Cc than in the Ci. The neuronal responses to joint stimuli of the paw with the ligated sciatic nerve were significantly more sustained than those recorded in the Ci and elicited from the normal paw. The proportion of neurones driven by mechanical stimulation which gave rise to nociceptive reactions in freely moving animals, i.e. "nociceptive" neurones, was comparable in each cortex. However, half of the Cc neurones exhibited paroxysmal discharges occurring without intentional stimulation and of long duration (1 min to several minutes). Only 66% of Cc but 93% of Ci "nociceptive" neurones were exclusively activated by pinch. The remaining Cc neurones were also activated by applying moderate pressure to the paw with the ligated nerve. Pinch responses from the paw with the ligated nerve were often more intense and of longer duration than responses elicited from the intact paw. The "nociceptive" Cc neurones were especially sensitive to thermal stimuli of 39-44 degrees C when the stimuli were applied to the paw with the ligated nerve. They also responded vigorously to a 10 degrees C stimulus applied to this paw.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Further evidence for the involvement of SmI cortical neurons in nociception: modifications of their responsiveness over the early stage of a carrageenin-induced inflammation in the rat.

In this electrophysiological study, changes in the responsiveness of neurons in the primary somatosensory (SmI) cortex in rats were analyzed during the development of carrageenin (CRG)-induced inflammation, an animal model of acute inflammatory hyperalgesia. SmI neurons were characterized as responding to non-noxious light touch, non-noxious articular movement, or noxious pinch. A total of 23 neurons so characterized in three groups were recorded for 60 min (17 of these neurons were recorded for up to 150 min) after an intraplantar injection of CRG. The possible modifications in their background and evoked activities were analyzed over this period of time. After CRG administration, cells responding to noxious pinch stimuli (n = 8) showed a nonsignificant increase in spontaneous activity, but a significant increase in their evoked response to pinch. These results were quite similar to past observations in the ventrobasal nucleus of the thalamus (VB). Cells responding to non-noxious articular stimulation (n = 6) showed variable modifications and no significant increase in the mean evoked response for up to 60 min. These results for articular cells were also quite comparable to results seen for VB responses for similar cells. However, mean spontaneous activity, which showed a highly variable increase, was significantly increased after 60 min. The depressive effect of a local anesthetic, Xylocaine, was tested on the activities of four cells (one pinch, three light touch units) 60 min after CRG administration over a 20-min interval. Xylocaine was found to depress both spontaneous activity and responses to the effective somatic stimulus, thereby implying that the observed central modifications in neuronal discharge are linked to the peripheral inflammation. Modifications observed for each group of cells are compared with past observations in peripheral fibers, in spinal dorsal horn neurons, and especially in the VB under similar inflammatory conditions. These data confirm that the SmI cortex is involved in the nociceptive process. Furthermore, the contrast between some modifications observed at this level and past observations under similar inflammatory conditions suggests a unique role of some cortical neurons, which might partially account for mechanical allodynia.

Afferent Pathways↗

Electrophysiological evidence that morphine can exert an antinociceptive effect in a neuropathic state: a study in the ventrobasal thalamus of rats after moderate ligation of one sciatic nerve.

This study was performed in rats with a mononeuropathy induced by loose ligatures around the common sciatic nerve 2 weeks before the recording session, and exhibiting clear alterations of several pain-related behaviours. Morphine injected intravenously (0.6 and 1 mg/kg) strongly depressed the ventrobasal thalamic neuronal responses to pinch applied to the lesioned or the non-lesioned hindpaw. The effect, comparable on the both sides, was dose-related and reversed by naloxone (0.1 mg/kg i.v.).

Analysis of Variance↗

The spectrum of fiber loss in a model of neuropathic pain in the rat: an electron microscopic study.

Recently, Bennett and Xie reported that when the sciatic nerve of the rat is ligated loosely, the rat develops a pain syndrome with many features similar to those observed in neuropathic pain states in man. Anatomical and physiological studies to date indicate that the major pathology is a loss of large diameter myelinated fibers distal to the ligatures, with more subtle changes in small myelinated fibers. With a view to evaluating possible changes in the unmyelinated fibers, we have performed an electron microscopic analysis of the sciatic nerve 2 weeks after four ligatures were applied, at which time the animals displayed profound hyperalgesia and mechanical and thermal allodynia. Cross-sectional photomontages of regions proximal and distal to the ligatures were studied. Consistent with light microscopic and electrophysiological studies, we found a near complete loss of large myelinated fibers distal to the ligatures. Phagocytosis of large fibers was common. There was also considerable variation in the damage to small myelinated fibers. In some fascicles many small (less than 3 microns) myelinated axons remained; in other fascicles none could be detected. Importantly, we also found significant changes in the unmyelinated fiber spectrum. Counts of unmyelinated axons revealed a 34% and 71% decrease in the distal compared to the proximal nerve, in the two rats studied. The large clusters of unmyelinated axons that characterize normal nerve (and the nerve proximal to the ligatures) were rarely found distally. Rather, many of the unmyelinated axons coursed singly or in very loose bundles. Many of the surviving axons were shrunken and distorted, although still in contact with Schwann cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Alterations in myelinated fibres in the sciatic nerve of rats after constriction: possible relationships between the presence of abnormal small myelinated fibres and pain-related behaviour.

