Biomedical subjects

Marie José Freund-Mercier

Publications and source records attributed to Marie José Freund-Mercier.

4 recordsLinked to original sources

PubMed2006

Oxytocin and electrical stimulation of the paraventricular hypothalamic nucleus produce antinociceptive effects that are reversed by an oxytocin antagonist.

In recent years, oxytocin has been implicated in a wide diversity of functions. The role of oxytocin in analgesia and pain modulation represents an important new function of an endogenous system controlling sensorial information. The paraventricular (PV) nucleus of the hypothalamus is one of the most important sources of oxytocin, and it has a very well-defined projection to the spinal cord. The location of this PV spinal cord projection correlates well with oxytocin binding sites at the dorsal horn of the spinal cord. In this work, we used rats with a chronic (46 days) sciatic loose ligature, an electrical stimulating electrode, and an intrathecal cannula, which reached the L4-L5 levels of the spinal cord. We compared the oxytocin effects with electrical stimulation of the PV and observed a significant reduction of the withdrawal responses to mechanical and cold stimulation applied to the ipsilateral and contralateral hind paws. An oxytocin antagonist administered intrathecally blocked the PV effects. Naloxone was also intrathecally injected 2 min before the PV stimulation, and we also observed a significant reduction of the withdrawal responses; however, this reduction was less pronounced. Our results support the hypothesis that oxytocin is part of the descending inhibitory control mechanisms having an important antinociceptive action. We cannot exclude a minor opiate participation in the OT action.

Animals↗

PubMed2006

Paraventricular hypothalamic influences on spinal nociceptive processing.

Oxytocin properties have been studied in different experimental models in order to obtain evidence for its analgesic properties. The analgesic effect of an oxytocinergic pathway descending from the hypothalamus reaching the dorsal horn of the spinal cord has been studied. In anesthetized rats, we recorded single units at the L4-L5 spinal dorsal horn level and stimulated the peripheral receptive field. The evoked responses were classified according to their latencies in A-beta, A-delta, C fibers, and postdischarge. We used these responses to evaluate the effects of electrical stimulation of the paraventricular nucleus (PV) of the hypothalamus. We observed a selective blockage of A-delta and C fibers related to the duration of the train stimulus duration. Similar effects were observed when oxytocin (OT) was applied directly on the spinal cord. The effects of OT and of PV electrical stimulation were reversed in a dose-dependent manner by application of the specific OT antagonist (OTA). These effects were observed in cells with reduced wind-up and cells displaying a clear wind-up response to peripheral stimulation. Superficial and deeper cells in the dorsal spinal cord were involved. The recorded cells were marked by pontamine blue iontophoretic injection after each cell recording, and their histological locations were specified. In order to obtain a behavioral correlation, we used rats with a loose ligature of the sciatic nerve and a chronic intrathecal catheter reaching the L4-L5 spinal cord level. We tested the hyperalgesia and allodynia of these animals using von Frey filaments and the application of acetone to the hind paws. Our results show a significant reduction in the mechanical and thermal test after the administration of 15 microl of 10(-6) M OT. Our electrophysiological, pharmacological, and behavioral results point out a clear OT antialgesic effect. The results are discussed on the basis of a previous work showing an OT blockage of glutamate activation. The paraventricular hypothalamic descending OT pathway is proposed as an interesting mechanism producing analgesia.

Action Potentials↗

PubMed2005

Inflammatory pain upregulates spinal inhibition via endogenous neurosteroid production.

Inhibitory synaptic transmission in the dorsal horn (DH) of the spinal cord plays an important role in the modulation of nociceptive messages because pharmacological blockade of spinal GABAA receptors leads to thermal and mechanical pain symptoms. Here, we show that during the development of thermal hyperalgesia and mechanical allodynia associated with inflammatory pain, synaptic inhibition mediated by GABAA receptors in lamina II of the DH was in fact markedly increased. This phenomenon was accompanied by an upregulation of the endogenous production of 5alpha-reduced neurosteroids, which, at the spinal level, led to a prolongation of GABAA receptor-mediated synaptic currents and to the appearance of a mixed GABA/glycine cotransmission. This increased inhibition was correlated with a selective limitation of the inflammation-induced thermal hyperalgesia, whereas mechanical allodynia remained unaffected. Our results show that peripheral inflammation activates an endogenous neurosteroid-based antinociceptive control, which discriminates between thermal and mechanical hyperalgesia.

Animals↗

PubMed2003

Actions of oxytocin and interactions with glutamate on spontaneous and evoked dorsal spinal cord neuronal activities.

Among the numerous pain control mechanisms that have been proposed, those acting at the spinal cord have been broadly studied, but little is known about how neuropeptides originating in supraspinal structures may relate to pain and analgesic mechanisms. Oxytocin (OT), in addition to its well known hormonal action, produces neuronal effects in various regions of the central nervous system. Indeed, some parvocellular neurons in the hypothalamic paraventricular nucleus (PVN) are oxytocinergic and project to the caudal part of the brain and the spinal cord. Moreover, the rat spinal cord shows a good overlap between the oxytocinergic hypothalamo-spinal neuron projections and the distribution of OT binding sites. However, the physiological significance of these binding sites is largely unknown. Extracellular unit activity of spinal cord neurons was recorded at the T13-L1 levels in male rats anesthetized with halotane. Somatic stimulation was applied to the inner and outer thigh of the ipsilateral hindpaw, and glutamate (GLU) and OT were locally delivered by pressure using pipettes coupled to recording electrodes. Our results show that spinal cord neurons, mainly located in the dorsal horn, in the intermediolateral cell column (IML) and in the intermediomedial gray matter (IMM), respond to the application of OT (71.5%) with activation (48%) or inhibition (52%). In some cases, opposite OT effects were observed during simultaneous recordings of two cells, suggesting OT activation of an inhibitory interneuron followed by the inhibition of the second recorded neuron. Increases in neuronal firing rate produced by GLU could be blocked by prior OT application. Finally, OT could reduce or partially block the responses to tactile and nociceptive somatic stimulation. We found that spinal cord neurons are sensitive to OT indicating that OT binding sites are functionally active. OT effects suggest the activation of inhibitory interneurons acting on a second order projecting cells to modulate afferent tactile and nociceptive information.

Animals↗