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J M Besson

Publications and source records attributed to J M Besson.

At least 163 records · Page 9Linked to original sources

Neurons at the origin of the medial component of the bulbopontine spinoreticular tract in the rat: an anatomical study using horseradish peroxidase retrograde transport.

An anatomical technique based on the retrograde transport of horseradish peroxidase (HRP) was used to investigate the projections of spinal cord neurons to the reticular formations in the rat. Both large and restricted injections were staggered all along the bulbar and pontine levels, involving the nucleus gigantocellularis, the nuclei reticularis pontis, pars oralis and caudalis and in some cases the nucleus raphé magnus. Labeled cells were constantly encountered in the reticular part of the neck of the dorsal horn throughout the whole length of the cord, mainly contralateral to the central core of the injection site. This area was taken as the equivalent of lamina V in the cat. Other labeled cells were observed in the medial parts of the intermediate and ventral horns, in areas considered similar to laminae VII and VIII in the cat. The two most rostral cervical segments were characterized by an additional bilateral projection originating from the dorsolateral part of ventral horns. Thus, this study is a clear confirmation that the bulbopontine reticular formations constitute a target for various somatosensory inputs originating in spinal cord. It demonstrates that the medial spinoreticular tract (mSRT) differs from the other main ascending tracts by the absence of projections from (1) superficial layers and nucleus of the dorsolateral funiculus contrary to the spinomesencephalic tract; (2) ventromedial zone of the lumbar dorsal horn unlike the spinothalamic tract; (3) the neck of the dorsal horn in its medial portion contrary to the spinoreticular component reaching the lateral reticular nucleus; and (4) central cervical nucleus and Clarke's columns, unlike the spinocerebellar tracts. The difficulty in demonstrating retrograde labeling from discrete injections could result from the fact that mSRT neurons have sparsely ramified collaterals on their terminal zones.

Afferent Pathways↗

Increase of serotonin metabolism within the dorsal horn of the spinal cord during nucleus raphe magnus stimulation, as revealed by in vivo electrochemical detection.

Carbon fiber microelectrodes were used with the differential pulse voltammetry method for in vivo determination of indolamines within the extracellular space of the dorsal horn of the spinal cord or chloral hydrate-anesthetized rats. Under these conditions a peak of oxidation current which is characteristic of 5-hydroxyindoles is recorded at 280-300 mV. Stimulation of the nucleus raphé magnus (NRM) with stimulation parameters comparable to those used to elicit analgesia in freely moving animals produced marked alterations in the voltammograms: (1) stimulation of the NRM for 10 min induced an immediate and sustained increase in the peak amplitude; (2) post-effects of variable duration were observed; (3) the increase in the 5-hydroxyindolaminergic signal was significantly reduced during a second series of NRM stimulations indicating some degree of tolerance to central stimulation. The accuracy of these observations is strengthened by the fact that the basal 5 hydroxyindolaminergic signal is strongly depressed after pretreatment of the animal with p-chlorophenylalanine; in addition, under these conditions, NRM stimulation is totally inefficient. We suggest that these results reflect the in vivo modification of 5-HT metabolism. This represents the first evidence for an in vivo release of 5-HT during stimulation of brain stem areas which induces powerful analgesia in freely moving animals.

Animals↗

Increased levels of Met-enkephalin-like material in the CSF of anaesthetized cats after tooth pulp stimulation.

Tooth pulp stimulation in halothane-anaesthetized cats induced a long lasting (greater than or equal to 3 h) increase in the levels of Met-enkephalin-like material (MELM) in the cisternal CSF. Chromatographic analyses (gel filtration, HPLC) revealed that most of the immunoreactivity was attributable to high molecular weight (mol. wt. greater than or equal to 4000) compounds; in non-stimulated cats, Met-enkephalin (largely in the form of the sulfoxide derivative) only accounted for about 10% of total MELM. In contrast, following tooth pulp stimulation, a large increase in Met-enkephalin (plus Met-Ox5-enkephalin) levels was noted so that the pentapeptide thus represented more than 50% of total MELM. No evidence was obtained for the presence of Met-enkephalin-Arg6-Phe7 in the cisternal CSF of halothane-anaesthetized cats. These data strongly suggest that the activity of enkephalinergic neurons was increased following nociceptive stimulation. This indirectly supports the possible physiological role of enkephalinergic systems in modulating nociceptive inputs.

