Article

Paraventricular oxytocinergic hypothalamic prevention or interruption of long-term potentiation in dorsal horn nociceptive neurons: Electrophysiological and behavioral evidence

Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus UNAM-Juriquilla, Querétaro, Mexico.
Pain (Impact Factor: 5.64). 07/2009; 144(3):320-8. DOI: 10.1016/j.pain.2009.05.002
Source: PubMed

ABSTRACT Spinal long-term potentiation (LTP) elicited by noxious stimulation enhances the responsiveness of dorsal horn nociceptive neurons to their normal input, and may represent a key mechanism of central sensitization by which acute pain could turn into a chronic pain state. This study investigated the electrophysiological and behavioral consequences of the interactions between LTP and descending oxytocinergic antinociceptive mechanisms mediated by the hypothalamic paraventricular nucleus (PVN). PVN stimulation or intrathecal oxytocin (OT) reduced or prevented the ability of spinal LTP to facilitate selectively nociceptive-evoked responses of spinal wide dynamic range (WDR) neurons recorded in anesthetized rats. In a behavioral model developed to study the effects of spinal LTP on mechanical withdrawal thresholds in freely moving rats, the long-lasting LTP-mediated mechanical hyperalgesia was transiently interrupted or prevented by either PVN stimulation or intrathecal OT. LTP mediates long-lasting pain hypersensitivity that is strongly modulated by endogenous hypothalamic oxytocinergic descending controls.

0 Bookmarks
 · 
81 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to explore the effect of electroacupuncture (EA) applied in the Zusanli (ST36) and Sanyinjiao (SP6) points on the N1 component of the cord dorsum potential (CDP) evoked by electrical stimulation of the sural nerve (SU) in the rat. The experiments were performed in 44 Wistar rats (250-300 g) anesthetized with ketamine (100 mg/kg) and xylazine (2 mg/kg). A bilateral laminectomy was performed to expose the L3 to S2 segments of the spinal cord. The SU nerve was exposed and placed on pairs of hook electrodes for electrical stimulation. The N1-CDPs were recorded with three silver-ball electrodes located on the dorsal surface of the L5 to S1 segments. Ipsilateral high and low EA stimulation (100, 2 Hz, 6 mA, 30 min) induced a considerable reduction in the amplitude (45 ± 5.6, 41 ± 6.2 %) of the N1-CDP recorded at the L6 segmental level. Recovery of the N1-CDP amplitude occurred approximately 1-3 s after EA. Sectioning of the saphenous and superficial peroneal nerves reduced the depressing effect provoked by the EA stimulation (18.7 ± 1.3, 27 ± 3.8 %). Similarly, sectioning of the posterior and anterior tibial, deep peroneal and gastrocnemius nerves partially reduced the effect provoked by EA (11 ± 1.5, 9.8 ± 1.1, 12.6 ± 1.9 %). Intravenous picrotoxin (1 mg/kg) also reduced the action of low and high EA (23 ± 4.8, 27 ± 5.2 %). It is suggested that EA stimulation depresses non-painful sensory pathways through the activation of specific inhibitory pathways that receive modulatory actions from other sensory and muscle afferent inputs in the rat spinal cord.
    Experimental Brain Research 04/2014; 232(9). DOI:10.1007/s00221-014-3965-2 · 2.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The treatment of chronic pain arising from deep tissues is currently inadequate and there is need for new pharmacological agents to provide analgesia. The endogenous paracrine hormone/neurotransmitter oxytocin is intimately involved in the modulation of multiple physiological and psychological functions. Recent experiments have given clear evidence for a role of oxytocin in the modulation of nociception. The present article reviews the existent human and basic science data related to the direct and indirect effects of oxytocin on pain. Due to its analgesic, anxiolytic, antidepressant and other central nervous system effects, there is strong evidence that oxytocin and other drugs acting through the oxytocin receptor could act as multifunctional analgesics with unique therapeutic value.
    Current Pharmaceutical Design 10/2014; DOI:10.2174/1381612820666141027111843 · 3.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anatomic, physiologic, and behavioral studies in animals suggest that spinally released oxytocin should produce analgesia in humans and may also protect from chronic pain after injury. In this article, the authors report preclinical toxicity screening of oxytocin for intrathecal delivery. Intrathecal oxytocin, 11 μg (6 U) or vehicle, was injected intrathecally in 24 rats, followed by frequent behavioral assessment and histologic examination of spinal contents 2 or 14 days after injection. In three dogs, a range of intrathecal oxytocin doses (18 to 550 μg in 0.5 ml) was injected followed by physiologic, biochemical, and behavioral assessments. Ten dogs were then randomized to receive five daily injections of intrathecal oxytocin, 550 μg in 0.5 ml, or vehicle with similar assessments and, necropsy and histologic analysis were conducted 2 days later. In rats, intrathecal oxytocin resulted in transient scratching and itching behaviors, without other differences from vehicle. There was no behavioral, gross anatomic, or histologic evidence of neurotoxicity. Dose ranging in dogs suggested mild effects on motor tone, blood pressure, and heart rate at the 550 μg dose. Repeated boluses in dogs did not produce behavioral, biochemical, neurological, gross anatomic, or histologic evidence of neurotoxicity. Substances, including natural neurotransmitters, may be toxic when administered in pharmacologic doses in the spinal cord. This preclinical toxicity screen in two species suggests that bolus injections of oxytocin in concentrations up to 1,100 μg/ml are unlikely to cause neurotoxicity. The authors also support cautious clinical application of intrathecal oxytocin under regulatory supervision.
    Anesthesiology 01/2014; 120(4). DOI:10.1097/ALN.0000000000000148 · 6.17 Impact Factor