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J M Besson

Publications and source records attributed to J M Besson.

At least 127 records · Page 7Linked to original sources

The depressive effects of morphine on the C fibre response of dorsal horn neurones in the spinal rat pretreated or not by pCPA.

(1) The effects of morphine upon the transmission of nociceptive messages at the spinal level have been investigated in the spinal rat. The responses of dorsal horn cells induced by the activation of C fibres were depressed in all cases in a dose-dependent fashion, this effect being reversed by the opiate antagonist naloxone. An estimation of the ED50 at the cellular level leads to the value of 6.3 mg/kg. The responses to A delta fibres were also depressed dose-dependently whereas the responses to A alpha fibres were unaffected. This is a confirmation in the rat of the differential effects of morphine on responses of convergent units elicited by the stimulation of different fibres, as previously described in the cat. (2) The hypothesis of the participation of serotonergic terminals in these effects has been checked by comparing the preceding results to those obtained in pCPA pretreated animals. Two populations of units were observed in the latter group: two-thirds of cells showed a dose-response curve similar to that of the non-pretreated group whereas the remaining one-third were unaffected either by morphine or naloxone. It is concluded that, at least, two mechanisms are involved in the depressive effects of morphine at the spinal level, serotonergic terminals being implicated in one of these. (3) The lowering of spinal cord serotonin content was associated with a decrease of both the size of the excitatory receptive field (34%) and the activities related to C fibre input (36%) of the recorded dorsal horn cells. This result is discussed with reference to the excitatory or sensitizatory effect of serotonin upon chemoreceptors related to pain.

Animals

The influence of naloxone on the C fiber response of dorsal horn neurons and their inhibitory control by raphe magnus stimulation.

In intact rats anesthetized with chloralose, the effects of naloxone were studied on the responses of spinal cord dorsal horn neurons to C fiber stimulation and upon the inhibition induced on these responses by stimulation of the nucleus raphé magnus (NRM). (1) A mean 44% facilitatory effect on responses to C fibers was observed for 12/19 units. (2) A mean 30% reduction of the inhibitory effects of NRM was found for 14/29 units. (3) However there is no clear relationship between these facilitatory effects and the diminution of the efficiency of NRM stimulation. These results demonstrate a facilitatory effect of naloxone upon the transmission of noxious messages at the spinal level and confirm that opiate endogenous substances are implicated in the inhibitory mechanisms activated by stimulation of NRM.

Animals

Changes in brain and spinal tryptophan and 5-hydroxyindoleacetic acid levels following acute morphine administration in normal and arthritic rats.

The effects of morphine (10 mg/kg/s.c.) on tryptophan (TRP), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels were studied in normal and arthritic rats. (1) In normal rats morphine induced a discrete but significant increase of 5-HIAA levels in the forebrain and the spinal cord. (2) By contrast, in rats suffering from experimentally induced arthritis large modifications were apparent. The basal levels of TRP, 5-HT and 5-HIAA were significantly higher than in normal rats. Morphine induced clear increases of 5-HIAA and TRP in the forebrain, the brain stem and the spinal cord, without any modification of 5-HT. The effects were dose-dependent and suppressed by naloxone (1 mg/kg/i.m.). Statistical analysis clearly revealed that arthritic rats were much more sensitive to morphine. The results support the hypothesis of an activation of a 5-HT descending pathway by morphine which parallels the activation of the ascending pathway previously demonstrated by several authors and confirmed here.

Animals

Role of the nucleus raphe magnus in opiate analgesia as studied by the microinjection technique in the rat.

The analgesic effects of morphine (5 microgram, 0.2 microliter) microinjected into the nucleus raphé magnus (NRM) and the surrounding reticular formation of the rat were tested using vocalization after electric shock to the tail as the test for analgesia. Only sites in the NRM produced powerful analgesic effects, strongest analgesia being equivalent to 3 mg/kg i.v. morphine. The analgesia produced by the microinjection was reversed by systemic naloxone. Pretreatment with systemic cinanserin, a blocker of serotonergic receptors, led to a pronounced diminution of the analgesic effects of the morphine. The effects of microinjections of naloxone (5 microgram 0.2 microliter) were studied for their effect on analgesia produced by systemic morphine. The analgesia following 3 mg/kg i.v. morphine was diminished by the microinjection of naloxone but the naloxone almost completely reversed the analgesic effects of 1.5 mg/kg i.v. morphine. These results further substantiate the role of the NRM in analgesic mechanisms.

