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D Le Bars

Publications and source records attributed to D Le Bars.

At least 109 records · Page 6Linked to original sources

Efferent projections from the subnucleus reticularis dorsalis (SRD): a Phaseolus vulgaris leucoagglutinin study in the rat.

Small iontophoretic applications of Phaseolus vulgaris leucoagglutinin (PHA-L) were used in rats to study the efferent projections from a restricted region in the reticular formation of the caudal medulla: the subnucleus reticularis dorsalis (SRD). It was found that fibres from SRD project mainly to the spinal cord, the oral motor nuclei, the dorsal accessory inferior olive, the giganto- and parvo-cellular nuclei of the reticular formation and the parafascicular and ventromedian nuclei of the thalamus. Together with our previous electrophysiological findings, this study suggests that the SRD could be involved both in the control of pain processing and in motor reactions elicited by noxious events.

Afferent Pathways↗

Diffuse noxious inhibitory controls in man: involvement of an opioidergic link.

In man, heterotopic painful thermal conditioning stimuli induce parallel decreases in the spinal nociceptive flexion (RIII) reflex and the concurrent sensation of pain elicited by electrical stimulation of the sural nerve at the ankle. Such phenomena may be related to the diffuse noxious inhibitory controls (DNIC) which were initially described in the rat and subsequently documented in humans. In nine subjects in the present study, a 2-min application of a moderately noxious temperature (46 degrees C) to the contralateral hand strongly depressed the RIII reflex elicited in the biceps femoris muscle by electrical stimulation of the sural nerve at 1.2 times the reflex threshold. These depressive effects were maximal during the 2nd min of the conditioning period, showing an almost complete inhibition of the RIII reflex which gradually recovered its baseline value 6-9 min after the end of the conditioning period. Using a double-blind, cross-over design, it was found that these inhibitory effects were completely blocked 5 min after naloxone hydrochloride administration (0.4 mg i.v.) whereas the administration of saline was totally ineffective. The lifting of the inhibitions was compatible with the short duration of the pharmacological effects of naloxone in that the inhibitions were observed again 50 min after the naloxone injection. During all the experimental sessions, heart and respiratory rates remained stable at their control levels. It is concluded that the loop subserving DNIC which ascends from--and redescends to--the spinal cord involves an opioidergic link in man as in experimental animals. Possible implications for hypoalgesia based on the principles of counter-irritation or elicited by naloxone are discussed.

Adult↗

The intramyocardial fate of [1-14C] palmitate, iodopalmitate and iodophenylpentadecanoate in isolated rat hearts. A contribution to the choice of an iodinated fatty acid as a tracer of myocardial metabolism.

Labeled iodinated fatty acids (FAs) have been proposed to explore myocardial metabolism by external detection in man. We have chosen a 16-carbon FA, iodinated in omega position, whereas other authors use an iodophenylated FA. To explore the influence of the presence of an iodine or of an iodophenyl radical on the metabolism of the FA, we have compared, in isolated rat hearts perfused in a recirculating system, the intramyocardial fate of palmitate (PA), iodopalmitate (IPA), and iodophenylpentadecanoate (IPPA), the 3 of them being labeled with C14 in position 1. The addition of the iodine atom brings about a hindrance to the esterification of the FA into triglycerides, but not modification of the myocardial uptake and of the CO2 produced. The addition of the iodophenyl radical impairs both the FA storage and its oxidation, leading to a very high level of free FA. The phospholipid distribution is also modified. Apart from their myocardial use in the isolated rat heart, the 3 FAs were assayed in vitro as a substrate for acylCoA-synthase. As IPA more closely mimics native FA metabolism, it is therefore more suitable than IPPA as a tracer of myocardial metabolism.

Animals↗

Subcutaneous formalin induces a segmental release of Met-enkephalin-like material from the rat spinal cord.

