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Biomedical subjects

D Le Bars

Publications and source records attributed to D Le Bars.

At least 73 records · Page 4Linked to original sources
PubMed1995

Distribution of spinal cord projections from the medullary subnucleus reticularis dorsalis and the adjacent cuneate nucleus: a Phaseolus vulgaris-leucoagglutinin study in the rat.

The distribution and organization of descending spinal projections from the dorsal part of the caudal medulla were studied in the rat following injections of Phaseolus vulgaris-leucoagglutinin into small areas of the subnucleus reticularis dorsalis (SRD) and the adjacent cuneate nucleus (Cu). The caudal aspect of the Cu projected only to the dorsal horn of the ipsilateral cervical cord via the dorsal funiculus. These projections were mainly to laminae I, IV, and V. More ventrally located reticular structures projected to the full length of the cord. Fibers originating from the SRD travelled through the ipsilateral dorsolateral funiculus and terminated within the deep dorsal horn and upper layers of the ventral horn, mainly in laminae V-VII. Fibers originating from subnucleus reticularis ventralis (SRV) travelled ipsilaterally through the lateral and ventrolateral funiculi and bilaterally through the ventromedial funiculus. These fibers terminated within the ventral horn. The density of labeling within the gray matter varied at different levels of the cord was as follows: cervical > sacral > thoracic > lumbar. The reciprocal connections between the caudal medulla and the spinal cord suggest that the former is an important link in feedback loops that regulate spinal outflow.

Animals↗
PubMed1995

Audible and ultrasonic vocalization elicited by single electrical nociceptive stimuli to the tail in the rat.

We describe audible and ultrasonic vocalization elicited in rats by a short electrical pulse applied to the tail. Three types of vocal emissions were recorded: (1) 'peep', characterized by a repartition of energy over a wide range (0-50 kHz) of frequencies without any clear structure; (2) 'chatters', characterized by an audible (frequencies in hearing range of humans) fundamental frequency (2.47 +/- 0.03 kHz) and harmonics; and (3) 'ultrasonic emissions', characterized by a succession of slightly modulated pulses with frequencies in the 20-35 kHz range. Peeps and chatters were never recorded before the application of the stimuli. Several different vocalization patterns were described in terms of these types of responses. Just after the stimulation, all the animals emitted a 1st peep, which was generally (61%) followed by a 2nd one. They appeared with reproducible latencies, durations and envelopes. The envelopes of the audible (peeps and chatters) responses were intensity-dependent. Experimental data (moving the stimulation site, lidocaine injection) indicated that the 1st and 2nd peeps were triggered by two different groups of peripheral fibres with mean conduction velocities of 7.3 +/- 0.8 and 0.7 +/- 0.1 m/sec, respectively. This suggested an involvement of A delta and C fibres. Morphine showed a naloxone-reversible and dose-dependent antinociceptive effect by decreasing the 1st and 2nd peep envelopes. It is concluded that a short stimulus applied to the tail triggers a complex behavioural repertoire. It is proposed that this model will be a useful tool for physiological and pharmacological studies of nociception.

Anesthetics, Local↗
PubMed1995

The spinal transmission of nociceptive information: modulation by the caudal medulla.

Multiple descending systems for pain control originate from the rostral medulla and midbrain. These systems are involved in the antinociceptive action produced by opioids. One category of descending inhibitory controls is activated specifically by noxious stimuli and has been termed diffuse noxious inhibitory controls. These controls have been described in both animal and man, but their supraspinal circuitry has not been fully localized. To determine the supraspinal level of integration of nociceptor activated controls and hence their potential relationships with previously described descending controls, we studied in halothane-anesthetized rats the effects of transections performed at various levels in the brainstem. The physiological properties of dorsal horn convergent neurons, including supraspinally-mediated inhibitory processes elicited by heterotopic noxious stimuli, i.e. diffuse noxious inhibitory controls, were not altered in rats in which the brainstem had been completely transected up to 200 microns caudal to the caudal end of the rostral ventromedial medulla. In contrast, the spontaneous activity of these neurons was significantly enhanced and the inhibitory phenomena significantly reduced in animals with transections more than 500 microns caudal to the caudal end of the rostral ventromedial medulla. These effects were not related to cardiovascular changes induced by the transections. These data indicate that some tonic descending inhibitory controls and diffuse noxious inhibitory controls depend upon connections in the caudal medulla. It is proposed that this area constitutes another level from which the transmission of nociceptive information can be modulated and that it acts co-operatively with previously described modulatory systems in the spinal cord and at more rostral levels of the brainstem.

