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J M Besson

Publications and source records attributed to J M Besson.

At least 19 recordsLinked to original sources
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

Monoarthritis induces complex changes in mu-, delta- and kappa-opioid binding sites in the superficial dorsal horn of the rat spinal cord.

Recently, an experimental model of monoarthritis was described in the rat induced by injection with Freund's adjuvant of the tibio-tarsal joint of one hindlimb. After injection, the clinical and behavioural signs of arthritis are stable from weeks 2 to 6 post-injection. Our purpose was to study the regulation of mu-, delta- and kappa-opioid binding sites in the superficial layers (laminae I-II) of the lumbar and cervical enlargements of the spinal cord 2, 4 and 6 weeks post-injection. Using quantitative receptor autoradiography and highly selective opioid ligands, we found complex changes consisting of a bilateral increase in specific [3H]DAMGO (Tyr*-D-Ala-Gly-NMe-Phe-Gly-ol) and [3H]pCl-DPDPE (Tyr*-D-Pen-Gly-Cl-Phe-D-Pen) binding at 2 weeks post-injection and a bilateral decrease in [3H]U-69593 ((5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-[7-(1-pyrrolidinyl)-1- oxaspiro(4,5)dec-8-yl]) specific binding at 4 weeks post-injection. These changes were restricted to the lumbar level. At 6 weeks post-injection, there was a bilateral increase in [3H]pCl-DPDPE specific binding at both lumbar and cervical levels. Altogether, these results suggest that, after probable local changes in endogenous opioid peptides, the three types of opioid binding sites are differentially involved in the development of the pathological process. These results contrast with the lack of significant modification in mu-, delta- and kappa-opioid binding classically reported at various levels of the spinal cord in polyarthritic rats at 3 weeks post-injection and verified for 2, 4 and 6 weeks post-injection in the present study.

Animals↗
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

Effect of subcutaneous administration of the chemical algogen formalin, on 5-HT metabolism in the nucleus raphe magnus and the medullary dorsal horn: a voltammetric study in freely moving rats.

The effect of subcutaneous administration of the chemical algogen formalin, on serotonin (5-HT) metabolism in the nucleus raphe magnus (NRM) and the medullary dorsal horn (MDH) has been investigated using in vivo 5-hydroxyindole electrochemical (peak '3') detection with treated, multi-carbon fiber electrodes and differential pulse, or normal pulse, voltammetry in freely moving rats. The subcutaneous (s.c.) injection of 50 microliters of 10% formalin in the left forepaw was followed, at the NRM level, by a significant increase in the voltammograms as compared to controls (50 microliters of saline 0.9% s.c. in left forepaw) for about 70 min after the injection, before a return to control values. At the MDH level, the formalin injection induced no significant effect on peak 3, as compared to controls, during the first 70 min. After that, the voltammograms significantly increased and remained above controls for up to 180 min. Thus, the time-courses of NRM and MDH effects appear markedly different. These findings suggest that, depending on the anatomical level (NRM or MDH) and/or the period of observation, one can measure differences in the time-course of the increase in 5-HT metabolism in the NRM-dorsal horn serotonergic system by tonic noxious stimuli, such as the formalin test.

Animals↗
PubMed1992

Fos-like immunoreactivity in the rat superficial dorsal horn induced by formalin injection in the forepaw: effects of dorsal rhizotomies.

As previously described at the lumbar spinal level, we found that 2 h after subcutaneous formalin injection in the distal part of the fore-limb, Fos-like immunoreactivity (FLI) was induced in the ipsilateral cervical enlargement. Not surprisingly, as the injection site corresponds to the distal part of the C6-C8 dorsal root dermatomes, maximal labelling which predominated in the superficial laminae, was observed in the C6-C8 segments and to a lesser extent in C5. Similar experiments were performed on rats which underwent various types of unilateral dorsal rhizotomies (DRh) 7 days before formalin injection. In animals with C4, C5, T1 and T2 DRh sparing C6-C8 the rostrocaudal distribution was similar to the intact one. But, in animals having C4-T2 DRh sparing one single root, C7, the segmental FLI distribution was modified: it was slightly increased in C7, decreased in C6 and significantly decreased in C8. As expected, no FLI was found in animals with C4 to T2 DRh. The spared root model provides information about the segmental distribution in the cervical spinal cord of the input brought by a single root following stimulation of the distal forelimb, i.e., maximal distribution in the entry segment, but also in the two rostral and one caudal segments.