The possible influence of a noxious chemical stimulus on the activity of spinal enkephalinergic neurones was examined by measuring the outflow of Met-enkephalin-like material (MELM) in CSF perifusates from the lumbar and cervico-trigeminal zones in halothane-anaesthetized rats. Following subcutaneous injection of 50 microliters of a 10% formalin solution in saline into the muzzle, MELM outflow increased at the cervico-trigeminal level but not at the lumbar level. Conversely, a significant enhancement in MELM outflow occurred at the lumbar but not at the cervico-trigeminal level when formalin was injected into a hind paw. In both cases, the increase in MELM release took place 5-10 min after the treatment and was of short duration (5-10 min). It is concluded that noxious chemical stimuli can induce a transient activation of enkephalinergic neurones within spinal zones receiving the nociceptive inputs. The marked differences in the characteristics of spinal MELM overflow due to noxious chemical, thermal and mechanical stimuli further support the notion that each type of nociceptive stimulus probably activates spinal enkephalinergic systems by triggering distinct neuronal mechanisms.

Animals↗

Acupuncture and diffuse noxious inhibitory controls: naloxone-reversible depression of activities of trigeminal convergent neurons.

Recordings were made from convergent neurons in trigeminal nucleus caudalis of the rat. These neurons could be activated by both innocuous and noxious mechanical stimuli applied to their excitatory receptive fields on the ipsilateral part of the muzzle. Percutaneous application of suprathreshold, 2 ms square-wave electrical stimuli to the centre of the excitatory field resulted in responses to A- and C-fibres being observed. The effects on these responses of manual acupuncture performed by a traditional Chinese acupuncturist at the "Zusanli" point on the right hindlimb were compared with the effects induced by acupuncture applied at a non-acupoint, next to "Zusanli". In addition, the effects of acupuncture were compared with the inhibitory effects evoked by noxious thermal stimulation of the left hindlimb on the responses of the same neurons. This last type of inhibition has been described previously by our group and termed diffuse noxious inhibitory controls. Acupuncture, either applied at "Zusanli" or at a non-acupoint and noxious thermal stimulation induced similar strong inhibitory effects on the C-fibre-evoked responses of trigeminal convergent neurons (77.9 +/- 4.4%; 72.5 +/- 4.6% and 78.5 +/- 3.6% inhibition, respectively) and these inhibitions were followed by long-lasting aftereffects. In addition, both the acupuncture- and noxious thermal stimulation-evoked inhibitions were significantly reduced by systemic naloxone (0.4 mg/kg, i.v.). Since the antinociceptive effects elicited by acupuncture (i) had a similar magnitude and time-course to those evoked by noxious thermal stimulation, (ii) exhibited a lack of topographical specificity and (iii) involved an opioidergic link, we would suggest that, at least in our experimental conditions, acupuncture manoeuvres trigger the neuronal mechanisms involved in diffuse noxious inhibitory controls.

Acupuncture Points↗

Diffuse noxious inhibitory controls in man. Involvement of the spinoreticular tract.

In normal subjects, heterotopic painful stimuli induce simultaneous and parallel decreases in the sensation of pain and in the spinal nociceptive flexion (RIII) reflex evoked by electrical stimulation of the sural nerve. This inhibition of the RIII reflex is not seen in tetraplegic patients with clinically complete spinal cord transection, suggesting that supraspinal structures are involved in this type of inhibition, mediated through 'Diffuse Noxious Inhibitory Controls' (DNIC). In the present study, the effects of heterotopic nociceptive stimuli on the RIII reflex were examined in 3 patients with unilateral thalamic vascular lesions and in 3 with Wallenberg's syndrome (WS). In the former, as in normal subjects, nociceptive electrical conditioning stimuli applied to the analgesic hand produced a profound inhibition of the RIII reflex followed by long-lasting after-effects. No inhibition was observed in the WS patients. The same conditioning procedure applied to the nonanalgesic hand of the WS patients resulted in inhibition and after-effects similar to those observed in normal subjects. The fact that noxious but nonpainful stimuli triggered DNIC in the patients with thalamic lesions excludes the possibility that masking of pain by a second painful focus is mainly due to attentional processes. It is also concluded that lemniscal and spinothalamic pathways are not involved in the triggering of DNIC in man and it is suggested that the brainstem and probably the spinoreticular tract are key neuronal links in the loop subserving DNIC in man.