Animals↗
PubMed1995

Oligopeptides are the main source of nitrogen for Lactococcus lactis during growth in milk.

The consumption of amino acids and peptides was monitored during growth in milk of proteinase-positive (Prt+) and -negative (Prt-) strains of Lactococcus lactis. The Prt- strains showed monophasic exponential growth, while the Prt+ strains grew in two phases. The first growth phases of the Prt+ and Prt- strains were in same, and no hydrolysis of casein was observed. Also, the levels of consumption of amino acids and peptides in the Prt+ and Prt- strains were similar. At the end of this growth phase, not all free amino acids and peptides were used, indicating that the remaining free amino acids and peptides were unable to sustain growth. The consumption of free amino acids was very low (about 5 mg/liter), suggesting that these nitrogen sources play only a minor role in growth. Oligopeptide transport-deficient strains (Opp-) of L. lactis were unable to utilize oligopeptides and grew poorly in milk. However, a di- and tripeptide transport-deficient strain (DtpT-) grew exactly like the wild type (Opp+ Dtpt+) did. These observations indicate that oligopeptides represent the main nitrogen source for growth in milk during the first growth phase. In the second phase of growth of Prt+ strains, milk proteins are hydrolyzed to peptides by the proteinase. Several of the oligopeptides formed are taken up and hydrolyzed internally by peptidases to amino acids, several of which are subsequently released into the medium (see also E.R.S. Kunji, A. Hagting, C.J. De Vries, V. Juillard, A.J. Haandrikman, B. Poolman, and W.N. Konings, J. Biol. Chem. 270:1569-1574, 1995).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1995

Effects of intrathecal and intracerebroventricular buprenorphine on a C-fiber reflex in the rat.

A C-fiber reflex elicited by electrical stimulation within the territory of the ipsilateral sural nerve, was recorded from the biceps femoris muscle in anesthetized rats. The temporal evolution of the reflex was studied using a constant level of stimulus intensity (3 x threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. Intrathecal doses of buprenorphine in the 0.2 to 10 micrograms range, elicited a facilitation of the C-fiber reflex in a dose-dependent manner. A large dose (100 micrograms) depressed but did not block the reflex. Intracerebroventricular doses of buprenorphine in the 0.1 to 10 micrograms range, facilitated the C-fiber reflex. A higher dose (100 micrograms) elicited a biphasic effect: depressive when the stimulus intensity was weak and facilitatory when the stimulus intensity was strong. It is concluded that the antinociceptive properties of buprenorphine cannot be related to a direct or indirect depressive spinal effect. In terms of spinal and supraspinal effects of buprenorphine, it is likely that buprenorphine facilitates the C-fiber reflex via a supraspinal mechanism that acts on sensory and/or motor components of the reflex arc although the depression of the reflex involves a spinal mechanism. The lipophilic properties of buprenorphine could explain a substantial diffusion from its spinal injection site to the brain. From a clinical standpoint, this study confirms that intrathecal administration of buprenorphine is an inadequate way of accessing spinal opioid receptors.

Analgesics, Opioid↗
PubMed1995

Effects of intravenous morphine and buprenorphine on a C-fiber reflex in the rat.

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied by using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying the stimulus intensity from 0 to 7 x threshold. Low (0.5-1 mg/kg) and high doses (4-10 mg/kg) of i.v. morphine induced a facilitation and a depression of the C-fiber reflex, respectively, in a dose-dependent manner. The ED50 (95% confidence limit) for the depressive effect with a stimulus intensity of 3 x control threshold was 3.8 (3.1-4.8) mg/kg. Increasing the stimulus intensity was associated with a shift of the dose-response curve to the right, without a change of slope. In the 1.5 to 7 x threshold range, ED50 were linearly related to the stimulus intensity. Intravenous naloxone (0.4 mg/kg) completely antagonized the facilitation or depression induced by morphine. Low doses (1-10 micrograms/kg; i.v.) of buprenorphine facilitated the reflex in a fashion similar to morphine. Higher doses (30-1000 micrograms/kg; i.v.) elicited a biphasic effect on the C-fiber reflex: depressive and facilitatory with weak and strong stimulus intensities, respectively. These results are discussed in terms of there being an intrinsic efficacy for the depressive effects of morphine and buprenorphine and of their clinical potencies. Various hypotheses are suggested regarding the facilitations of the C-fiber reflex.