Animals

Antinociceptive action following microinjection of methionine-enkephalin in the nucleus raphe magnus of the rat.

The analgesic effect of the microinjection of low doses of methione-enkephalin (20 micrograms in 0.5 microliter) into the caudal brain stem of the unrestrained rat was investigated by means of one vocalisation test. Immediate short duration significant increases in threshold (21%) were seen from sites in the nucleus raphé magnus (NRM). Delayed effects were seen from sites immediately adjacent to this nucleus; sites more lateral produced no significant effect. These results lend further support to the postulated role of NRM in antinociception.

Analgesics

[Effects of morphine on the activity of various dorsal horn neurons of the spinal cord involved in nociception].

In spinal preparation, morphine exerts a specific direct inhibitory action on the activities of dorsal horn neurones induced by noxious stimuli. The effect of morphine is preferential for the responses evoked by A delta and C fibre afferents and its specificity of action has been demonstrated pharmacologically in terms of isomerism, dose dependency and reversal of the inhibitions by opiate antagonists. These results are in good agreement with recent data related to the localization at the spinal level of opiate receptors, and terminal rich in Enkephalin and substance P. Numerous behavioural and pharmacological investigations suggest that morphine is also acting at the level of the brainstem by reinforcing the activity of descending control systems which modulate the transmission of noxious inputs at the spinal level. However this second modality of action remains extremely difficult to demonstrate from an electrophysiological point of view.

Animals

[Role of the Raphe Magnus nucleus in morphine analgesia : studies with intracerebral microinjections in the rat].

Microinjections of low concentration of morphine (5 micrograms) into the nucleus Raphé Magnus of the Rat produce a strong analgesia that can be reversed by systemic naloxone, an opiate antagonist. The administration of naloxone (5 micrograms) into the Raphé Magnus considerably reduces the effects of intravenous morphine. The effects of microinjections of morphine are strongly reduced by Cinanserin, suggesting a role for serotoninergic mechanisms in morphine analgesia.

Analgesia

[Morphine analgesia: neurobiologic data].

Recent Neurobiological (Neurophysiological, Histochemical, Neurochemical and behavioural studies) data have indicated that the analgesic effects of morphine may, at least in part, be explained by two modes of action. A--Morphine has a direct depressive action at a spinal level on the activity of neurones of the grey matter of the dorsal horn which run towards the higher centres of the encephalon. These effects are exerted preferentially on activities induced by the activity of fine non-myelinized fibres (C). These mechanisms are discussed taking into account recent data concerning polypeptides (substance P and encephalins). B--Morphine acts at the level of the brain stem (periaqueductal grey matter, raphian nucleus, etc.) reinforcing the activity of descending bulbo-spinal pathways which block the transmission of painful messages within the cord.

Analgesia

Responses of thoracic dorsal horn interneurons to cutaneous stimulation and to the administration of algogenic substances into the mesenteric artery in the spinal cat.

The effects of the injection of algogenic substances (bradykinin, acetylcholine) into the inferior mesenteric artery were studied at the thoracic level on 47 dorsal horn interneurons responding to cutaneous stimulation. Each unit was characterized by its electrophysiological properties and carefully located within the cord by extracellular injection of pontamine sky blue. Twenty cells, driven only by non-noxious cutaneous stimulation and mainly located in lamina IV, were not affected by the administration of algogenic substances. The activity of 25/27 cells, excited by both non-noxious and noxious cutaneous stimulation and mainly located in lamina V, was strongly modified by nociceptive visceral stimulation, induced by bradykinin and acetylcholine: 8/27 cells were activated, 14/27 were inhibited, 3/27 had a mixed inhibitory-excitatory response. From our study it clearly appears that nociceptive visceral messages only project on dorsal horn cells receiving noxious cutaneous afferents. Thus viscerosomatic convergence seems only to concern nociceptive messages; the existence of this kind of convergence reinforces the hypothesis suggested by several authors to explain referred pain from a neurophysiological point of view.

