Biomedical subjects

G Guilbaud

Publications and source records attributed to G Guilbaud.

At least 55 records · Page 3Linked to original sources

PubMed1993

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↗

PubMed1993

Are mechanical and cold allodynia in mononeuropathic and arthritic rats relieved by systemic treatment with calcitonin or guanethidine?

The putative antinociceptive action of guanethidine and calcitonin systemically injected has been compared in 2 rat models of persistent experimental pain: Freund's adjuvant-induced arthritis (n = 29) and mononeuropathy induced by 4 loose ligatures around the sciatic nerve (n = 24). Guanethidine (30 mg/kg, i.v.) and calcitonin (0.125 mg, s.c.) were injected once a day over 1 week, when hyperalgesia was fully developed. The antinociceptive action was gauged using nociceptive tests based on mechanical or cold stimuli (vocalization threshold to paw pressure and struggle latency to 10 degrees C, respectively), and the score of spontaneous pain-related behavior was measured on the basis of the abnormal hind paw position. No antinociceptive action was observed in calcitonin-compared to saline-injected rats, either in arthritic or neuropathic animals. Guanethidine treatment was ineffective on hyperalgesia exhibited in arthritic rats but was able to reduce reliably and even suppress the abnormal reactions to cold stimulus in neuropathic animals. The lack of hypoalgesic action of calcitonin versus its beneficial action in bone repair, as well as the possible role(s) of the sympathetic system in neuropathic versus arthritic pain and in hyperalgesia versus physical signs of inflammation, are discussed.

Animals↗

PubMed1993

Selective opioid receptor agonists modulate mechanical allodynia in an animal model of neuropathic pain.

This study evaluated the antinociceptive effects of systemically administered selective opioid agonists of mu (DAMGO), delta (BUBU) and kappa (U 69593) receptors on the vocalization threshold to paw pressure in a rat model of peripheral unilateral mononeuropathy produced by loose ligatures around the common sciatic nerve. DAMGO (0.5-2 mg/kg), BUBU (1.5-6 mg/kg) and U 69593 (0.75-3 mg/kg) injected intravenously (i.v.) produced a potent long-lasting antinociceptive effect on both hind paws. The effects on the lesioned paw were clearly and statistically more potent than for the non-lesioned paw. The selective antinociceptive effect of 2 mg/kg DAMGO, 3 mg/kg BUBU and 1.5 mg/kg U 69593 were completely prevented by prior administration of the appropriate antagonists: 0.1 mg/kg naloxone, 1 mg/kg naltrindole and 0.4 mg/kg MR 2266. The present data clearly show that an acute i.v. injection of these selective opioid agonists induces potent antinociceptive effects in a rat model of peripheral neuropathy. These data are discussed with regard to the classical view that there is opioid resistance in neuropathic pain.

Analgesics↗

PubMed1993

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↗

PubMed1993

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↗

PubMed1992

Evidence for a noradrenergic component in the antinociceptive effect of the analgesic agent tramadol in an animal model of clinical pain, the arthritic rat.

The analgesic agent tramadol has a potent antinociceptive effect in arthritic rats. In the present study, the actions of the selective alpha 2-adrenoceptor antagonists yohimbine and idazoxan on this antinociceptive effect were tested in arthritic rats, using vocalization thresholds to paw pressure as a nociceptive test. The antagonists were administered 30 min before tramadol, at doses (0.5 and 1 mg/kg i.v.) without action per se, but which prevented the antinociceptive action of the prototypic alpha 2-adrenoceptor agonist clonidine (0.1 mg/kg i.v.) in these animals. The potent antinociceptive effect of tramadol (1 mg/kg i.v.) was significantly decreased (mean total effect reduced about 2-fold) by yohimbine and idazoxan. In alpha 2-adrenoceptor antagonists-pretreated arthritic rats, the effect of tramadol was almost abolished when tramadol was coinjected with the opioid antagonist naloxone. In addition to the involvement of opioid receptors, these results provide evidence for a noradrenergic component to the antinociceptive action of tramadol in this model of clinical pain.

Adrenergic alpha-Agonists↗

PubMed1992

Potent antinociceptive effects of clonidine systemically administered in an experimental model of clinical pain, the arthritic rat.