Animals↗
PubMed1995

The activation of bulbo-spinal controls by peripheral nociceptive inputs: diffuse noxious inhibitory controls.

Some neurones in the dorsal horn of the spinal cord are strongly inhibited when a nociceptive stimulus is applied to any part of the body, distinct from their excitatory receptive fields. This phenomenon was termed "Diffuse Noxious Inhibitory Controls" (DNIC). DNIC influence only convergent neurones, and these inhibitions can be triggered only by conditioning stimuli which are nociceptive. The inhibitions are extremely potent, affect all the activities of the convergent neurones and persist after the removal of the conditioning stimulus. Only activity of A delta- or A delta- and C- peripheral fibres can trigger DNIC. DNIC are sustained by a complex loop which involves supraspinal structures since, unlike segmental inhibitions, they are not observed in animals in which the cord has previously been transected at the cervical level. The ascending and descending limbs of this loop travel respectively through the ventro-lateral and dorso-lateral funiculi, respectively. We proposed that DNIC result from the physiological activation of some brain structures putatively involved in descending inhibition. However, lesions of the mesencephalon, including the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM), including nucleus raphé magnus, did not modify DNIC. By contrast, lesions of subnucleus reticularis dorsalis (SRD) in the caudal medulla strongly reduced DNIC. Both electrophysiological and anatomical data support the involvement of SRD neurones in spino-bulbo-spinal loop(s). In man, very similar results have been obtained by means of combined psychophysical measurements and recordings of nociceptive reflexes (RIII reflex). Painful heterotopic conditioning stimuli depress both the reflex and the associated painful sensation, with stronger effects being observed with more intense conditioning stimuli. By contrast, in tetraplegic patients, heterotopic nociceptive stimulation did not produce any depression of the RIII reflex. Observations were also made on patients with cerebral lesions causing contralateral hemi-analgesia, either a unilateral thalamic lesion or a lesion of the retro-olivary part of the medulla (Wallenberg's syndrome). In the patients with Wallenberg's syndrome, no inhibitions were observed when the nociceptive conditioning stimuli were applied to the affected side whereas if these stimuli were applied to the normal side they triggered inhibitory effects and post-effects very similar to those seen in normal subjects. These results show that in humans, brainstem--probably reticular--structures seem to play a key role in these phenomena. The data suggest that nociceptive stimuli, even though there are unquestionably perceived as being painful activate certain inhibitory controls which originate in the brainstem. Since all convergent neurones are subject to DNIC, one can make the assertion that the transmission of nociceptive signals towards higher centres is under the influence of these controls. In other words, the descending inhibitory controls may play a physiological role in the detection of nociceptive signals. It is proposed that DNIC constitute both a filter which allows the extraction of the signal for pain and an amplifier in the transmission system which increases the potential alarm function of the nociceptive signals. This hypothesis is supported by the finding that DNIC are blocked by low doses of morphine in both rat and man.

Animals↗
PubMed1994

Effects of heterotopic noxious stimuli on activity of neurones in subnucleus reticularis dorsalis in the rat medulla.