Animals↗

The origin of the spinomesencephalic tract in the rat: an anatomical study using the retrograde transport of horseradish peroxidase.

An anatomical technique based on the retrograde transport of horseradish peroxidase (HRP) was used to investigate the projections of spinal cord neurons to the mesencephalic tegmentum in the rat. Restricted unilateral injections were confined to central grey, cuneiformis areas, and superior colliculus. Injections into all these loci produced labeling in similar spinal areas. Only quantitative differences were noted. In the spinal grey matter, numerous labeled cells were regularly encountered in the marginal zone, the lateral part of the neck of the dorsal horn, and the dorsal grey commissure. Projections from the marginal zone and neck of the dorsal horn were predominantly contralateral. In the white matter, a pronounced bilateral labeling was observed in the nucleus of the dorsolateral funiculus, thus confirming our previous electrophysiological findings (Menétrey et al., '80). This distribution of labeled cells was commonly observed throughout the whole length of the cord. Additional sites of projecting cells have also been identified at the most rostral levels (obex, C1, C2). They mostly derived from spinal extensions of the dorsal column nuclei and lateral cervical nucleus contralaterally; from the lateral ventral horns bilaterally and from the nucleus commissuralis ipsilaterally. This study is thus a clear confirmation that the mesencephalic tegmentum constitutes a target for various somatosensory inputs originating from spinal cord, dorsal column nuclei, and lateral cervical nucleus. Moreover, from these results together with those obtained for the spinothalamic tract in the rat, it appears that marginal and dorsolateral funiculus neurons preferentially project to the mesencephalic tegmentum. The importance of marginal zone projections underlines the involvement of the spinomesencephalic tract in pain mechanisms.

Afferent Pathways↗

Possible involvement of the amygdaloid complex in morphine analgesia as studied by electrolytic lesions in rats.

The analgesic effects of morphine (5 mg/kg i.p.) were studied in biamygalectomized rats. (1) Using the tail-flick test neither withdrawal latencies nor morphine time-course and efficacy were affected by the lesions. (2) The threshold for vocalization to electrical stimulation of the tail was greatly increased in lesioned rats; however, statistical analysis revealed no significant change in the analgesic efficacy of morphine.

Amygdala↗

Behavioral model for diffuse noxious inhibitory controls (DNIC): potentiation by 5-hydroxytryptophan.

The effects of the serotonin precursor 5-HTP, were determined in a behavioral DNIC paradigm (increase in vocalization threshold after intraperitoneal injection of the algogenic agent, phenylbenzoquinone). This counter-irritation phenomenon was strongly potentiated by 5-HTP, such potentiation being blocked by the 5-HT receptor blocker, cinanserin. These results are in keeping with those of our recent single unit work in dorsal horn convergent neurons.

5-Hydroxytryptophan↗

The relationship between morphine analgesia and the activity of bulbo-spinal serotonergic system as studied by tolerance phenomenon.

The effect of various doses of acute morphine on both analgesia and 5-hydroxytryptamine (5-HT) synthesis in the brain and the spinal cord has been studied in rats rendered tolerant by chronic administration of the analgesic. In morphine-tolerant rats, the incorporation of tritiated-L-tryptophan (TRP) in the brain and the spinal cord was higher than in non-tolerant rats, but there was no significant difference in the synthesis rate of the newly formed 5-HT between the two groups. An acute dose of morphine (10 mg/kg) which induced a powerful analgesia and a large increase in 5-HT synthesis in non-tolerant rats, did not produce analgesia nor changes in 5-HT synthesis in tolerant rats. Higher acute doses of morphine which restored analgesia in tolerant rats, induced a discrete increase in [3H]TRP incorporation and a marked increase in 5-HT synthesis in the spinal cord of these animals. The same doses significantly increased [3H]TRP incorporation in the forebrain but did not modify 5-HT synthesis. These results show that tolerance to morphine is associated with a decrease in the effects of the drug on 5-HT synthesis in the spinal cord and the brain and tend further support to the hypothesis that an enhancement of 5-HT synthesis in the spinal cord, induced independently of modifications of the availability of TRP, is associated with the analgesic effect of morphine.

Animals↗

Diffuse noxious inhibitory controls (DNIC) in the rat with or without pCPA pretreatment.

