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Biomedical subjects

D Le Bars

Publications and source records attributed to D Le Bars.

At least 127 records · Page 7Linked to original sources
PubMed1988

Spontaneous and evoked release of met-enkephalin-like material from the spinal cord of arthritic rats in vivo.

Perfusion of the intrathecal space with artificial CSF was achieved in control and arthritic rats under halothane anaesthesia in order to collect the met-enkephalin-like material (MELM) released from the whole spinal cord. On the fourth week following the intradermal injection of Freund's adjuvant to induce arthritis, a marked reduction (-56%) in the spontaneous outflow of MELM was noted in arthritic rats. This effect did not involve changes in the degradation process of MELM, since it persisted when kelatorphan was added to the perfusing fluid in order to inhibit completely the peptidases acting on met-enkephalin. Raising the K+ concentration in the perfusing fluid from 2.4 to 40 mM, as well as moving the hind paws, produced a significant enhancement of MELM release which was (at least) as pronounced in arthritic as in control rats. These results suggest that the basal activity of spinal enkephalinergic neurones, but not that triggered by various stimuli, is reduced in arthritic rats.

Animals↗
PubMed1988

Radiosynthesis of NCA [carbonyl-11C]6-fluoromelatonin.

A method is described for the preparation of [carbonyl-11C]6-fluoromelatonin for intravenous injection and potential study of the melatonin system in vivo by positron emission tomography. The preparation is based on the acetylation of 6-fluoro-5-methoxytryptamine with NCA [1-11C]acetyl chloride (itself prepared from cyclotron-produced [11C]carbon dioxide) and purification by HPLC. It gives chemically and radiochemically pure [carbonyl-11C]6-fluoromelatonin in 35% radiochemical yield (from [11C]CO2, decay-corrected) within 35 min from the end of radionuclide production and with high specific activity e.g. 1.6 GBq/mumol (43 mCi/mumol) at the end of synthesis from 1.1 GBq (30 mCi) of [11C]carbon dioxide.

Carbon Radioisotopes↗
PubMed1988

Convergence of heterotopic nociceptive information onto subnucleus reticularis dorsalis neurons in the rat medulla.

1. In anesthetized rats recordings were made from neurons in the medulla caudal to the obex. In the medullary dorsal horn, typical trigeminal noxious specific, nonnoxious specific, and convergent neurons were found. In nucleus cuneatus, typical dorsal column units were recorded. In subnucleus reticularis dorsalis (SRD), recordings were made from neurons which exhibited convergence of nociceptive inputs from the entire body. In subnucleus reticularis ventralis (SRV) we recorded both from neurons with spontaneous activity that were either unaffected or inhibited by noxious stimuli applied to various parts of the body and from respiratory neurons. The present paper deals particularly with the nature of the stimuli that activated reticular neurons exhibiting nociceptive convergence. 2. Neurons with nociceptive convergence could be activated by mechanical, thermal, or chemical noxious stimuli applied to widespread areas of the body. By using percutaneous electrical stimulation, we found that they responded to the activation of peripheral fibers in the A delta- and C-range. Two neuronal subpopulations were defined according to the way in which SRD neurons responded to the electrical stimuli, namely: "neurons with total nociceptive convergence" (TNC) and "neurons with partial nociceptive convergence" (PNC). 3. The great majority (84%) of TNC neurons did not exhibit spontaneous activity and none of these neurons gave responses to heterosensory (flashes, whistle sounds) or proprioceptive stimuli. Most (88%) did not respond to any kind of innocuous cutaneous stimuli. By contrast, the entire population of TNC neurons responded to noxious mechanical, thermal, and visceroperitoneal stimuli. In the majority of cases (71%) long-lasting afterdischarges were observed following cessation of the application of the nociceptive stimulus. 4. All the TNC neurons responded to suprathreshold percutaneous electrical stimulation (2-ms duration) with two peaks of activation no matter which part of the body was stimulated. By stimulating two regions of the tail, 100 mm apart, we determined that the early and late peaks of activation were triggered by activities in peripheral fibers with mean conduction velocities of 10.8 +/- 0.5 and 0.74 +/- 0.05 (SE) m/s, respectively, i.e., A delta- and C-fibers. The mean thresholds for obtaining A delta-fiber components were found in the 0.4-0.7-mA range; the mean thresholds for obtaining C-fiber components were found in the 6-7.5- and 3-4-mA range for the face and the other parts of the body, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

[Convergence of heterotopic nociceptive information onto neurons of the subnucleus reticularis dorsalis in the rat].