1. In anaesthetized rats, recordings were made in the medullary subnucleus reticularis dorsalis. Neurones with total nociceptive convergence (TNC) responded to percutaneous electrical stimuli with early and late peaks due to the activation of A delta and C fibres respectively, no matter which part of the body was stimulated. Neurones with partial nociceptive convergence (PNC) responded with an A delta peak regardless of which part of the body was stimulated, and with a C peak of activation from some, mainly contralateral, parts of the body. 2. All TNC neurones responded to noxious thermal stimulation of the limbs with a phasic discharge followed by tonic activity that lasted throughout the stimulation. Discharges elicited by applying stimuli simultaneously to both forepaws or to a hindpaw and a forepaw were lower than the individual responses to stimulation of a single limb. Similar negative interactions were observed in the responses of PNC neurones following noxious thermal stimulation of two paws. 3. In both neuronal populations, the simultaneous application of noxious thermal stimuli and microelectrophoretic application of D,L-homocysteic acid (DLH) induced responses of greater magnitude than those evoked by each stimulus alone. 4. TNC neurones responded to electrical stimulation of the contralateral hindpaw with A delta and C fibre responses. Noxious thermal stimuli applied to different areas of the body induced an excitatory response during the period that preceded the electrical stimulation, but an inhibition of both A delta and C fibre responses. By contrast, using a similar protocol, application of DLH induced a steady discharge in the period preceding the electrical stimulation and also in between the A delta and C fibre responses, which were not themselves inhibited. 5. The negative heterotopic influences in normal rats during simultaneous immersion of the ipsi- and contralateral hindpaws was strongly reduced in rats with bilateral lesions of the dorsolateral funiculi at the cervical level (C3-C4). 6. It is concluded that strong negative interactions elicited by heterotopic noxious stimuli are observed in the spinoreticular system. Such interactions do not occur at the subnucleus reticularis dorsalis level but are mediated by supraspinal structures which control, through the dorsolateral funiculi, the spinal transmission of nociceptive information.

Animals↗
PubMed1994

Inhibition of a somatic nociceptive reflex by gastric distention in humans.

BACKGROUND/AIMS: The spinal nociceptive RIII reflex, an exteroceptive cutaneous-muscular flexion reflex, is powerfully and specifically inhibited by painful heterotopic somatic stimuli. The aim of the present study was to evaluate the effects of nonpainful and painful visceral stimuli on this reflex. METHODS: In nine healthy volunteers, the effects of five levels of gastric distention were tested on the RIII reflex, recorded from the biceps femoris, and elicited by electrical stimulation of the ipsilateral sural nerve. Distentions were performed by means of a balloon that was placed in the proximal part of the stomach and connected to an electronic barostat. The sensations evoked by gastric distention were scored using a graded (0-6) questionnaire. RESULTS: The 200- and 400-mL distention levels elicited no significant modifications of the RIII reflex; the 600-, 800-, and 1000-mL levels inhibited the RIII reflex by 25%, 35%, and 55%, respectively. The magnitude of this inhibition correlated significantly (P < 0.0001) with both the level of distention and the intensity of visceral perception. CONCLUSIONS: Gastric distention produces volume-dependent inhibition of the somatic RIII reflex in humans. This model may provide an interesting tool for objective and quantitative evaluation of normal and disturbed visceral sensations in humans.

Adult↗
PubMed1994

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. Part I: Brain glucose metabolism is increased after GABAA receptors activation.

Though gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the human central nervous system, the metabolic response to GABA system activation remains imperfectly known. We studied in vivo with positron emission tomography (PET) the variations of glucose metabolism in the human brain after stimulation of the GABAA receptors by systemic administration of the specific GABAA agonist, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP). These investigations were performed in three normal volunteers and as part of presurgical evaluation for temporal lobe epilepsy in six patients. While clinical and electroencephalographic (EEG) monitoring showed a sedative effect and sleepiness after THIP administration, glucose metabolism was paradoxically increased in grey matter structures, which are known to have a high density of GABAA receptors. These findings suggest that the pharmacological activation of GABA pathways, although inhibitory and producing a decrease of vigilance, increases the energetic demand at least during a phase of GABA agonist action, probably at the synaptic or at the glial cell level.

Adult↗
PubMed1994

Effects of GABAA receptors activation on brain glucose metabolism in normal subjects and temporal lobe epilepsy (TLE) patients. A positron emission tomography (PET) study. Part II: The focal hypometabolism is reactive to GABAA agonist administration in TLE.