Animals↗
PubMed1992

Time-related decreases in mu and delta opioid receptors in the superficial dorsal horn of the rat spinal cord following a large unilateral dorsal rhizotomy.

The aim of the present study was to measure the time-related modifications of mu and delta opioid binding sites in the superficial layers of the dorsal horn of the rat spinal cord after a C4-T2 unilateral dorsal rhizotomy. Using specific ligands, namely [3H]DAMGO for mu sites and [3H]DTLET for delta sites, and a quantitative autoradiographic analysis, we have observed: (a) a decrease in binding on the ipsilateral side to the lesion as early as the first day postrhizotomy, the maximal loss being attained at 8 days postlesion, (b) after 8 days postlesion, the residual binding remains stable over the period of analysis (90 days), (c) the loss of mu receptors (71-74%) is significantly more pronounced than the loss of delta receptors (57-62%) and (d) affinities of postsynaptic mu and delta receptors are similar to those of the total receptor population in the superficial layers of the dorsal horn. Comparison of these results with the degeneration of primary afferent fibers reported in literature favors the localization of the majority of mu and delta opioid binding sites on fine diameter primary afferent fibers.

Afferent Pathways↗
PubMed1992

Up-regulation of [3H]DAMGO and [3H]DTLET opioid binding sites in laminae I-II of the spinal cord in intact and deafferented morphine-tolerant rats.

Using quantitative autoradiography and selective opioid ligands, we have measured the effects of morphine-induced tolerance on [3H]DAMGO and [3H]DTLET binding sites in the superficial spinal dorsal horn (laminae I-II) of intact and deafferented rats (unilateral C4-T2 dorsal rhizotomy). In intact rats, the treatment induced an up-regulation of 26% and 39% for [3H]DAMGO and [3H]DTLET binding sites, respectively, without modification of receptor affinity. In deafferented rats, the treatment similarly induced an up-regulation of 31% and 29% for [3H]DAMGO and [3H]DTLET binding sites, respectively, on the contralateral side, and of 21% and 25%, respectively, on the ipsilateral side. These data demonstrate that the up-regulation induced by morphine tolerance is of similar magnitude for both presynaptic (on primary afferent fibers) and postsynaptic (on spinal neurons) opioid binding sites in the rat dorsal horn.

Animals↗
PubMed1992

Regulation of opioid binding sites in the superficial dorsal horn of the rat spinal cord following loose ligation of the sciatic nerve: comparison with sciatic nerve section and lumbar dorsal rhizotomy.

