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D Le Bars

Publications and source records attributed to D Le Bars.

At least 163 records · Page 9Linked to original sources
PubMed1983

Diffuse noxious inhibitory controls (DNIC) involve trigeminothalamic and spinothalamic neurones in the rat.

Fifty-eight lumbar dorsal horn and trigeminal nucleus caudalis neurones which could be activated by both innocuous and noxious peripheral stimuli have been recorded in the anaesthetized rat. Using transcutaneous electrical stimulation to produce A and C fibre activity in these neurones from the hindpaw or facial receptive fields the ability of a distant noxious (mechanical or thermal) stimulus applied to the nose, tail, ears and paws to inhibit the neuronal activity was demonstrated. These effects have been termed diffuse noxious inhibitory controls (DNIC). DNIC produced powerful long-lasting inhibitions on all units studied in accordance with our previous results. Approximately 40% of these convergent neurones could be antidromically activated from the contralateral ventrobasal thalamus. Similar neuronal characteristics, effects of DNIC and proportions of projection cells were found in both the dorsal horn and trigeminal complex. However, the spinothalamic tract cells conducted more rapidly than the trigeminothalamic neurones. These results indicate that DNIC can produce comparable effects on the thalamic representation of the efferent activity of these spinal cord and trigeminal neurones. The possible role of DNIC in nociception is discussed.

Animals↗
PubMed1983

Morphine microinjections into periaqueductal grey matter of the rat: effects on dorsal horn neuronal responses to C-fibre activity and diffuse noxious inhibitory controls.

Recording were made for dorsal horn convergent neurones with hindpaw receptive fields. Response to C-fibre activation was conditioned by noxious heat (52 degrees C) applied to the tail, this resulting in profound inhibition (Diffuse Noxious Inhibitory Controls - DNIC). The microinjection of 5 micrograms morphine into the medioventral PAG, including the n. raphé dorsalis, consistently reduced DNIC without affecting the unconditioned C-fibre responses; more lateral injections had no clear effects. Including a further study in which 20 micrograms morphine was microinjected within various PAG sites, C-fibre responses were found to be unaltered (21/51) enhanced (16/51) or reduced (4/51) with no consistent anatomical basis. The results imply that supraspinal morphine can reduce descending inhibitions and this may contribute to the consequent analgesia.

Animals↗
PubMed1982

Pharmacological evidence for the involvement of serotonergic mechanisms in diffuse noxious inhibitory controls (DNIC).

The involvement of serotonergic mechanisms in diffuse noxious inhibitory controls (DNIC) acting on dorsal horn convergent neurones has been studied in the anaesthetized rat. 35 neurones activated by transcutaneous electrical stimulation of their hindpaw receptive fields giving clear large A-fibre and C-fibre responses were recorded. These activities were conditioned by DNIC, evoked by either noxious heat applied to the tail or noxious pinch of the nose. Cinanserin (4 mg/kg i.v.) and metergoline (5 mg/kg i.v.), serotonin (5-HT) receptor blockers, strongly reduced the inhibitory effects of DNIC whilst having no significant effect on the non-conditioned responses. 5-Hydroxytryptophan, a precursor of 5-HT synthesis, significantly potentiated the effect of DNIC. These results indicate an important role for descending serotonergic pathways in DNIC. The functional role of this system is discussed.

5-Hydroxytryptophan↗
PubMed1982

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↗
PubMed1981

The encoding of thermal stimuli by diffuse noxious inhibitory controls (DNIC).

The relationship between stimulus intensity and its efficacy in inducing diffuse noxious inhibitory controls (DNIC) was investigated in anaesthetized rats by using thermal stimulation of the tail for conditioning dorsal horn convergent neuronal responses to C fibres emanating from the hindpaw extremity. The threshold for obtaining inhibition of the neuronal responses ranged between 40 and 44 degrees C and there was a highly significant correlation between noxious temperatures (44-52 degrees C) and the degree of inhibition. These data provide support for the notion of an involvement of inhibitory processes (DNIC) in the signalling of pain by convergent neurones.

Animals↗
PubMed1981

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↗
PubMed1981

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↗
PubMed1981

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↗
PubMed1981

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↗
PubMed1981

[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↗
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

[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

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↗
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↗