Adult↗

Ascending pathways in the spinal cord involved in the activation of subnucleus reticularis dorsalis neurons in the medulla of the rat.

1. Recordings were made from neurons in the left medullary subnucleus reticularis dorsalis (SRD) of anesthetized rats. Two populations of neurons were recorded: neurons with total nociceptive convergence (TNC), which gave responses to A delta- and C-fiber activation from the entire body after percutaneous electrical stimulation, and neurons with partial nociceptive convergence (PNC), which responded to identical stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-fiber peak of activation from some, mainly contralateral, parts of the body. 2. The effects of various, acute, transverse sections of the cervical (C4-C5) spinal cord on the A delta- and C-fiber-evoked responses were investigated by building poststimulus histograms (PSHs) after 50 trials of supramaximal percutaneous electrical stimulation of the extremity of either hindpaw (2-ms duration; 3 times threshold for C-fiber responses), before and 30-40 min after making the spinal lesion. 3. In the case of TNC neurons, hemisections of the left cervical cord blocked the responses elicited from the right hindpaw and slightly, but not significantly, diminished those evoked from the left hindpaw. Conversely, hemisections of the right cervical cord abolished TNC responses elicited from the left hindpaw without significantly affecting the responses elicited from the right hindpaw. 4. Lesioning the dorsal columns or the left dorsolateral funiculus was found not to affect the TNC neuronal responses elicited from either hindpaw. By contrast, lesioning the left lateral funiculus or the most lateral part of the ventrolateral funiculus, respectively, reduced and blocked the responses elicited from the right hindpaw without affecting those evoked from the left hindpaw. 5. After lesions that included the most lateral parts of the left ventral funiculus, PNC neuronal responses elicited from the right hindpaw were also abolished, whereas those elicited from the left hindpaw remained unchanged. 6. We conclude that the signals responsible for the activation of SRD neurons travel principally in the lateral parts of the ventrolateral quadrant, a region that classically has been implicated in the transmission of noxious information. Both a crossed and a double-crossed pathway are involved in this process. The postsynaptic fibers of the dorsal columns and the spinocervical and spinomesencephalic tracts do not appear to convey signals that activate SRD neurons. 7. The findings also suggest that lamina I nociceptive specific neurons, the axons of which travel within the dorsolateral funiculus, do not contribute very much to the activation of SRD neurons.

Afferent Pathways↗

Convergence of heterotopic nociceptive information onto neurons of caudal medullary reticular formation in monkey (Macaca fascicularis).