The aim of the present study was to quantify time-related modifications in mu and delta opioid binding sites in the superficial layers (laminae I and II) of the L4 lumbar segment in a rat model of mononeuropathy induced by loose ligation of the sciatic nerve. We have shown a 28% (P < 0.01) and 24% (P < 0.01) decrease in ipsi/contralateral side binding ratios for tritiated (Tyr*-D-Ala-Gly-NMe-Phe-Gly-ol) ([3H]DAMGO) and tritiated (Tyr*-D-Thr-Gly-Phe-Leu-Thr) ([3H]DTLET) respectively, at two weeks postlesion which correspond to the delay of maximal hyperalgesia and of maximal alteration of fine diameter primary afferent fibers. In contrast, no change in [3H]U.69593 specific binding could be detected at this postlesion delay. For longer survival delays (four, eight and 15 weeks postlesion), mu and delta binding ratios return towards control values (approximately equal to 1), probably reflecting the occurrence of a long-term neuroplasticity (i.e. a new equilibrium in the metabolism of primary neurons, or collateral sprouting from intact primary afferents) following loose nerve ligation. In addition, a comparison of the results obtained in this model with those measured after sciatic nerve section and lumbar dorsal rhizotomy was performed in order to compare the degree of loss in opioid binding sites in these three types of lesion. The section of the sciatic nerve induced at eight days postlesion an 18% (P < 0.01) and 28% (P < 0.01) decrease in binding ratio for [3H]DAMGO and [3H]DTLET, respectively. At two weeks postlesion the loss was 24% (P < 0.01) for the two ligands, and at longer delays (four and 12 weeks), a progressive recovery in binding ratio was observed. Thus, it appears that both sciatic nerve lesions we have studied result in mu and delta binding modifications which have similar intensity and similar time course from two to 12-15 weeks postlesion. In contrast, the unilateral rhizotomy of nine consecutive dorsal roots (T13-S2), which is known to induce a massive degeneration of fine diameter primary afferent fibers, is followed by a dramatic decrease in binding ratios for [3H]DAMGO (53%, P < 0.001) and [3H]DTLET (45%, P < 0.001) at two weeks postlesion. These data suggest that the more deprived the dorsal horn is of fine diameter primary afferent fibers, the more dramatic is the opioid binding loss in the ipsilateral side as compared to the contralateral side.(ABSTRACT TRUNCATED AT 400 WORDS)

Analgesics↗
PubMed1992

c-fos expression in rat lumbar spinal cord during the development of adjuvant-induced arthritis.

A parallel clinical and behavioral study of adjuvant-induced arthritis in the rat showed four stages in the time-course of the disease: preclinical (first week), acute (weeks 2-4), post-acute (weeks 5-8) and recovery weeks 9-11) [Calvino et al. (1987) Behav. Brain Res. 24, 11-29]. As several studies have reported the expression of the proto-oncogene c-fos in spinal cord neurons following acute noxious peripheral stimuli, the aim of this study was to quantitatively assess Fos-like immunoreactivity in lumbar spinal cord neurons at various times of adjuvant-induced arthritis development, i.e. one, two, three, 11 and 22 weeks post-inoculation. The total number of Fos-like immunoreactive neurons in the lumbar enlargement correlated with the observed development of adjuvant-induced arthritis, i.e. Fos-like immunoreactivity was absent at one week, moderate at two weeks, greatly increased at three weeks, decreased at 11 weeks and returned to control values at 22 weeks. At three weeks, at the peak of Fos-like immunoreactivity distribution and acute stage of hyperalgesia, maximal labeling was observed in L3 and L4 spinal segments. In these segments, the most densely labeled region was the neck (laminae V and VI) of the dorsal horn (55%) and the ventral horn (35%) as compared to the superficial laminae (laminae I and II; 5%) and the nucleus proprius (laminae III and IV; 5%). These data indicate that c-fos expression induced by chronic inflammation is better expressed in deeper laminae than in the superficial ones, and that the number of Fos-positive cells correlates with behavioral studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Voltammetric study of 8-OH-DPAT effect on the raphe-trigeminal 5-HT system.

The effect of i.p. administration of the selective 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) (100 micrograms kg-1) has been investigated by in vivo 5-hydroxyindole electrochemical (peak 3) detection in the nucleus raphe magnus (NRM) and medullary dorsal horn (MDH) of acute anaesthetized and unanaesthetized freely moving rats. 8-OH-DPAT induced a small but significant decrease in peak 3 in the NRM and MDH of anaesthetized rats. In freely moving animals, a similar small effect was observed at both NRM and MDH levels. With reference to similar in vivo studies demonstrating differential responsiveness of ascending serotonergic systems to 8-OH-DPAT, it is concluded that the serotonergic NRM-dorsal horn system is slightly affected by this 5-HT1A agonist.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

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)

Acoustic Stimulation↗
PubMed1991

In vivo electrochemical evidence that the tricyclic antidepressant femoxetine potentiates the morphine-induced increase in 5-HT metabolism in the medullary dorsal horn of freely moving rats.