The effects of various doses of the alpha-2 adrenoceptor agonist clonidine administered systemically (30, 50 and 100 micrograms/kg i.v.), were investigated on the vocalization threshold to paw pressure in normal rats and in rats with Freund's adjuvant-induced arthritis. Previous results have suggested that there is an increase in the activity of the bulbospinal noradrenergic systems in these arthritic animals. In the present study, clonidine led to significant antinociceptive effects in both groups of rats. Clonidine was found to be highly effective in arthritic animals, even at the lower concentration: the elevation in threshold produced by 30 micrograms/kg i.v. was 160% in arthritic vs. 124% in normal rats. The effects of clonidine were prevented dose-dependently by pretreatment with yohimbine or idazoxan 250 to 1000 micrograms/kg i.v., in the two groups of rats, indicating clearly that the dose-dependent effects of i.v. clonidine are mediated by alpha-2 adrenoceptors.

Adrenergic beta-Antagonists↗

PubMed1992

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↗

PubMed1992

Antinociceptive effects of acute and 'chronic' injections of tricyclic antidepressant drugs in a new model of mononeuropathy in rats.

The tricyclic antidepressant drugs (TCAs) are commonly used in the treatment of chronic, especially neuropathic, pain. We evaluated their possible effect on a new model of neuropathic pain-related behaviour induced by ligatures tied loosely around the common sciatic nerve. The effects of 3 TCAs with different monoaminergic spectra (clomipramine, amitriptyline and desipramine) were assessed 2 weeks after surgery, the time of the maximum hyperalgesia, on a 'phasic' test (vocalization threshold to paw pressure) and on a 'tonic' test (score of the spontaneous pain-related behaviour). TCAs were acutely (0.5 and 2 mg/kg, i.v.) and 'chronically' injected (7 injections, once every half-life of the drug: 0.75 and 1.5 mg/kg, s.c., for clomipramine and 1.5 and 3 mg/kg, s.c., for amitriptyline and desipramine). Acutely injected clomipramine and amitriptyline (0.5 mg/kg, i.v.) and desipramine (2 mg/kg, i.v.) showed an antinociceptive naloxone-reversible effect, assessed by an increase in the vocalization threshold to the paw pressure test and, for amitriptyline, by a decrease in tonic pain scores. Chronically injected TCAs induced a significant and progressive increase in the vocalization threshold with a time course parallel to that of their suspected plasma or nerve tissue levels: (i) a regular increase of scores for the first 3-4 injections, (ii) then a plateau until the last injection, and (iii) a progressive decrease with a dose-dependent duration of the effect, longer than that obtained with a corresponding acute dose. This study showed that in this new model of mononeuropathy, acutely and chronically injected TCAs induce an antinociceptive effect and suggested that their analgesic action could be related to the monoaminergic spectrum of the drug in relation to the opiate systems.

Animals↗

PubMed1992

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↗

PubMed1991

Physiological relevance and time course of a tonic endogenous opioid modulation of nociceptive messages, based on the effects of naloxone in a rat model of localized hyperalgesic inflammation.

In a rat model of localized hyperalgesic inflammation induced by intraplantar injection of carrageenin, the effect of a relatively high dose of naloxone (1 mg/kg i.v.) was investigated using the measure of the vocalization threshold as a nociceptive test, on both the inflamed and non-inflamed paws. The effects of the drug were determined at two different periods after the intraplantar injection of carrageenin, in the same group of rats. We showed that 4 h after carrageenin (a few hours after the onset of the inflammatory process), naloxone induced a significant further decrease in the vocalization threshold induced by pressure on either paw, suggesting that naloxone had reduced a tonically active inhibitory system involving endogenous opioid peptides. Twenty-four hours after carrageenin, a consistent hyperalgesic effect of naloxone was observable only in rats which had recovered from their carrageenin-induced hyperalgesia. A significant negative correlation between the behavioral effect of naloxone and the degree of hyperalgesia determined for each animal was observed. This suggests that the tonic inhibition exerted by the endogenous opioids was particularly effective in rats which recovered from their initial hyperalgesia. By contrast, these opioid controls could have been weaker in those rats which remained hyperalgesic.

Animals↗

PubMed1991

Effects of guanethidine on sensitization to natural stimuli and self-mutilating behaviour in rats with a peripheral neuropathy.