The nature of stimuli that activate neurones located within the Subnucleus Reticularis Dorsalis (SRD) was determined. These neurones do not respond to visual, auditory or proprioceptive stimuli but are preferentially or even exclusively activated by noxious stimuli applied to any part of the body; only neurones of a sub-group have a predominantly contralateral activation. All the neurones were exclusively activated by stimulation of A delta or A delta and C afferent fibres. These observations suggest that this well-delimited reticular structure is specifically involved in the processing of nociceptive information.

Animals↗
PubMed1988

Intracerebroventricular morphine decreases descending inhibitions acting on lumbar dorsal horn neuronal activities related to pain in the rat.

Recordings were made from convergent neurons in the lumbar dorsal horn of the rat. These neurons were activated by both innocuous and noxious stimuli applied to their excitatory receptive fields located on the extremity of the ipsilateral hindpaw. Transcutaneous application of suprathreshold 2-msec square-wave pulses to the center of the receptive field resulted in responses to A- and C-fiber activation being observed: 27.2 +/- 2.2 (mean +/- S.E.M.) C-fiber latency spikes were evoked per stimulus. This type of response was inhibited by applying noxious conditioning stimuli to heterotopic areas of the body; in particular, immersing the tail in a 52 degrees C waterbath caused a 74.2 +/- 2.0% inhibition of the C-fiber evoked responses; such inhibitory processes have been termed diffuse noxious inhibitory controls (DNIC). The effects of microinjections of morphine (0.6-40 micrograms; 2 microliter) within the 3rd ventricle on both the unconditioned C-fiber-evoked responses and the inhibitory processes triggered from the tail were investigated in an attempt to answer two questions: 1) does i.c.v. morphine increase tonic descending inhibitory processes? and 2) what are the effects of i.c.v. morphine on descending inhibitory processes triggered phasically by noxious stimuli? The predominant effect of i.c.v. morphine on the C-fiber-evoked responses was a facilitation (17 of 26 cases). Such a facilitation was dose-related in the 0.6 to 40 microgram range and naloxone reversible; it plateaued from 20 min after the microinjection. No clear relationship was found between the number of C-fiber evoked responses in the control sequences and the subsequent effect of i.c.v. morphine. Intracerebroventricular morphine clearly reduced DNIC in the majority of cases (21 of 26). Such a reduction was dose-related in the 0.6 to 2.5 microgram range and naloxone reversible; it plateaued within 90 min of microinjection. No clear relationship was found between the changes in DNIC and either the number of C-fiber-evoked spikes in the control sequences or the changes in the C-fiber responses induced by i.c.v. morphine. Autoradiographic controls using [3H]morphine showed a labeling along the ventricle wall including the hypothalamus, the periaqueductal gray matter and the floor of the 4th ventricle, three regions which have been implicated in the control of nociceptive transmission at the spinal level. Diffusion from the ventricle wall was over a distance of 0.5 mm and was identical whether observed 20 or 95 min after the microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Involvement of the dorsolateral funiculi in the spinal release of Met-enkephalin-like material triggered by heterosegmental noxious mechanical stimuli.

The lumbar spinal cord was superfused with artificial CSF at a rate of 0.1 ml/min in halothane anaesthetized rats. Under resting conditions, Met-enkephalin-like material (MELM) found in superfusates corresponded to a spinal release of 4.2 +/- 1.4 pg Met-enkephalin equivalents per 5 min. During a 30-min period in which pinches were applied to the muzzle, the MELM content in the superfusates increased markedly (by 120.5 +/- 32.9%). This effect was totally suppressed following bilateral lesions of the dorsolateral funiculi (DLF), under both chronic and acute conditions. It is concluded that strong mechanical stimuli applied in the trigeminal region can induce the release of MELM within the lumbar spinal cord via mechanisms involving the DLF. This heterosegmental release of Met-enkephalin may participate in the management of pain by methods involving high intensity stimulation.

Animals↗
PubMed1987

Noxious mechanical stimuli increase the release of Met-enkephalin-like material heterosegmentally in the rat spinal cord.

Although the physiological functions of the endogenous opioid systems are not yet clearly established, it is widely accepted that they exert an inhibitory control on pain transmission. However, the well-documented hypoalgesic effects of low doses of the opiate antagonist naloxone both in animals and humans do not fit in with this concept. The present investigations, at two different spinal/medullary levels (viz. cervicotrigeminal and lumbar) demonstrate that, in the rat, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM) from neural segments related to the stimulated area of the body, but does increase its release from other segments. Electrophysiological studies have already demonstrated the existence of such heterosegmental mechanisms, notably 'diffuse noxious inhibitory controls' (DNIC), which are naloxone-reversible and could play an important role in pain perception. The involvement of spinal enkephalins in DNIC would seem to mean that the heterosegmental spinal release of MELM triggered by noxious stimuli participates in pain processes.