1. Recordings were made in anesthetized monkeys from neurons in the medullary reticular formation (MRF) caudal to the obex. Responses of 19 MRF neurons to mechanical, thermal, and/or electrical stimulation were examined. MRF neurons exhibited convergence of nociceptive cutaneous inputs from widespread areas of the body and face. 2. MRF neurons exhibited low levels of background activity. Background activity increased after periods of intense cutaneous mechanical or thermal stimulation. Nearly all MRF neurons tested failed to respond to heterosensory stimuli (flashes, whistle sounds), and none responded to joint movements. 3. MRF neurons were excited by and encoded the intensity of noxious mechanical stimulation. Responses to stimuli on contralateral limbs were greater than those to stimuli on ipsilateral limbs. Responses were greater to stimuli on the forelimbs than to stimuli on the hindlimbs. 4. MRF neurons responded to noxious thermal stimulation (51 degrees C) of widespread areas of the body. Mean responses from stimulation at different locations were generally parallel to those for noxious mechanical stimulation. Responses increased with intensity of noxious thermal stimulation (45-50 degrees C). 5. MRF neurons responded with one or two peaks of activation to percutaneous electrical stimulation applied to the limbs, the face, or the tail. The differences in latency of responses to stimulating two locations along the tail suggested that activity was elicited by activation of peripheral fibers with a mean conduction velocity in the A delta range. Stimulation of the contralateral hindlimb elicited greater responses, with lower thresholds and shorter latencies, than did stimulation of the ipsilateral hindlimb. 6. Electrophysiological properties of monkey MRF neurons resembled those of neurons in the medullary subnucleus reticularis dorsalis (SRD) in the rat. Neurons in the caudal medullary reticular formation could play a role in processing nociceptive information. Convergence of nociceptive cutaneous input from widespread areas of the body suggests that MRF neurons may contribute to autonomic, affective, attentional, and/or sensory-motor processes related to pain.

Action Potentials↗

Studies of the brain structures involved in diffuse noxious inhibitory controls: the mesencephalon.

1. Diffuse noxious inhibitory controls (DNIC) were compared in control sham-operated rats and in rats with lesions of mesencephalic structures involved in the modulation of pain, namely the periaqueductal gray (PAG), cuneiformis nucleus (CNF), and parabrachial nucleus (PB). 2. Lesions were induced by ibotenic acid: 4 micrograms (0.2 microliter) injected bilaterally in the PAG or the CNF-PB area or 10 micrograms (0.5 microliter) injected unilaterally in the CNF or PB. Control animals were microinjected with the vehicle (artificial CSF) alone. Histological controls were performed at the end of each electrophysiological experiment. Only the animals in which the target structure (PAG, CNF, or PB) was completely destroyed in its entire rostrocaudal length were selected. With the exception of the cell bodies of the trigeminal mesencephalic nucleus, all neurons were destroyed in these regions. 3. At least 1 wk after the microinjection procedure, recordings were made from convergent neurons in both the right and left trigeminal nucleus caudalis. These neurons were activated by both noxious and nonnoxious stimuli applied to their excitatory receptive fields and gave responses due to activation of both A- and C-fibers after percutaneous electrical stimulation of their receptive fields. These types of response were inhibited by applying noxious conditioning stimuli to heterotopic areas of the body, namely immersing a paw in a 50 degrees C water bath. A virtually total block of the responses was observed during the application of the noxious conditioning stimulus, and this was followed by long-lasting poststimulus effects. 4. The general properties of neurons (sizes of receptive fields, spontaneous activity, thresholds to obtain C-fiber-evoked responses, responses to C-fiber activation) were all found to be similar in the control and the lesioned animals. The percentage inhibition of the C-fiber-evoked responses of the trigeminal convergent neurons elicited by the noxious conditioning stimuli were found to not be significantly different in any group of animals; in all the animals, inhibitions exceeded 85% during the immersion of either paw and were followed by long-lasting poststimulus effects. 5. We conclude that the PAG, CNF, and PB, three structures that are putatively involved in the modulation of pain, do not participate directly in the supraspinal part of the loop subserving DNIC. The involvement of other structure(s) and a possible indirect modulation of DNIC are discussed. It is also concluded that the PAG, CNF, and PB do not participate directly in the tonic descending inhibitory controls, which are presumed to modulate the activity of convergent neurons.

Anesthesia↗

[Diffuse noxious inhibitory controls: theoretical aspects applied to the effects of regional administration of morphine].

Assuming a relatively high background activity of convergent neurons, we have suggested that their pain-signalling message could consist in the contrast between the high rate of firing in the segmental neuronal pool induced by the painful focus and the D.N.I.C.-mediated silence of the remaining neuronal population. This notion is substantiated by several observations in the rat regarding morphine analgesia: a clear lifting of D.N.I.C. is observed following systemic (0.1-1 mg/kg; i.v.), intraventricular (0.6-2.5 micrograms) or intrathecal (15 micrograms) morphine. All these procedures could restore the initial level of background activity, analgesia resulting from the attenuation of the postulated contrast.