Positron emission tomography (PET) using [18F]fluorodeoxyglucose (FDG) was used to study the metabolic response of focal hypometabolism to the administration of a specific GABAA agonist (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), THIP, in six temporal lobe epilepsy (TLE) patients. After THIP injection, the increase of glucose metabolism in the hypometabolic focus was larger than the mean increase reported in the whole brain (Part I; Epilepsy Res., 19 (1994) 45-54). Within the hypometabolic focus, this increase was significantly higher in regions with the lowest basal metabolic level. This metabolic response in the hypometabolic focus, observed in the absence of any epileptic discharge during FDG accumulation and PET data acquisition, suggests that GABAA receptors are up-regulated or, at least, preserved in TLE.

Adult↗
PubMed1994

A C-fiber reflex modulated by heterotopic noxious somatic stimuli in the rat.

1. Electromyographic recordings were made from the biceps femoris muscle through a pair of noninsulated platinum/iridium needle electrodes in male Sprague-Dawley rats artificially ventilated and anesthetized with 0.8% halothane in a N2O-O2 mixture (2/3:1/3). The animals' ventilation, heart rates, and body temperatures were continuously monitored. Electrical stimuli (2-ms duration, 0.16 Hz) were delivered to the sural nerve territory through a pair of noninsulated platinum/iridium needle electrode inserted subcutaneously in the medial aspect of the 4th and the lateral part of the 5th toe. Such stimulation elicited a two-component reflex response in the ipsilateral biceps femoris muscle: The first had a short latency (17.5 +/- 2.3 ms), short duration (20.7 +/- 2.6 ms), and low threshold (1.5 +/- 0.6 mA), whereas the second had a longer latency (162.4 +/- 5.1 ms), longer duration (202.3 +/- 6.2 ms), and higher threshold (5.7 +/- 0.5 mA). 2. Lidocaine (0.02-0.1%; 0.1 ml), but not saline, injected subcutaneously over the proximal part of the sural nerve, produced a selective depression of the late component of the reflex response, whereas the first component remained unchanged. The conduction velocity of the afferent fibers was estimated from the stimulation needles in the sural nerve territory to the nerve's projection in the lumbar spinal cord: it was concluded that the second, late component of the reflex response was due to afferent signals transmitted via unmyelinated C-fibers, whereas the first component was related to activation of fine myelinated fibers (A delta group). 3. Electrical stimulation of the sural nerve was still able to elicit the two-component reflex responses in the ipsilateral biceps femoris muscle of chronic spinal rats, indicating that these responses were genuine reflex responses, transmitted completely through a spinal circuit. 4. The C-fiber reflex was recorded when the duration and frequency of the stimuli applied to the sural nerve varied within the 0.5- to 4-ms and 0.02- to 1-Hz ranges, respectively. It was concluded that a single 2-ms duration shock at an intensity of 1.2 times the C-fiber reflex threshold, delivered every 6 s (0.16 Hz), constituted an acceptable and optimal protocol for experiments in which the C-fiber reflex was studied as a function of time. These parameters were used throughout the subsequent experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1994

Effects of mu, delta and kappa opioid antagonists on the depression of a C-fiber reflex by intrathecal morphine and DAGO in the rat.

The roles of mu, delta and kappa opioid receptor subtypes in spinal morphine-induced antinociception were investigated. A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. Recruitment curves were built by varying the stimulus intensity from 0 to 7x threshold and temporal evolutions were studied by using a constant level of stimulus intensity (3x threshold). Intrathecal administration of naloxone, Cys2-Tyr3-Orn5-Pen7 amide (mu opioid receptor antagonist) and nor-binaltorphimine (nor-BNI, a kappa opioid receptor antagonist) completely antagonized the depression of the C-fiber reflex induced by 4 nmol of intrathecal morphine, whereas the antagonistic effect of naltrindole (a delta receptor antagonist) was limited, with a ceiling effect of 56%. The AD50 were 12 pmol and 1, 4.3 and 39 nmol for Cys2-Tyr3-Orn5-Pen7 amide, naloxone, nor-BNI and naltrindole, respectively. When injected alone, only naltrindole induced a short-duration depressive effect. Intrathecal administration of DAGO resulted in a depressive effect on the C-fiber reflex in a dose-dependent manner; for a stimulus intensity of 3x threshold, the ED50 was 9 pmol. DAGO was found to be 60 times more potent than morphine. Interestingly, nor-BNI, at doses which reversed the blockade of the C-fiber reflex by morphine, also reversed the effects of an equipotent dose of DAGO, which suggested an action on a mu receptor subtype.