Animals↗
PubMed1987

Parallel clinical and behavioural studies of adjuvant-induced arthritis in the rat: possible relationship with 'chronic pain'.

The course of adjuvant-induced arthritis was followed, over an 11-week postinoculation period, in Sprague-Dawley rats, using both clinical and behavioural methods of study. Clinical observations included body weight, diameters of radiocarpal and tibiotarsal joints and radiological analysis of forepaws, hindpaws and vertebrae. Behavioural observations included those of spontaneous behaviour-mobility, exploring, rearing, penis licking and scratching-and of pain-related tests-the foot-bend procedure and Randall-Selitto test. In general, the time course of the disease could be divided into 4 stages, viz. a preclinical, an acute, a postacute and a recovery stage. The preclinical stage (first week) was characterized by discrete radiological lesions of the forepaws and a slight increase in the threshold for struggle triggered by foot pressure, but, above all, by no change in the other parameters. The acute stage (weeks 2-4) was clearly defined by a pause in body weight gain and by dramatic behavioural changes: a lack of mobility and exploring behaviour, a profound increase in scratching behaviour and signs of hyperalgesia. During this period, hindpaw and forepaw joint diameters increased dramatically. The behavioural modifications peaked at the same time (week 4) as there was an acceleration in the radiological abnormalities (soft tissue swelling, demineralization and erosion of bone extremities and joint space narrowing) which had begun during week 3. During the postacute stage (weeks 5-8), body weight and behavioural reactions began to return towards control values, but joint diameters and radiological scores either continued to increase or remained constant. During the recovery stage (weeks 9-11), behavioural scores and body weight returned to control values while the mean joint diameters remained constant and there was a slight decrease in the radiological scores. In spite of the complexity of the model used in these studies, it appeared quite clear that the acute phase of the disease was characterized by the onset of clinical symptoms and dramatic changes in behaviour, all of which could be related to the occurrence of pain; signs of pain were still present, albeit weaker, in the postacute phase. Such observations, taken together, help to validate adjuvant arthritis as an experimental model of chronic pain in Sprague-Dawley rats.

Animals↗
PubMed1987

The preparation of a carbon-11 labelled neurohormone--[11C]melatonin.

Melatonin, a hormone of the pineal gland, has been labelled with the positron-emitting radionuclide, carbon-11 (t1/2 = 20.4 min), for study in vivo by positron emission tomography. Thus a novel labelling agent, [11C]acetyl chloride, was prepared by the carbonation of methylmagnesium bromide with cyclotron-produced [11C]carbon dioxide followed by treatment with phthaloyl dichloride. Acylation of 5-methoxytryptamine then affords [11C]melatonin, which is purified by HPLC and formulated for intravenous injection. The preparation requires 35 min from the end of radionuclide production. It provides [11C]melatonin in 13% radiochemical yield (decay-corrected from 11CO2) and in high specific activity. Radiochemical and chemical purity were demonstrated by HPLC and TLC. The validity of the radiosynthesis was also confirmed by a parallel synthesis of [13C]melatonin and examination of the product by 13C-NMR spectroscopy and mass spectrometry.

Carbon Dioxide↗
PubMed1987

An electrophysiological investigation into the pain-relieving effects of heterotopic nociceptive stimuli. Probable involvement of a supraspinal loop.