Acetylcholine

Opiate antagonist, naloxone, strongly reduces analgesia induced by stimulation of a raphe nucleus (centralis inferior).

The analgesic effects obtained in the cat by central inferior raphe nucleus stimulation are greatly reduced by the administration of a specific opiate antagonist, naloxone. In 12 of 16 cats analgesia, tested by pinches applied on the 4 limbs or the tail, was totally abolished. Analgesia tested by considering the increase of the threshold of the jaw opening reflex was reduced to 44% of the initial value. These results emphasize the relation existing between morphine analgesia and analgesia induced by central stimulation. To try to explain the effects of naloxone, one may suppose that central stimulation releases an endogenous morphine-like substance such as enkephalin.

Analgesia

An analysis of response properties of spinal cord dorsal horn neurones to nonnoxious and noxious stimuli in the spinal rat.

Electrophysiological properties of neurones in the spinal cord dorsal horn were studied in decerebrated, immobilized spinal rats. Extracellular recordings were performed at the thoraco-lumbar junction level. Each track was systematically located by extracellular injection of pontamine sky blue. According to their responses to mechanical peripheral stimuli, cells were classified in four classes: Class 1 cells: Cells activated only by nonnoxious stimuli. They were divided into - 1A: hair movement and/or touch and 1B: hair movement and/or touch and pressure or pressure only. Class 2 cells: Cells driven by both nonnoxious and noxious stimuli, divided into - 2A: hair movement and/or touch, pressure, pinch and/or pin-prick, and 2B: pressure, pinch and/or pin-prick. Class 3 cells: Cells only activated by noxious stimuli (pinch and/or pin-prick). Class 4 cells: Cells responding to joint movement or pressure on deep tissues. Peripheral transcutaneous or sural nerve stimulation clearly showed that class 1 cells were activated only by A fiber input while 68% of classes 2 and 3 cells received A and C input. Histological examination indicated that cells driven only by noxious input were located either in the deepest part or in the marginal zone (lamina I) of the dorsal horn. Nevertheless, some lamina I cells were also driven by both nonnoxious and noxious stimuli. In addition, there is a great deal of overlap between class 1 and class 2 cells. This fact was confirmed by considering the wide distribution in the dorsal horn of cells receiving A and C input. However, spinal organization of the different classes of cells consists of a preferential distribution rather than a strict lamination. This study indicates that properties of dorsal horn inter-neurones in the rat have a high degree of similarity with those previously described in other species (cat and monkey).

Animals

Single units activities in ventral posterior and posterior group thalamic nuclei during nociceptive and non nociceptive stimulations in the cat.

The purpose of this study was to define, in hyperventilated and unanesthetized cats, the role of the posterior thalamic nuclei in pain mechanisms. Unit activities of these structures were compared to those of the ventro-posterior nucleus during non-noxious (touch, brushing) and noxious stimulations (pinches and intra-arterial injections of bradykinin into the limbs). 135 cells with somatic inputs and clear peripheral excitatory receptive field were studied. The cells driven by noxious stimulations were located in the posterior group nuclei as anatomically defined by Rinvik. These units, preferentially excited from contralateral receptive fields, were localized in POm, POl, suprageniculate nuclei, the magnocellular division of the medial geniculate body (Mgmc) and the ventral part of the lateral posterior nucleus. At this level two groups of units were found: those driven only by noxious stimulations and those driven by both noxious and non-noxious stimulations. On contrast, cells recorded at the levels of the VPm and VPl were not activated by noxious stimuli. These results emphasize the role of the posterior thalamic nuclei in pain processing.

Animals