Biomedical subjects
Publications and source records attributed to J M Besson.
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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.
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.
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).
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.
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The effects of morphine (2 mg/kg i.v.) upon the transmission of nociceptive messages at the spinal level have investigated in decerebrate cats by studying its effects on the activities of lamina V dorsal horn interneurons. In contrast to previous results obtained on the spinal cat, morphine had little or no effects on lamina V type cells in the decerebrate preparation. The mean values for spontaneous activity and responses to natural noxious stimulation were practically identical before and after morphine administration. Moreover, no significant depressive effect was found on responses induced by supramaximal transcutaneous stimulation. However, for this type of activity a depressive effect was revealed, if only the late component of units which presented bimodal responses were considered. We were unable to demonstrate after morphine administration an increase of the descending inhibitory effects induced on lamina V cells by stimulation of the central inferior nucleus of the raphe. Additional experiments using reversible spinalization (by cooling the cord at the thoracic level) suggest that the lack of effect of morphine on decerebrate animals could be explained by the fact that in this preparation, descending inhibitory influences are strongly exacerbated and thus may mask the depressive effects of this drug. These results indicate that the direct electrophysiological evidence of an increase of the descending control systems after morphine administration must be performed in the intact preparation in order to avoid the effects ot their exacerbation in the decerebrate state.
The effects of steroid anaesthesia (Althesin -CT 1341) on dorsal horn cells (laminae 4 and 5) were studied by extracellular recordings in the spinal cat. I.v. administration of Althesin (0.2 ml/kg) strongly depressed the spontaneous and evoked activities of both types of cells. No differences were found between cells activated by noxious or innocuous stimuli. These results emphasize the fact that the transmission of afferent messages is depressed by various anaesthetics at the level of the first synapses in the CNS. The depressive effects on lamina 5 cells could explain in part the analgesic effects of Althesin.
The effects of morphine upon the transmission of nociceptive messages at the spinal level have been investigated in spinal cats by studying its effects on the activities of lamina V dorsal horn interneurons. Morphine (2 mg/kg i.v.) induced a direct depressive action at the spinal level, since it strongly reduced both spontaneous and evoked activities of lamina V cells. The spontaneous firing rate and the responses elicited by natural nociceptive stimulation were decreased by 50%. The responses of these units evoked by supramaximal electrical stimulation were reduced to 67% of their initial value; in this case, the depressive effect was much more prominent on the late component of the long duration responses. The observed depressive effects are specific since they are immediately reversed by administration of opiate antagonists (nalorphine or naloxone).
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(1) A similar proportion of cells in the VPM (24.7%), MGmc (24%), CM (26.8%) and CL (28.6%) is activated by electrical stimulation of the cat's dental pulp. However the thresholds are very different, cells belonging to the first group of the VPM being often activated by stimulation below 0.1 V. (2) Pain seems to be the unique sensation evoked by pulpal stimulation. A first group of cells somatotopically localized in the VPM displays a primary type of response. These cells can also be activated from an oral or perioral field. This fact is reminiscent of referred pain phenomenon often encountered in the clinic. (3) A second group of cells scattered in the VPM and activated by pulpal stimulation displays a non-primary type of response. (4) Strong pinching of the skin activates some MGmc cells tonically. Response characteristics of the MGmc cells after pulpal stimulation are heterogeneojs. (5) CM cells activated by pulpal stimulation display long latency responses whose properties are similar to those obtained after somatic stimulation. However, the latency of responses are shorter after limb stimulation than after pulpal stimulation.
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The changes in firing rate of mesencephalic reticular units after intra-arterial injection into the limbs of a potent nociceptive agent, bradykinin, were studied in cats (unanesthetized, immobilized with flaxedil and hyperventilated). 30 per cent of the d35 studied cells were affected, 56 per cent were excited, 23 per cent inhibited and 5 per cent had mixed effects. Among the 75 excited cells, the activation of 16 of them seemed to related to the arousa- processes (group A); for 56 cells the increase seemed dire-tly dependent on the nociceptive stimulation itself (group B). The changes of firing rate were repruducible; their latencies and durations were of the same order as the latencies and duration of the nociceptive reactions and painful sensation s, which have been obtained in animals and men after bradykinin injections. The modifications induced by bradykinin administration were suppressed by Ketamin and Thiopental.
In the cat, electrical stimulation of the inferior central nucleus of the raphe induces a powerful analgesia. This stimulation totally suppresses the behavioural reactions elicited by strong pinches applied to the tail or to the four limbs; it strongly modifies the threshold of the jaw opening reflex obtained by tooth pulp stimulation and considerably affects the behavioural reactions elicited by continuing such stimulation. The results can be considered as evidence that the mechanism of analgesia from the inferior raphe nucleus is similar to that already described in the dorsal raphe nucleus. The analgesia obtained by stimulation of raphe nuclei seems to be sustained by serotoninergic mechanisms and relationships between these are discussed. In preliminary experiments, analgesia induced by CI stimulation has been suppressed by administration of naloxone, a specific opiate antagonist.
1. In order to study descending influences of the brain stem upon the transmission of nociceptive messages at the spinal level, the activities of lumbar lamina V dorsal horn cells, induced by intra-arterial injection of brandykinin into the limbs, were recorded in unanaesthetized cats in both decerebrate and temporary spinal states (reversible cold block applied at the thoracic level). 2. In the decerebrate state, the intra-arterial injection of bradykinin had little or no effect. 3. During the reversible spinalization, the effects of bradykinin were revealed or considerably enhanced. As described in a previous study, in the C1-transected cat, three types of effects were encountered: excitatory, inhibiitory and mixed (inhibitory-excitatory). 4. These modifications observed after spinalization were generally associated with a large increase of the spontaneous firing rate. 5. These results emphasize, in the decerebrate cat, the importance of descending inhibitory controls exerted by the brain stem upon the transmission of nonciceptive messages at the spinal cord level.