It has previously been shown that, in normal subjects, heterotopic painful stimuli induce parallel decreases in the sensation of pain and the nociceptive spinal flexion reflex RIII simultaneously evoked by electrical stimulation of the sural nerve. By contrast, heterotopic non-noxious stimuli were ineffective in this respect. In order to assess the possible involvement of supraspinal structures in these changes, we have now compared the effects of nociceptive electrical stimuli applied to the fourth and fifth fingers of the hand on the contralateral RIII reflex in 5 normal subjects and 5 tetraplegic patients suffering from a clinically complete spinal cord transection of traumatic origin. The tetraplegic patient had a C5, C6 or C7 spinal cord transection with lower segments, notably C8 and T1, clinically uninjured. In these patients, sural nerve stimulation induced a biceps femoris reflex which did not differ from the RIII reflex recorded in normal subjects, either in terms of latency or of threshold. In both groups, the RIII reflex threshold was determined and a juxta-threshold RIII reflex was studied before, during and after a 2 min period of conditioning stimulation. The conditioning procedure consisted of nociceptive electrical stimulation applied to the digital branches of the ulnar nerve which arises from C8 and T1, i.e., below the level of the patients' spinal transection. In normal subjects such conditioning elicited painful sensations of 'pin prick', 'burning' and 'squeezing'. It simultaneously induced a strong inhibition of the RIII reflex which outlasted the conditioning period by several minutes. By contrast, non-nociceptive electrical conditioning stimuli (0.1 ms duration pulses of 6 to 8 mA intensity, at 3/s), similarly applied to the digital branches of the ulnar nerve were totally ineffective. In tetraplegic patients not only was the RIII reflex never decreased by the heterotopic nociceptive stimulation but it was, in fact, slightly enhanced. These results show that the effects of heterotopic nociceptive stimulation observed in normal man are possibly mediated by a complex loop involving supraspinal structures. This further underlines the similarity between this phenomenon and the Diffuse Noxious Inhibitory Controls (DNIC) described in the rat, since the latter are observed in intact but not in spinal animals. These findings are discussed with reference to counter-irritation phenomena and procedures aimed at producing analgesia by somatic electrical stimulation.

Adult↗
PubMed1987

Lack of evidence for increased descending inhibition on the dorsal horn of the rat following periaqueductal grey morphine microinjections.

1 Recordings were made from 18 neurones in the dorsal horn of the rat, anaesthetized with halothane. All cells received A- and C-fibre inputs and responded to innocuous and noxious stimuli applied to their excitatory receptive fields located on the extremity of the ipsilateral hindpaw. Transcutaneous application of suprathreshold (mean 3.2 T) 2 ms square-wave pulses to the centre of the receptive fields resulted in responses to A- and C-fibre activation being observed; a mean 32.4 +/- 6.0 C-fibre latency spikes were evoked per stimulus. 2 A high dose (20 micrograms) of morphine in 0.5 microliter sterile saline, microinjected into the periaqueductal grey matter (PAG) had no effect on the C-fibre-evoked activity of thirteen cells (72%) and facilitated 5 neurones (28%). Microinjection sites covered most of the PAG particularly the caudal medioventral zone. 3 A relatively high dose (6 mg kg-1, i.v.) of systemic morphine chloride, sufficient to elicit the direct spinal action of the opiate, inhibited all 5 cells tested. 4 We conclude that there is little evidence that the supraspinal action of morphine includes increased descending controls and depression of dorsal horn neurones in the rat.

Animals↗
PubMed1987

Supraspinal morphine and descending inhibitions acting on the dorsal horn of the rat.

1. Recordings were made from thirty-nine convergent neurones in the lumbar enlargement of the rat spinal cord. These neurones were activated by both innocuous and noxious stimuli applied to their excitatory receptive fields located on the extremity of the ipsilateral hind paw. Transcutaneous application of suprathreshold 2 ms square-wave pulses to the centre of the receptive field resulted in responses to A- and C-fibre activation being observed; a mean of 18.8 +/- 1.8 C-fibre latency spikes was evoked per stimulus. This type of response was inhibited by applying noxious conditioning stimuli to heterotopic body areas; immersing the tail in a 52 degrees C water-bath caused a mean 54.5 +/- 2.3% inhibition of the C-fibre-evoked response; such inhibitory processes have been termed diffuse noxious inhibitory controls (d.n.i.c.). 2. The effects of microinjections of morphine (5 micrograms; 0.2 microliter) on both the unconditioned C-fibre-evoked response and inhibitory processes triggered from the tail were investigated in an attempt to answer two questions: (a) does morphine increase tonic descending inhibitory processes and (b) what are the effects of morphine on descending inhibitory processes triggered by noxious stimuli? 3. The predominant effect of periaqueductal grey matter (p.a.g.) morphine on the C-fibre-evoked responses was a facilitation: 51% of cells had their C-fibre-evoked responses increased by morphine (by roughly 50%); 31% of cells were not influenced while the remaining 18% of units were depressed; however the cells classified as depressed were only marginally so. No clear relationships were found either between the microinjection sites in the p.a.g. and their corresponding effects or between the number of C-fibre-spikes evoked in the control sequences and the subsequent effect of morphine. 4. While d.n.i.c. was not altered by morphine in 56% of cases, it was clearly reduced in the remaining cells. The effects were immediate but peaked at 40 min following the microinjection (a mean 77% reduction) and then returned towards control values. All but three of the corresponding microinjection sites were such as to include the medio-ventral p.a.g. including the nucleus raphé dorsalis. In contrast none of the cases where d.n.i.c. was unaltered included microinjection sites in this region. 5. No relationship was found between the changes in d.n.i.c. and the number of spikes evoked in the control sequences, or the changes in the C-fibre responses. 6. Autoradiographic controls using [3H]morphine showed a large diffusion of the drug within an area of about 0.75 mm around the tip of the cannula.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Heterotopic activation of A delta and C fibres triggers inhibition of trigeminal and spinal convergent neurones in the rat.