Animals↗
PubMed1993

A sensitive test for studying the effects of opioids on a C-fibre reflex elicited by a wide range of stimulus intensities in the rat.

A C-fibre reflex elicited by electrical stimulation within the receptive field of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anaesthetized rats. Recruitment curves were built by varying the stimulus intensity from 0 to 50 mA and temporal evolution was studied by using a constant level of stimulation. At a constant level of stimulation, intrathecal administration of morphine resulted in a depressive effect on the C-fibre reflex in the 0.18-0.75 microgram range (ED50 = 0.2 microgram). Study of the recruitment curves showed that, in the 0.18-0.375 microgram range, morphine had little effect on the threshold, but induced significant decreases in the slopes. At doses above 0.75 microgram, morphine modified both the threshold and the slope of the recruitment curves. Systemic naloxone totally reversed these effects. It is concluded that intrathecal morphine not only produces a shift in the encoding functions of the spinal cord but also reduces the gain of these functions. It is suggested that this method is reliable for the pharmacological study of the spinal transmission of nociceptive signals.

Analysis of Variance↗
PubMed1993

Opioid control of the release of calcitonin gene-related peptide-like material from the rat spinal cord in vivo.

The possible control by opioids of the spinal release of calcitonin gene-related peptide-like material (CGRPLM) was investigated in halothane-anaesthetized rats whose intrathecal space was perfused with an artificial cerebrospinal fluid. Morphine (20 mg/kg i.v.; or at 10-100 microM added to the perfusing fluid), the mu selective agonist DAGO (10 microM) and the kappa selective agonist U 50488 H (10 microM) did not affect the spontaneous outflow of the CGRPLM. In contrast, the selective delta agonist DTLET (10 microM) significantly increased CGRPLM release. The latter effect could be prevented by the selective delta antagonist naltrindole (10 microM) as expected from the involvement of this class of opioid receptors. However, the addition of naltrindole alone to the perfusing fluid did not modify CGRPLM outflow, indicating that endogenous opioids do not exert a tonic control of CGRP-containing fibers through the stimulation of delta receptors. In contrast, intrathecal perfusion with naloxone (10 microM) or nor-binaltorphimine (10 microM), a selective antagonist of kappa receptors, produced a marked increase in spinal CGRPLM release, suggesting that endogenous opioids acting at mu and kappa receptors, respectively, exert a tonic inhibitory control of CGRP-containing fibers. Indeed, a significant decrease in the spinal release of CGRPLM release could be evoked by the combined addition of U 50488 H (10 microM) plus DAGO (10 microM) to the perfusing medium, indicating that the simultaneous stimulation of both kappa and mu receptors is required for this negative control to occur. This could notably be achieved with morphine (10 microM) in the presence of naltrindole (10 microM) which also produced a significant reduction in the spinal release of CGRPLM. In conclusion, morphine per se did not change CGRPLM release because this drug triggers opposite positive (through the stimulation of delta receptors) and negative (through the concomitant stimulation of both kappa and mu receptors) control mechanisms within the rat spinal cord.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Morphine and diffuse noxious inhibitory controls in the rat: effects of lesions of the rostral ventromedial medulla.

The aim of this study was to investigate whether the rostral ventromedial medulla (RVM) participates in the lifting of diffuse noxious inhibitory controls (DNIC) by systemic morphine. The effects of morphine (1 mg/kg i.v.) on DNIC were compared in sham-operated rats and animals with electrolytic lesions of the RVM performed one or three weeks earlier. The C-fibre-evoked responses of spinal dorsal horn convergent neurones were similar in the sham-operated and lesioned animals. DNIC acting on these responses were also similar in these groups. DNIC were similarly reduced naloxone reversibly following morphine injections in sham-operated animals and animals tested one week after lesioning of the RVM. In contrast, DNIC were not significantly altered by morphine in animals tested three weeks after lesioning. The lesions were similar in both groups of animals. This time-dependent attenuation of the effects of morphine indicates that the RVM is not directly involved in the reduction of DNIC induced by systemic morphine. However, it is suggested that lesions in this region can induce a reorganization of brainstem opioidergic systems.

Analgesics↗