Animals↗

[Peripheral and spinal pathways involved in diffuse inhibitory controls induced by noxious stimulation. Neurosurgical approach in rats].

Electrophysiological recordings were made from spinal and trigeminal dorsal horn convergent neurones which allowed the investigation of some mechanisms underlying Diffuse Noxious Inhibitory Controls (D.N.I.C.) to be made. These controls are exclusively triggered by the activation of A delta and/or C peripheral fibres and involve a supraspinal loop. The ascending and descending parts of the looped pathway are confined within the anterolateral quadrants and the posterolateral funiculi respectively.

Animals↗

Effects of systemic morphine upon A delta- and C-fibre evoked activities of subnucleus reticularis dorsalis neurones in the rat medulla.

The effects of intravenous administration of morphine were examined on A delta- and C-fibre evoked activities of subnucleus reticularis dorsalis (SRD) neurones in the rat medulla. This region may have an important role in nociception since SRD neurones exhibit whole body receptive fields from which they can be activated preferentially or exclusively by noxious stimulation. The present study demonstrates that morphine can depress the C-fibre evoked responses of SRD neurones in a dose-related (3-12 mg/kg range) and naloxone reversible fashion; however the A delta-fibre evoked responses of these neurones were depressed only with the greatest dose employed. Since a similar dose can depress by 50% the C-fibre evoked activities of SRD and spinal dorsal horn convergent neurones, it is suggested that the depressant effect of morphine on SRD neurones arises primarily from its spinal action.

Animals↗

Segmental release of Met-enkephalin-like material from the spinal cord of rats, elicited by noxious thermal stimuli.

In order to investigate possible changes induced by noxious thermal stimuli in the activity of enkephalinergic neurones at various levels of the spinal cord, either the whole cord, the cervicotrigeminal area or the lumbar area were perifused with artificial CSF at a rate of 0.1 ml/min in halothane anaesthetized rats, and Met-enkephalin-like material (MELM) was measured in 0.5 ml fractions collected from the perifusates. Immersing the muzzle of intact rats in water at 52 degrees C produced a significant enhancement of MELM content in perifusates from both the whole spinal cord and the cervicotrigeminal area but not from the lumbar area. Heating the tail resulted in an increase in MELM release from the whole spinal cord of intact as well as of cervically transected rats. It is concluded that noxious thermal stimuli can induce a segmental release of MELM, i.e., only within spinal zones receiving the nociceptive inputs.

Animals↗

Encoding of electrical, thermal, and mechanical noxious stimuli by subnucleus reticularis dorsalis neurons in the rat medulla.

