Search PubMed⌕ Search

Biomedical subjects

J M Besson

Publications and source records attributed to J M Besson.

At least 181 records · Page 10Linked to original sources
PubMed1981

[Involvement of serotoninergic systems in analgesia induced by electrical stimulation of brain stem areas (author's transl)].

Numerous studies in the rat have shown that powerful analgesia can be induced by electrical stimulation of the periaqueductal grey matter (PGM). From an extensive mapping (300 sites of stimulation) performed on unrestrained cats, we have demonstrated that the points from which analgesia can be obtained are essentially located in the raphe nuclei: dorsal raphe nucleus (DRN) located in the ventral part of the PGM, superior part of the nucleus central superior (CS) and nucleus central inferior (mainly the raphe magnus: RM). The most powerful effects were induced by stimulation sites located in the RM. At this level, similar findings were also obtained in the rat. Accumulating evidence suggests that electrical analgesia (EA) results, partly, from the activation of bulbospinal systems which block the transmission of noxious messages at the spinal level: (a) Spinal cord nociceptive reflexes and jaw-opening reflex induced by tooth pulp stimulation are suppressed by EA. (b) Responses of dorsal horn neurons to noxious stimuli are drastically reduced by PGM and RM stimulations; similar findings have been reported for trigeminal neurons in the nucleus caudalis. (c) Neurons at the origin of the spinothalamic tract in the monkey or at the origin of the spinoreticular tract in the rat are strongly inhibited by RM stimulation. These electrophysiological results are in agreement with anatomical data showing that RM has dense projection at the level of the dorsal horn. All these results clearly demonstrate that the raphe nuclei, rich in serotoninergic cell bodies, seem to play a basic role in the mechanism of electrical analgesia. The involvement of serotonin is strongly suggested by numerous behavioral, electrophysiological, anatomical and neurochemical investigations. In addition, PGM and RM are strongly implicated in morphine analgesia which has several common characteristics with EA. The most striking evidence results from the observation that EA is decreased or suppressed after administration of an opiate antagonist (Naloxone). This observation suggests that electrical stimulation releases morphine-like endogenous substances.

5-Hydroxytryptophan↗
PubMed1980

Diffuse noxious inhibitory controls (DNIC). Effects on trigeminal nucleus caudalis neurones in the rat.

We have extended our previous description at the dorsal horn level of Diffuse Noxious Inhibitory Controls (DNIC) to the trigeminal nucleus caudalis of the intact anaesthetized rat. These controls produce powerful long-lasting inhibitions of all activities of convergent neurones and can be elicited by noxious stimuli applied to widespread areas of the body unrelated to the receptive fields of the neurones under study. In nucleus caudalis, 39/40 convergent neurones were found to be under DNIC produced from the tail, paws, viscerae, nose and ears. DNIC was only elicited by noxious stimuli which included pinch, noxious heat and intraperitoneal bradykinin. DNIC strongly inhibited both the A fibre and C fibre related activities of trigeminal convergent neurones whether evoked electrically or naturally with the degree of inhibition ranging between 55 and 100% in the most cases. Of 43 non-convergent neurones, noxious only, innocuous, proprioceptive and cold responsive, 42 were unaffected by DNIC. The results demonstrate that both the neuronal responses and DNIC at the trigeminal nucleus caudalis level in the rat are similar to those reported for the dorsal horn.

Animals↗
PubMed1980

Effect of acute administration of morphine on newly synthesized 5-hydroxytryptamine in spinal cord of the rat.

The effect of morphine (10 mg/kg, s.c.) on the rate of [3H]5-HT synthesis in brain and spinal cord following intravenous injection of [2H]tryptophan was studied in the rat. (1) In the spinal cord morphine induced an increase in [3H]TRP uptake which was significant 30 and 60 min after the injection, and a clear enhancement of the formation of [3H]5-HT which was significant 15 min after the injection and which peaked at 30 min. In the forebrain, the increase in [3H]TRP accumulation was significant as early as 15 min after morphine. At this time, the rate of 5-HT synthesis was not modified, but it was significantly increased 30 and 60 min after the injection. (2) Increases in [3H]5-HT synthesis rate were suppressed by naloxone (1 mg/kg, i.m.). However this narcotic antagonist did not significantly reduce the increased accumulation of [3H]TRP in brain and spinal cord due to morphine treatment. These results demonstrate that morphine induces a fast and marked increase in 5-HT synthesis, and suggest that this increase is only partly related to an increase in the availability of tryptophan to the central nervous system. These results are in good agreement with recent investigations showing the involvement of the raphe-spinal system in morphine analgesia.