Morphology or peripheral myelinated fibres was analyzed in rats exhibiting hyperalgesia and allodynia with mechanical and thermal stimuli, consecutive to a mononeuropathy induced by 4 loose ligatures around a sciatic nerve. This preliminary study was based on weeks 2-3 after surgery, the time of the maximum alterations of the pain-related behaviour. At this time, contrasting with a marked decrease of the large afferent fibres a consistent number of much less than 5 micron fibres was pointed out. In addition to their extremely short internodal length, the majority of these fibres had an abnormal g-ratio, thus an abnormal myelin sheath. It is suggested that this group of abnormal fibres might be related to the A delta fibres described in neuromas and involved in pain-related behaviours seen in the mononeuropathic rats.

Animals↗

Neuronal responsiveness in the ventrobasal thalamic complex of rats with an experimental peripheral mononeuropathy.

1. Single-unit recordings were made, under moderate gaseous anesthesia (33% O2-66% N2O + 0.5/0.6% halothane), in the ventrobasal (VB) thalamic complex of rats (n = 42) with a mononeuropathy created 2-3 wk beforehand, by four loose ligatures around the common sciatic nerve. Before the recording session, three behavioral nociceptive tests to both mechanical and thermal stimuli revealed that these rats exhibited clear hyperalgesia (excessive reactions to noxious stimuli) and allodynia (nociceptive reactions to stimuli usually perceived as nonnoxious). 2. Neurons, characterized by their responses to manual mechanical stimuli, were classified into two groups: group 1 neurons exclusively driven by light tactile stimuli applied to the receptive field (RF), strictly contralateral to the recording site; and group 2 neurons, driven by sustained pinch applied to a large RF, often bilateral. 3. From the total population of neurons (n = 386), only those responding to stimuli applied to one posterior paw were studied; the proportion (35-40%) of these cells was comparable in each of the two VB: n = 93/262 and 44/124 in the VB contralateral (VBc) and ipsilateral (VBi) to the damaged nerve, respectively. The proportions of each functional group of neurons (group 1 or 2) were also similar on each side. 4. For all group 1 neurons the RFs size was comparable to that observed in normal rats. In the VBi the responses of these neurons presented the classical response pattern observed for VB neurons involved in touch transmission, as did the VBc group 1 neurons with RFs in the saphenous (Sa) territory. In sharp contrast, activities of VBc group 1 neurons with RFs in the sciatic (Sc) nerve territory exhibited several abnormalities: higher background activity, fading of the response with repetitive stimulation, and afterdischarges outlasting the applied stimulus. 5. As in normal rats, 52% of VB group 2 neurons exhibited bilateral symmetrical RFs. Their responses to mechanical stimuli were often greater for stimuli applied to the affected paw, and some of them could be activated by moderate pressure to this paw. Heat responses also illustrated the profound increased sensitivity of the lesioned side, and the activation threshold to thermal stimulation of these group 2 neurons was lowered by 4-6 degrees C compared to normal values. In addition, these neurons responded to immersion of the lesioned paw in a 10 degrees C water bath, a stimulus that was ineffective when applied to the opposite paw.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evidence for peripheral serotonergic mechanisms in the early sensitization after carrageenin-induced inflammation: electrophysiological studies in the ventrobasal complex of the rat thalamus using a potent specific antagonist of peripheral 5-HT receptors.

The effect of ICS 205-930 (ICS), a specific 5-HT3 receptor antagonist, was analyzed on the sensitization of ventrobasal (VB) thalamic neuronal responses produced by an intraplantar injection of carrageenin. ICS was injected locally in the plantar paw, simultaneously, or after carrageenin (at 20 min or later than 70 min). The progressive increase of the VB neuronal responses to pinch (total number of spikes in the discharge) due to carrageenin sensitization, was prevented, blocked, or reversed, by intraplantar ICS, at a dose as low as 3.2 ng/kg, when injected, simultaneously or in the first half-hour following the carrageenin injection itself. The carrageenin sensitization then reappeared, 50-90 min after the initiation of the inflammation. By contrast to these early injections of ICS, a later administration of ICS (70 min or more, after the carrageenin injection), did not influence the sensitization. The time course of the effects of this 5-HT3 antagonist receptor agrees well with the time course of 5-HT release into the inflammatory exudate. These data, and those previously reported on the action of aspirin and of a peripheral antihistamine on carrageenin sensitization, are compared. These results indicate the relative participation of the various inflammatory substances released in the exudate, and the importance of timing of administration for an effective antagonism of the hyperalgesia elicited by this inflammation.

Action Potentials↗

Evidence for central phenomena participating in the changes of responses of ventrobasal thalamic neurons in arthritic rats.

In this study performed in the Freund's adjuvant-induced arthritic rat, a local injection of lidocaine in one hind paw strongly depressed the ventrobasal thalamic neuronal responses to mild stimulation of both ankles. In parallel, a behavioral study provided evidence for a bilateral hypoalgesia, tested by the vocalization threshold to paw pressure, after a unilateral anesthetic block. The involvement of central phenomena in the changes of neuronal responsivity described in this model of experimental pain is therefore suggested.

Action Potentials↗