Biomedical subjects

Miguel Condés-Lara

Publications and source records attributed to Miguel Condés-Lara.

9 recordsLinked to original sources

PubMed2006

GABA-mediated oxytocinergic inhibition in dorsal horn neurons by hypothalamic paraventricular nucleus stimulation.

In anaesthetized rats, we tested whether the unit activity of dorsal horn neurons that receive nociceptive input is modulated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN). An electrophysiological mapping of dorsal horn neurons at L3-L4 let us choose cells responding to a receptive field located in the toes region of the left hindpaw. Dorsal horn neurons were classified according to their response properties to peripheral stimulation. Wide Dynamic Range (WDR) cells responding to electrical stimulation of the peripheral receptive field and presenting synaptic input of Adelta, Abeta, and C-fibers were studied. Suspected interneurons that are typically silent and lack peripheral receptive field responses were also analyzed. PVN electrical stimulation inhibits Adelta (-55.0+/-10.2%), C-fiber (-73.1+/-6.7%), and post-discharge (-75.0+/-8.9%) peripheral activation in WDR cells, and silent interneurons were activated. So, this last type of interneuron was called a PVN-ON cell. In WDR cells, the inhibition of peripheral responses caused by PVN stimulation was blocked by intrathecal administration of a specific oxytocin antagonist or bicuculline. However, PVN-ON cell activation was blocked by the same specific oxytocin antagonist, but not by bicuculline. Our results suggest that PVN stimulation inhibits nociceptive peripheral-evoked responses in WDR neurons by a descending oxytocinergic pathway mediated by GABAergic PVN-ON cells. We discuss our observation that the PVN electrical stimulation selectively inhibits Adelta and C-fiber activity without affecting Abeta fibers. We conclude that Adelta and C-fibers receive a presynaptic inhibition mediated by GABA.

Action Potentials↗

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

Oxytocin actions on afferent evoked spinal cord neuronal activities in neuropathic but not in normal rats.

A hypothalamic oxytocinergic-descending pathway that reaches the dorsal horn of the spinal cord has been well documented and recently related to states of pain and analgesia. In order to study the action of the neuropeptide oxytocin (OT) on pain-related responses, we compared dorsal horn neuronal responses to electrical and mechanical stimulation of receptive fields in normal and neuropathic rats. Spinal nerve (L5 and L6) ligation (Chung rats) was used to produce experimental neuropathy. Single unit activity was recorded at the L4-L5 level from neurons identified as wide dynamic range presenting latency responses corresponding to A-beta, A-delta, C fibers and also exhibiting post-discharge, and wind-up. We tested intrathecally applied doses of 0.05, 0.1, 1, 2, 5, 10 I.U. of OT. Minor effects on responses to electrical stimulation were present in normal rats. Mechanical responses evoked by von Frey filaments were slightly reduced in normal animals. In neuropathic rats a dose of 1 I.U. produced a significant reduction in C-fibers and post-discharge activities, and doses of 2 I.U. caused a further, pronounced reduction in post-discharge, wind-up, and input values. However, the most marked change was the post-discharge reduction at 10 and 20 min after OT administration. Mechanical responses were significantly reduced in terms of their discharge rate response in neuropathic rats. The contrasting results obtained in normal and neuropathic rats revealed an important distinction between these animals and indicate that plastic changes occur as a consequence of nerve damage. In neuropathic rats, mechanisms involving ascending noxious information to the paraventricular nuclei and descending OT activities could be altered so sensitizing the OT receptors of the spinal dorsal horn cells and could explain our observations. Our results point out an anti-algesic OT effect in neuropathic rats.

Action Potentials↗

PubMed2004

Interamygdaloid connection of basolateral nucleus through the anterior commissure in the rat.

Basolateral amygdaloid nucleus interconnections through the anterior commissure (ac) are well visualized using wheat germ agglutinin-horseradish peroxidase tracer (WGA-HRP) in control animals. On the other hand, few neurons in the contralateral basolateral amygdaloid nucleus were labeled when the WGA-HRP was injected after a complete transection of the anterior commissure. These results indicate that the basolateral nucleus projects through the anterior commissure to the homologous amygdaloid nucleus in the contralateral hemisphere.

Amygdala↗

PubMed2003

Electrophysiological responses of interfascicular neurons of the rat anterior commissure to activation from the anterior olfactory nucleus, medial frontal cortex, and posterior nucleus of the amygdala.

Interfascicular neurons (IFNs) of the anterior commissure (AC) include short-axon and projection types which receive inputs from commissural collaterals. Therefore, it was proposed that IFNs may play a role in processing nerve impulses arising from the forebrain and delivered by these collaterals [Brain Res. 931 (2002) 81-91]. To determine possible inputs from the forebrain to IFNs we performed extracellular recordings of 25 neurons from anesthetized adult rats. Short-latency evoked potentials in IFNs were elicited by electrical stimulation of the anterior olfactory, posterior amygdaloid nuclei (PA), and medial frontal cortex. The IFN responses showed three distinct patterns, namely, a single action potential (AP) followed by what appear to be spontaneous discharge; a burst of high-frequency APs, and a single AP followed by a period devoid of APs. The latter response which was elicited by stimulation of the PA, may be explained by an intervening inhibitory interneuron, perhaps GABAergic in nature. Finally, IFNs seem not to project back to any of these three forebrain areas, as we failed to demonstrate antidromic activation.

Action Potentials↗

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↗

PubMed2002

Electrophysiological evidence that a set of interfascicular cells of the rat anterior commissure are neurons.

In mammals, the anterior commissure (AC) provides a route that interconnects homonymous areas of the basal forebrain. Recently, we reported the presence of short-axon and projection neurons among the axonal fascicles of the rat AC (i.e. interfascicular neurons; IFNs). This, coupled with the commissural inputs to these neurons, suggests that in addition to conveying nerve impulses, the AC may be a site of neural processing. To test this hypothesis, the electrophysiological activity of IFNs was recorded in adult albino rats. From extracellular recordings performed in 11 IFNs, it was found that these cells: (1), have a spontaneous discharge of a relatively low frequency (i.e. 0.04 +/- 0.1 to 5.9 +/- 3.2 spikes per second); (2), application of anodic current in the adjacent commissural fibers decreased this frequency; and (3), application of cathodic current increased the number of action potentials. Since observations made in Golgi-impregnated sections suggest that the main input to IFNs arises from their commissural collaterals, it is concluded that these cells may participate in the integration of interhemispheric nerve impulses.

Animals↗

PubMed1988

Suppression of noxious thermal evoked responses in thalamic central lateral nucleus by cortical spreading depression.

Several thalamic nuclei are associated with the processing of pain information and are influenced by cortical actions. This paper demonstrates a cortical influence upon the medial thalamic nuclei unit activity evoked by thermal noxious stimulation in rats. We studied the effects of cortical spreading depression (CSD) upon the responses of the centralis lateralis (CL) nucleus of the medial thalamus to noxious heat stimulation. Urethane was used as anaesthetic. Cells responding to noxious stimulation were localized in the dorsal portion of the CL. These cells responded like polymodal or nociceptive specific units in the spinal cord and exhibited their highest discharge frequency with noxious stimuli. When CSD is propagated and affects the medial frontal cortex it blocks the responses evoked in CL cells by noxious stimulation. Cortical cells located at this level also exhibited responses evoked by noxious stimulation. Our results suggest a cortical facilitatory control upon the noxious responses recorded in the CL cells.

Animals↗