Diffuse Noxious Inhibitory Controls (DNIC) were investigated in anaesthetized intact rats, with or without p-chlorophenylalanine (pCPA) pretreatment. Dorsal horn convergent neurones responding to both noxious and non-noxious stimuli applied to their excitatory receptive field located on the distal part of the hindlimb, were recorded in the lumbar spinal cord. These cells received A alpha and C fibre inputs as shown by electrical stimulation of their receptive field. In control animals, the evoked responses to C fibre inputs could be strongly inhibited by various noxious stimuli applied to widespread areas of the body: the inhibitory effects induced by intraperitoneal administration of bradykinin, pinch applied to the tail or muzzle and noxious heat applied to the tail were of 77%, 87%, 83% and 61% respectively. Long-lasting post-effects were seen in most cases after cessation of the application of the conditioning stimulus. Pretreatment with pCPA (300 mg/kg, i.p., 3 days) resulted in a strong reduction of DNIC. The inhibitory effects induced by intraperitoneal administration of bradykinin, pinch applied to the tail or muzzle and noxious heat applied to the tail were reduced by 47%, 63%, 87% and 63%, respectively. The post-effects were also reduced both in terms of magnitude and duration. These results strongly suggest that serotonergic pathways partially involved in DNIC. They are discussed with reference to the descending control systems, originating from the caudal raphé, which modulate the transmission and/or the integration of nociceptive messages at the spinal level. The possible involvement of DNIC and 5-HT mechanisms to the hypo-algesic phenomena induced by hyper-stimulation is also suggested.

Animals↗

Endogenous opiates and nociception: a possible functional role in both pain inhibition and detection as revealed by intrathecal naloxone.

Naloxone, the opiate antagonist, was injected into the intrathecal space of rats in doses of 15, 30 and 60 micrograms to gauge its effect on the nociceptive threshold as measured by the vocalization test. Whereas 60 micrograms of naloxone produced hyperalgesia, injections of 15 micrograms lead to hypoalgesia. These opposite effects of naloxone depending on the dose used do not support the idea that endogenous opiates have unequivocal effects on pain transmission, and an alternative hypothesis of their role is discussed.

Animals↗

The effect of systemic morphine upon diffuse noxious inhibitory controls (DNIC) in the rat: evidence for a lifting of certain descending inhibitory controls of dorsal horn convergent neurones.

The effects of exogenous opiates upon diffuse noxious inhibitory controls (DNIC) was investigated in intact anaesthetized rats. 58 convergent neurones, responding to both noxious and innocuous stimuli applied to their cutaneous receptive fields, were recorded at the lumbar level. These cells received A- and C-peripheral fibre inputs as shown by electrical stimulation of their receptive fields and were mainly located in the medial part of the dorsal horn. The immersion of the distal two-thirds of the tail in hot water (52 degrees C) induced strong inhibition of the responses to both A-(23%) and C-(69%) fibres. Post-effects of long duration were commonly observed after cessation of the conditioning stimulus. While systemic injection of morphine at a low dose-range (0.1-1 mg/kg) did not significantly affect the unconditioned responses, the DNIC-mediated inhibitions were profoundly altered. (a) DNIC of responses to C fibres were dose-dependently (P less than 0.01) lifted by morphine: (b) the post-effects observed after cessation of conditioning stimuli were dose-dependently (P less than 0.01) diminished; (c) DNIC of responses to A-fibre were similarly altered but this effect was less significant (P less than 0.05); (d) DNIC of responses to sustained moderate pressure were greatly diminished by morphine (P less than 0.01); and (e) these effects were specific since they were antagonized by the opiate antagonist, naloxone. In addition, they were shown to be stereospecific since while the dextrogyre stereoisomer, dextrorphan, was ineffective the levogyre derivative, levorphanol, induced a significant lifting of DNIC. It is concluded that morphine decreases the supraspinal inhibitory controls of dorsal horn convergent neurones, at least when these controls are triggered by noxious stimuli. Assuming that a basic somatosensory background activity (noise) is transmitted to higher centres by dorsal horn convergent neurones, and that the pain-signalling message is the contrast between the activity of the segmental pool of neurones induced by the noxious stimulus and the DNIC-mediated silence of the remaining neuronal population, it is proposed that, by a reduction in DNIC, low-dose morphine could restore the initial level of background activity, the final result being analgesia.