Acute administration of tricyclic antidepressants (TCAs) is known to potentiate morphine antinociception. At the medullary dorsal horn (MDH) level systemic morphine has been shown to increase serotonin (5-HT) metabolism as measured by in vivo electrochemistry in freely moving rats. Using similar electrochemical detection of 5-hydroxyindole (peak '3') within the MDH, the present study investigated the effect of the specific 5-HT uptake inhibitor femoxetine on peak 3 and the effects of this TCA on changes in 5-HT metabolism induced by morphine. Acutely administered femoxetine (40 mg/kg i.p.) (i) induced a small but significant increase in peak 3 and (ii) strongly potentiated the effect of morphine (10 mg/kg i.p.) on 5-HT metabolism, this potentiation being opiate specific since simultaneous injection of naloxone (1 mg/kg i.p.) abolished the effect of morphine. These findings provide an in vivo neurochemical basis for the potentiation of morphine antinociception by TCAs. They further emphasize the importance of 5-HT bulbospinal descending pathways in morphine antinociception.

Animals↗
PubMed1991

Autoradiographic distribution of mu, delta and kappa opioid binding sites in the superficial dorsal horn, over the rostrocaudal axis of the rat spinal cord.

The purpose of this study was to use [3H]DAMGO, [3H]DTLET and [3H]EKC in the presence of 100 nM DAMGO and 100 nM DTLET, combined with a quantitative autoradiography to analyse the different proportions and the rostrocaudal distribution of mu, delta and kappa opioid binding sites in the superficial layers (laminae I and II) of the cervical (C6-C8), thoracic (T5-T7), lumbar (L3-L5) and sacral (S2-S3) dorsal horn of the rat. The proportions of the three main types of opioid binding sites, assessed by autoradiography in laminae I and II, were found homogeneous at each segmental level considered: 70.4-74.3%, 18.4-20.3% and 7.3-9.5% for mu, delta, kappa sites, respectively. The physiological relevance of these data is discussed.

Animals↗
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

Efferent projections from the external parabrachial area to the forebrain: a Phaseolus vulgaris leucoagglutinin study in the rat.

Small iontophoretic applications of Phaseolus vulgaris leucoagglutinin (PHA-L) were used to study the ascending efferent projections in the rat from the external parabrachial (PBe) area (i.e. external lateral (PBel) and external medial (PBem) subnuclei). It was found that fibers of the caudal two third of PBe project mainly to nucleus centralis of the amygdala (Ce) with a precise pattern: the PBel subnuclei mainly project to the caudomedial subdivision of the Ce and the PBem subnuclei mainly project to the rostrolateral subdivision of the Ce. Another dense and common projection of both subnuclei was found in the ventral pallidal area adjacent to the Ce. This study delineates and extends the terminal area of the spino(trigemino)-ponto-amygdaloid nociceptive pathway demonstrated by our previous studies.

Amygdala↗
PubMed1991

Femoxetine blocks the morphine-induced increase in 5-HT metabolism, as measured by in vivo voltammetry in the nucleus raphe magnus of freely-moving rats.

Tricyclic antidepressants, when administered acutely, are known to potentiate morphine-induced antinociception. Systemic administration of morphine has been shown to increase the metabolism of serotonin (5-HT) at the level of the nucleus raphe magnus, as measured by in vivo electrochemistry, in freely-moving rats. Using a similar electrochemical detection of 5-hydroxyindole (peak "3") in the nucleus raphe magnus, the present study investigated the effect of the specific 5-HT uptake inhibitor, femoxetine, on peak 3 and on changes in the metabolism of 5-HT, induced by morphine. Acutely administered femoxetine (40 mg/kg i.p.) induced a significant decrease in peak 3 and completely abolished the effect of morphine (10 mg/kg i.p.) on the metabolism of 5-HT. These data do not support the contention that potentiation of morphine-induced analgesia, by tricyclic depressants results from an interaction between the tricyclic antidepressants and the morphine-induced increase in metabolism of 5-HT, at the level of the nucleus raphe magnus.

Animals↗