1. In anesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurons that exhibited convergence of nociceptive inputs from the entire body. Neurons with total nociceptive convergence (TNC) responded to suprathreshold percutaneous electrical stimuli (2-ms duration) with an early and a late peak due to activation of A delta- and C-fibers, respectively, no matter which part of the body was stimulated. Neurons with partial nociceptive convergence (PNC) responded to the same stimuli 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. The characteristics of the responses of these neurons to the application of graded intensities of electrical, thermal, and mechanical stimuli were analyzed. 2. All TNC neurons and 85% of PNC neurons responded to A delta- and C-fiber activation following percutaneous electrical stimulation of the contralateral hindpaw. With regard to A delta-fiber-evoked responses, a linear relationship between the logarithm of the applied current and the magnitude of the responses was found within the 0.25- to 6.0-mA and 0.5- to 24-mA ranges for TNC and PNC neurons, respectively; however, these curves were essentially similar. With regard to C-fiber-evoked responses, such a linear relationship was found within the 1.5- to 6.0-mA range for both types of SRD neurons, although the TNC neurons presented larger C-fiber-evoked responses than did the PNC neurons. 3. TNC and PNC neurons linearly increased their discharges during the application of noxious thermal stimuli to the contralateral hindpaw within the range 44-52 degrees C; the mean responses evoked by noxious heat from TNC neurons were of higher magnitude than those from PNC neurons. The majority of SRD neurons presented long-lasting afterdischarges, especially with the highest temperature employed (52 degrees C). 4. TNC neurons monotonically increased their discharges during graded mechanical or thermal stimulation of the tail. When mechanical stimuli were applied, a linear relationship was found between the logarithm of the strength of the mechanical stimulus and the neuronal discharges, in the 5.3- to 7.4-N/cm2 range. With thermal stimulation, TNC neurons linearly increased their discharges in the 44-52 degrees C range. When increasing amounts of the tail were immersed in a 50 degrees C waterbath, TNC neurons increased their discharges within a restricted range of tail surface areas (0.9-5.7 cm2); further increases in the stimulated surface size were not followed by increases in firing rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Encoding of nociceptive thermal stimuli by diffuse noxious inhibitory controls in humans.

1. It has previously been shown that, in normal humans, heterotopic painful thermal conditioning stimuli induce parallel increase in the thresholds of a spinal nociceptive flexion reflex (RIII reflex) and the concurrent sensation of pain elicited by electrical stimulation of the sural nerve. On the basis of analogous animal studies, we proposed that such phenomena could be related to diffuse noxious inhibitory controls (DNIC), which have been described in the rat. The present study, which was carried out on normal volunteer subjects, was particularly concerned with the extent and temporal characteristics of the depressive effects of DNIC triggered by painful thermal stimuli on RIII reflex activity. In addition, because it was possible that these depressive effects could have resulted from a direct postsynaptic inhibition of motoneurons, a second part of the study was aimed at determining whether or not the heterotopic noxious thermal stimuli also affected the excitability of alpha-motoneurons, as monitored by the monosynaptic Hoffmann reflex (H reflex) technique. 2. In the 11 subjects under study, application of moderate, nonnoxious temperatures (40-44 degree C) to the contralateral hand (via a thermoregulated and agitated waterbath) did not modify the RIII reflex nor the associated sensation of pain. By contrast noxious temperatures clearly depressed the RIII reflex and the concurrent sensation of pain, both during and after the conditioning procedure (CP), in a direct linear relationship to the temperature of the waterbath in the 45-47 degree C range; the maximal depressive effect was observed with the highest conditioning temperature. A significant relationship was also found between the extent of the RIII depression during the CP and that during a 10-min period of post-CP observation. 3. The depressive effects observed on both the RIII reflex and pain were not associated with clear change in autonomic functions. Respiration remained stable during the sessions, with no significant relationship between the temperatures of the waterbath and respiratory rate. Heart rate was slightly but significantly increased during the immersion of the hand in the 46 or 47 degree C waterbaths; this increase, however, ceased with the end of CP. 4. Application of thermal conditioning stimuli produced a slight but nonsignificant increase of the monosynaptic H reflex during the first minute of CP, no matter what was the temperature of the waterbath. However, there were no subsequent variations during the 6-min period of post-CP observation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Intracerebroventricular morphine restores the basic somesthetic activity of dorsal horn convergent neurones in the rat.

We have proposed that a painful focus will disturb the global activity of spinal and trigeminal convergent neurones in two complementary ways: by activation of the corresponding segmental pool of neurones and by an inhibition mediated by diffuse noxious inhibitory controls of the remaining neuronal population. Morphine (10 micrograms) administered within the third ventricle blocks diffuse noxious inhibitory controls acting on a basic somesthetic activity simulated by responses of convergent neurones to innocuous stimuli. It is proposed that analgesia induced by intracerebroventricular morphine could result, at least in part, from restoration of the basic somesthetic activity.

Animals↗