1. Extracellular recordings were made from fourteen non-noxious only and nineteen convergent neurones in trigeminal nucleus caudalis of halothane-anaesthetized rats. All the neurones studied were excited by the continuous micro-electrophoretic ejection of an excitatory amino acid, DL-homocysteic acid (DLH), with mean currents of 38.0 +/- 7.2 and 39.8 + 6.5 nA producing steady discharges of 35.0 +/- 3.3 and 31.8 +/- 1.3 spikes/s from the non-noxious only and convergent neurones respectively. 2. The repeated percutaneous application (100 trials; 0.66 Hz) of single square-wave stimuli (10 mA; 2 ms) to the tail always induced a biphasic depression of the activity of the convergent, but never of the non-noxious only, neurones. Both the early and late components of this inhibition occurred at shorter latencies when the base rather than the tip of the tail was stimulated. Differences in latencies from the two sites of stimulation (100 mm apart) were used to estimate the conduction velocities of the peripheral fibres which were triggering the inhibitions. 3. The cumulated results showed that, for the onset of the earlier component of the inhibition, the mean difference between the latencies from the two sites of stimulation was 13.6 +/- 1.9 ms, corresponding to a peripheral conduction velocity of 7.3 +/- 0.3 m/s, which is in the A delta-fibre range. For the onset of the late component of inhibition, the mean difference was 147.7 +/- 14.9 ms, corresponding to a peripheral conduction velocity of 0.68 +/- 0.07 m/s, which is in the C-fibre range. 4. When currents of different intensities were applied percutaneously to the two stimulation sites, the thresholds for obtaining the A delta component were in the range 0.25-0.5 mA whereas the C component appeared with currents 1-2 mA. A clear relationship between current intensity and magnitude of inhibition was observed in the 0.25-2 mA range for the A delta component and in the 1-5 mA range for the C component. 5. In an additional series of experiments recordings were made from eleven convergent neurones in the dorsal horn of the lumbar spinal cord. By using essentially the same experimental procedure the effects of repetitive application (100 trials, 0.66 Hz) of percutaneous electrical stimuli (1 or 10 mA, 2 ms) applied to the muzzle, were studied on the steady discharges (42.3 +/- 5.4 spikes/s) induced by DLH. The application of the 10 mA stimuli induced a biphasic depression of activity, whereas only an early component was observed following 1 mA stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Differential metabolic activity in the brain during deep halothane anesthesia. A qualitative study using [3H]deoxyglucose.

Alteration of metabolic activity during deep halothane anesthesia (3%) was analyzed qualitatively in the rat using a modified 2-deoxyglucose technique using the tritiated compound. The grey matter exhibited a homogeneous low level of metabolic activity in most places but some nuclei or subnuclear structures showed a much higher activity. These included in particular the locus coeruleus, the dorsal raphé, the substantia nigra pars compacta, the CA3 region of the hippocampus and the nucleus reticularis thalami. In the nucleus reticularis thalami, the use of 2-deoxy-[3H]glucose allowed us to demonstrate a high cellular metabolic activity, which is in agreement with several electrophysiological studies which showed a high rate of spontaneous activity under the same anesthetics.

Anesthesia, Inhalation↗
PubMed1986

Morphine antagonizes inhibitory controls of nociceptive reactions, triggered by visceral pain in the rat.

The interaction between morphine analgesia and the heterotopic hypoalgesic effects induced by visceral pain was investigated using a behavioral approach in the rat. Both systemic morphine and a dull pain of peritoneal-visceral origin (induced by i.p. phenylbenzoquinone, PBQ) increase the threshold for vocalization to tail-shock. The question of the interaction between these two factors was assessed by administering morphine during the period of increase in threshold induced by PBQ. Not only did we find that morphine did not increase the threshold further, but, indeed, very significantly decreased it, with the more obvious effect being observed for a moderate dose (0.33 mg/kg, i.v.). It is concluded that morphine antagonizes the heterotopic hypoalgesic effects of visceral pain. These results do not support the hypothesis that morphine increases inhibitory controls of pain triggered by noxious inputs.

Animals↗