In the present study we have used a recent rat model for neuropathic pain to investigate the effect of the sympatholytic drug guanethidine on changes in behavioural responses evoked by mechanical, heat and cold stimuli and on self-mutilating behaviour. After a unilateral peripheral mononeuropathy induced by ligatures around the right common sciatic nerve, the left side receiving just a sham wound, lesioned and non-operated control animals were treated with saline or guanethidine (30 mg/kg) for 4 consecutive days commencing 5 days before or 10 days after surgery. Behavioural parameters were followed for 4 weeks after drug treatment. Lesioned rats were found to be sensitized to the otherwise innocuous cold stimulus and showed decreased response thresholds to noxious heat and mechanical stimuli. Some lesioned animals self-mutilated. Treatment with guanethidine diminished heat and cold sensitization considerably, but had less effect on mechanical sensitization and, if administered before surgery, rather increased the severity of self-mutilating behaviour. While these results are in agreement with clinical observations on the prominence of sensitization to evoked stimuli, especially cold, and the effectiveness of guanethidine in sympathetically maintained neuropathic pain, they indicate that the mechanisms involved in sensitization to different stimuli and self mutilating behaviour differ.

Animals↗

PubMed1991

Behavioural evidence for a peripheral component in the enhanced antinociceptive effect of a low dose of systemic morphine in carrageenin-induced hyperalgesic rats.

This study reinvestigated the possible contribution of a peripheral action of systemic morphine in the modulation of the response to noxious pressure on inflamed paws, using a supraspinally integrated test and various low doses of naloxone. Rats received an injection of carrageenin into the right hindpaw which resulted in an ipsilateral inflammatory response and decreased threshold to noxious pressure. Four hours post-carrageenin, the injection of 1 mg/kg i.v. morphine induced a significantly enhanced antinociceptive effect on the inflamed compared to the non-inflamed paws. Intrapantar injection of extremely low doses of naloxone (0.5 and 1 micrograms in a volume of 0.1 ml) significantly reduced this effect (naloxone being more effective when administered at the same time as morphine, compared to 15 min later), while equal doses of naloxone given systemically were inactive. These data confirm that synergism of peripheral and central actions may result in the augmented analgesic potency of morphine in rats subjected to inflammatory conditions. In addition, they provide further evidence for the complexity of opioid actions in inflammatory processes. In particular, the results are in line with the hypothesis that the paradoxical antinociceptive effect of extremely low doses of i.v. naloxone described in several studies is due to a central action.

Analgesia↗

PubMed1991

Single neurone studies of opioid tolerance and dependence at the ventrobasal thalamic level in an experimental model of clinical pain, the arthritic rat.

The aim of this electrophysiological study was to investigate the effects of an acute injection of morphine (1 mg/kg i.v.) or the opioid antagonist naloxone (0.6-2 mg/kg i.v.) on thalamic ventrobasal (VB) neuronal activities recorded in arthritic rats rendered tolerant/dependent by pretreatment with relatively low doses of morphine. Recordings were performed in animals immobilized by i.v. injections of gallamine triethiodide (Flaxedil) and artificially ventilated under a moderate gaseous anesthesia (mixture of one-third O2, two-thirds N2O, 0.5-0.6% halothane). This level of anesthesia, as checked by the electrocorticogram, was stable and appeared sufficiently deep, since no sign of suffering or stress could be detected. The efficacy of morphine on VB neuronal responses induced by mild stimulation of the joints was greatly reduced in morphine-pretreated arthritic rats, compared to naive animals (mean neuronal inhibition of 35 vs 85%, respectively). This indicates that the tolerance phenomena observed in behavioral studies are reflected at the VB level, on neurons involved in pain processes. In addition, naloxone (0.6, 1 and 2 mg/kg i.v.) induced a dramatic increase in the evoked (52, 88 and 93%) and spontaneous (64, 211 and 292%) VB neuronal activities recorded in morphine-pretreated arthritic rats, while these activities were not significantly altered in naive arthritic rats. The time-courses of the modifications induced by naloxone in morphine-pretreated arthritic animals were similar to those of the naloxone-precipitated morphine withdrawal observed in freely moving rats. These findings may represent the neuronal correlate at the VB level of the withdrawal response and/or the hyperalgesia induced in tolerant arthritic rats by high doses of naloxone.