Animals↗
PubMed1980

[Depression by morphine of various descending inhibitory controls modulating the transmission of nociceptive information at the spinal level in the rat].

Recording from convergent neurones--i. e. those responding to both non-noxious and noxious cutaneous stimuli--in the dorsal horn of the intact anaesthetized Rat, two distinct effects are seen after application of noxious stimuli: there is an activation of units of the segmental pool, along with a very powerful inhibition of the remaining neuronal population (diffuse noxious inhibitory controls, DNIC). Morphine at doses inadequate to directly depress the activity of these units specifically blocks the inhibition. Since DNIC is dependent upon supraspinal mechanisms, these observations show that morphine is capable of depressing certain descending inhibitory controls, at least when these are induced by noxious peripheral stimuli.

Animals↗
PubMed1980

Encoding of noxious heat messages in neurons of the ventrobasal thalamic complex of the rat.

Ventrobasal thalamic neurons responsive to noxious mechanical stimuli were tested with noxious heat stimuli graded in temperature, surface-area and duration. Experiments were performed by plunging the tail of intact, lightly anesthetized rats into a temperature-controlled water bath. Seventeen of 24 neurons encoded stimulus temperature by frequency of discharge although the responses of 6 of these 17 reached a plateau at the highest temperatures. Alternatively, the cell population might code stimulus temperature by a recruiting mechanism since response thresholds were distributed between 40 and 50 degrees C. Some units also increased their discharge in parallel with an increase in stimulus area and/or duration. Analyses of discharge patterns were performed. A decrease of discharge frequency during stimulation was not observed before several tens of seconds had elapsed. Thus, the average response of the cell population to 15, 30 and 60 sec stimuli showed no clear 'adaptation'. In our conditions, i.e. with most of the stimulations limited to a duration of 15 sec each, sensitization to heat was observed after 55 and 60 degrees C, but not after 50 degrees C. These data indicate that noxious heat stimulus parameters are coded at the thalamic level in the rat by both an increase in discharge and a progressive recruitment of units.

Animals↗
PubMed1980

Electrical stimulation of the nucleus raphe magnus in the rat. Effects on 5-HT metabolism in the spinal cord.

The direct electrical stimulation (with biphasic pulses of 1 msec, 10 pulses/sec, 200 microA, for 30 min) of the nucleus raphe magnus in chloral hydrate anaesthesized rats produced a significant acceleration (+50%) of 5-HT synthesis in the spinal cord as revealed by the increased rate of 5-HTP accumulation occurring at this level after the blockade of central 5-HTP decarboxylase with benserazid. In contrast, no change was detected in 5-HT metabolism in the forebrain of stimulated rats. The acceleration of 5-HT synthesis was likely not due to an increased availability of tryptophan for the rate-limiting enzyme, tryptophan hydroxylase, since the concentration of this amino acid was changed neither in the spinal cord, nor in the forebrain of stimulated rats. The measurement of tryptophan hydroxylase activity in soluble extracts from the spinal cord of control and stimulated rats revealed that the acceleration in 5-HT synthesis produced by the electrical stimulation of the nucleus raphe magnus was not associated with a persisting activation of this enzyme. Although one cannot completely exclude that a short-lasting activation of tryptophan hydroxylase, no longer detectable in soluble extracts, has occurred in the spinal cord of stimulated rats, the present findings rather suggest that the rate of 5-HT synthesis can be controlled by factors other than only the concentration of tryptophan and the intrinsic activity of tryptophan hydroxylase in serotoninergic neurons. The demonstration of an acceleration of 5-HT synthesis in bulbospinal serotoninergic neurons under stimulating conditions close to those producing analgesia in rats further supports the role of these neuronal systems in the physiological mechanisms of pain control.

5-Hydroxytryptophan↗
PubMed1980

Microinjection of morphine within nucleus raphe magnus and dorsal horn neurone activities related to nociception in the rat.