Animals↗

Morphine analgesia and newly synthesized 5-hydroxytryptamine in the dorsal and the ventral halves of the spinal cord of the rat.

In the rat, morphine (5 mg/kg, s.c.) induced an increase in 5-hydroxytryptamine (5-HT) synthesis in the spinal cord. These effects appeared with a shorter latency and are much more marked in the dorsal half than in the ventral half. Although the increase in the dorsal half was slightly delayed by comparison with the onset of the analgesic effect the maxima for both phenomena were simultaneous. The role of the bulbo-spinal serotonergic system in morphine analgesia is discussed.

Animals↗

[Motor or aversive effects associated with analgesic effects induced by electric stimulation of the periaqueductal gray matter in rats].

The analgesia induced in the Rat by a stimulation applied to the periaqueductal gray matter (PAG) was reevaluated. With the exception of a few stimulation sites located in the ventral PAG, the stimulation-induced analgesia was generally accompanied by strong aversive effects (dorsal and dorsolateral PAG) or motor effects (ventral PAG). These results raise the problem of a possible involvement of "stress-produced analgesia" and motor disturbances in the production of analgesia by PAG stimulation.

Analgesia↗

Effect of naloxone upon diffuse noxious inhibitory controls (DNIC) in the rat.

Twenty-eight convergent neurones, responding to both noxious and innocuous stimuli applied to their cutaneous receptive fields were recorded at the lumbar level in anaesthetized intact rats. These cells received Aa and C fibre inputs as shown by electrical stimulation of their receptive fields, and were located in the medial part of the dorsal horn. (a) For 15 units, Diffuse Noxious Inhibitory Controls (DNCI)67,68 were investigated by applying noxious thermal stimuli (52 degrees C) to the distal two-thirds of the tail. This conditioning stimulus induced strong inhibition of the responses to both Aa (28%) and C (71%) fibres. Post-effects of long duration were commonly observed after cessation of the conditioning stimulus. The systemic injection of naloxone (0.3 mg/kg, i.v.) resulted in a partial reduction in these inhibitory effects with a decrease of about 50% for both Aa and C fibre response 10 min after naloxone administration. This was followed by a progressive recovery lasting 30 min. (b) 28 convergent units, including the 15 reported above, were recorded to investigate the effect of naloxone upon the unconditioned response. Responses to Aa fibre were unaffected, whereas the responses to C fibre were slightly (17%) but significantly increased by naloxone.

Afferent Pathways↗

[Are bulbo-spinal serotonergic systems involved in the detection of nociceptive messages? (author's transl)].

Intensely noxious peripheral stimuli of the anaesthetized rat produce two changes in the activity of convergent dorsal horn units: the segmental neuronal pool is activated, while all other convergent neurones are inhibited. These Diffuse Noxious Inhibitory Controls (DNIC) are highly potent (60-80% inhibition) and suppress all convergent neuronal activity, whether spontaneous or evoked by noxious or nonnoxious stimuli. On the other hand, they have no effect on other dorsal horn cell types, including noxious-only and proprioceptive units. The "DNIC" circuits include at least one supraspinal relay since DNIC is not seen in spinal animals. Furthermore, they are greatly reduced by lesions of the Nucleus Raphé Magnus (NRM). It has been shown that this nucleus massively projects onto the spinal cord, in particular onto the dorsal horn, and that stimulation of the NRM results in convergent unit inhibition of the same degree of magnitude as with DNIC. The role of serotonergic mechanisms in DNIC can be demonstrated pharmacologically: pCPA pre-treatment (3 daily I.P. injections, 300 mg/kg) or cinanserin (4 mg/kg I.V.) both result in a potent decrease (50-80%). We have proposed that the nociceptive message from the convergent units could result in a contrast between activity of the activated segmental pool and silence of the remaining convergent units. If this hypothesis can be verified, then some raphé nuclei and brain stem serotonergic pathways may function as filters in the detection of nociceptive messages, allowing extraction of information from somatic background activity including the firing from peripheral mechanoreceptors. While superficially paradoxical in fact our hypothesis fits well with the observation of profound analgesia following NRM stimulation: indeed, this hypothetical contrast would be completely eliminated by NRM stimulation since both neuronal pools would then be inhibited.

Animals↗