Animals↗

PubMed1991

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↗

PubMed1991

Effects of the analgesic agent tramadol in normal and arthritic rats: comparison with the effects of different opioids, including tolerance and cross-tolerance to morphine.

The effects of the analgesic agent tramadol (0.1-1 mg/kg i.v.) were compared to those of the mixed agonist-antagonist analgesics nalbuphine (1 mg/kg i.v.) and buprenorphine (3 micrograms/kg i.v.) in the vocalization threshold to paw pressure test. Normal and Freund's adjuvant-induced arthritic rats were used. We have shown previously that these animals used as a model of clinical pain exhibit an enhanced sensitivity to morphine (0.1-1 mg/kg i.v.), with a rapid development of tolerance after repetitive low doses, a response not observed in normal rats. In the present study, the antinociceptive effects of tramadol, buprenorphine and nalbuphine were enhanced (by 2- to 5-fold) in arthritic compared to normal rats. In this model, these effects were significantly reduced by a dose of naloxone (0.1 mg/kg i.v.) that completely antagonized the effect of morphine. In this model, the antinociceptive effect of tramadol (1 mg/kg i.v.) was comparable to that of nalbuphine (1 mg/kg i.v.), buprenorphine (3 micrograms/kg i.v.) and morphine (1 mg/kg i.v.). Repeated administration of low doses of tramadol twice daily for 4 days to arthritic rats did not induce tolerance, in contrast to nalbuphine, buprenorphine, and morphine. In addition, no cross-tolerance between tramadol and morphine was observed in these animals.

Animals↗

PubMed1991

Behavioural evidence that systemic morphine may modulate a phasic pain-related behaviour in a rat model of peripheral mononeuropathy.

In a model of peripheral mononeuropathy produced by 4 ligatures around the sciatic nerve, we investigated the effects of various i.v. doses of morphine on the vocalization thresholds elicited by paw pressure and compared the effects obtained with the same doses in normal rats. In neuropathic rats, morphine (0.1 and 0.3 mg/kg) produced a significant analgesic effect on the lesioned hind paw, maximum at 15 min post injection with a recovery at 20-25 min. For doses of 0.6 and 1 mg/kg, a modification of the kinetics was observed, with maximum effect at 20-30 min post injection and a recovery at 50-80 min. An analgesic effect was also observed on the unlesioned side, significantly less potent than that observed on the lesioned paw. The effect of 1 mg/kg morphine was almost totally reversed by a 0.1 mg/kg dose of systemic naloxone. The effects induced by the successive doses of morphine on the lesioned paw appeared higher than in normal rats (maximum vocalization thresholds (% of control) following 1 mg/kg morphine (N = 12) were 193.92 +/- 6.57% versus 154 +/- 3.5% in normal rats N = 3), whereas they were comparable to those obtained from the sham-operated paw. The present data clearly show that morphine induces potent antinociceptive effects in a rat model of neuropathy, which seems to contradict the classical view that neuropathic pain is opioid resistant. Some possible pathophysiological mechanisms are discussed.

Animals↗

PubMed1991

The 'tonic' pain-related behaviour seen in mononeuropathic rats is modulated by morphine and naloxone.

This study investigated the sensitivity to pharmacological manipulations of a rating method, adapted from the formalin test, to measure the tonic component of the pain-related behaviour induced by creating a peripheral mononeuropathy with 4 loose ligatures around the common sciatic nerve. Although the adequacy of opioid substances in alleviating neuropathic pain is highly controversial, the effects of morphine (1 mg/kg i.v.) and naloxone (1 mg/and 3 micrograms/kg i.v.) were tested 1-2 weeks after the nerve ligatures were established, when pain-related behaviours were well developed. Morphine (1 mg/kg i.v.) induced a potent and prolonged decrease in the pain-rating score at week 2 after surgery. Either at week 1 or week 2, naloxone elicited a bidirectional dose-dependent action: a further increase in the pain-rating score with the high dose (1 mg/kg i.v.), and a paradoxical decrease in the score with the low dose of 3 micrograms/kg i.v. These effects are comparable to those already described in several rat models of inflammatory pain and, in the same model of neuropathy, using a phasic nociceptive test, the measure of the vocalization to paw pressure. A few differences in the effects of naloxone on tonic and phasic pain are noted and discussed.

Animals↗