The hypothesis of an increase by morphine of descending inhibitory controls acting upon the transmission of painful messages at the spinal level has been directly investigated in intact anaesthetized rats. The analgesic efficacy of morphine microinjections (5 micrograms in 0.2 microliter saline) applied within the nucleus raphe magnus (NRM) was examined using the threshold for vocalization after electric shock to the tail as a test: a mean threshold increase of 57% was observed. A few days later, the effects of similar microinjections upon dorsal horn cell activities were studied in acute experiments in the same animals. The response of dorsal horn convergent units induced by the activation of large myelinated (Aa) afferent fibres were unaffected by the microinjection of morphine within the NRM. In the case of the responses of convergent units induced by the activation of unmyelinated (C) afferent fibres, two different results were obtained after microinjection of morphine within the NRM: 8/14 units were not affected and 6/14 were clearly excited. A transient reversal of the excitatory effects was observed after the systemic administration of the opiate antagonist naloxone. The responses of marginal layer cells (lamina 1) were unaffected by the microinjection of morphine within the NRM. These unexpected results are discussed in view of the fact that they conflict with current concepts regarding morphine analgesia.

Animals↗
PubMed1980

[Role of serotonin in the diffuse inhibitory controls induced by nociceptive stimulation].

In the anaesthetized Rat, the entire population of dorsal horn convergent neurones is differentially affected by a noxious stimulus: while exciting the segmental pool, it strongly inhibits the remaining population. The inhibitory effects, which involve supraspinal mechanisms, are reduced to a great extent in parachlorophenylalanine pretreated animals. The role of raphé-spinal serotonergic pathways in nociception is discussed.

Animals↗
PubMed1980

Location and properties of dorsal horn neurons at origin of spinoreticular tract in lumbar enlargement of the rat.

1. Spinoreticular tract neurons at the rat lumbar cord level were identified by antidromic activation following stimulation at mainly pontine and mesencephalic levels. These units, which were found in the dorsal half of the cord, could be separated into two groups according to their spinal location, electrophysiological properties, and their central projections. 2. Units in the dorsolateral funiculus nucleus projected mainly to the cuneiformis area and adjacent structures with frequent bilateral projections. They had the slowest conduction velocities, sometimes in the unmyelinated range. Generally, they were driven only by stimulation of subcutaneous and/or deep structures. 3. Neurons located in the dorsal horn mainly projected contralaterally to pontine and mesencephalic levels. their conduction velocities and the electrophysiological properties were identical to those observed for the rat spinothalamic tract (22). Almost all (86%) had clear cutaneous sensitivity and generally large receptive fields: 40% responded to nonnoxious and noxious mechanical cutaneous stimuli and frequently to noxious radiant heat, 26% were exclusively excited by light tactile stimuli, and 20% required noxious cutaneous mechanical stimulation for activation. There was a good correlation between responses to natural and transcutaneous electrical stimulation: units driven by noxious mechanical stimuli received A-delta- and/or C-fiber inputs. The remaining units (14%) had more complex receptive fields associated with both excitatory and inhibitory inputs originating from a single peripheral area. 4. The functional heterogeneity of the rat spinoreticular tract is reminiscent of that demonstrated for the rat and monkey spinothalamic tracts. Similarly, the rat spinoreticular neurons are under the influence of descending inhibitory controls originating from the nucleus raphe magnus and bulbar reticular formation. 5. Responses of the rat spinoreticular tract neurons are consistent with the involvement of this pathway in the transmission of messages of both innocuous and noxious origins.

Afferent Pathways↗
PubMed1980

Nucleus raphe magnus modulation of response of rat dorsal horn neurons to unmyelinated fiber inputs: partial involvement of serotonergic pathways.

1. In the rat under N2O-halothane anesthesia, stimulation of the nucleus raphe magnus (NRM) with stimulus parameters similar to those used to obtain analgesia in freely moving animals strongly inhibits the responses of dorsal horn convergent neurons due to A-delta- and C-afferents. 2. Responses to noxious radiant heat were also depressed, and pronounced post-effects were frequently observed. 3. Comparison between coupled sites of stimulation in NRM and in adjacent bulbar reticular formation (BRF) on responses to C-fibers revealed the preeminent effects of NRM; these were systematically encountered (93% of neurons), much more pronounced, and of longer duration. 4. The latency of these inhibitory effects (around 20 ms) suggests the participation of myelinated axons in such descending action and, consequently, we question the involvement of unmyelinated serotonergic fibers. 5. However, descending inhibitory influences from NRM on responses to C-fibers are reduced after 5-hydroxytryptamine (5-HT) depletion by p-chlorophenylalinine (pCPA), thus demonstrating the implication of both serotonergic and nonserotonergic pathways. 6. In addition, after pCPA pretreatment, long-lasting and sustained excitatory effects from NRM were observed in 35% of convergent neurons; their possible origin is discussed.

Animals↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗
PubMed1979

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↗