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.
Subject(s)
Hyperalgesia/physiopathology , Long-Term Potentiation/physiology , Nociceptors/metabolism , Oxytocin/metabolism , Paraventricular Hypothalamic Nucleus/metabolism , Posterior Horn Cells/metabolism , Analgesia/methods , Analgesics/metabolism , Analgesics/pharmacology , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Disease Models, Animal , Efferent Pathways/metabolism , Efferent Pathways/physiology , Electric Stimulation Therapy/methods , Hyperalgesia/drug therapy , Injections, Spinal , Long-Term Potentiation/drug effects , Male , Nociceptors/drug effects , Oxytocin/pharmacology , Pain Measurement/drug effects , Pain Threshold/drug effects , Pain Threshold/physiology , Posterior Horn Cells/drug effects , Rats , Rats, Wistar , Spinothalamic Tracts/drug effects , Spinothalamic Tracts/physiologyABSTRACT
Previously, we demonstrated that stimulation of the paraventricular hypothalamic nucleus diminishes the nociceptive dorsal horn neuronal responses, and this decrease was mediated by oxytocin in the rat. In addition, we have proposed that oxytocin indirectly inhibits sensory transmission in dorsal horn neurons by exciting spinal inhibitory GABAergic interneurons. The main purpose of the present study was to identify which of the neurons projecting to supraspinal structures to transmit somatic information are modulated by the hypothalamic-spinal descending activation. In anaesthetized rats, single-unit extracellular and juxtacellular recordings were made from dorsal horn lumbar segments, which receive afferent input from the toe and hind-paw regions. The projecting spinothalamic tract and postsynaptic dorsal column system were identified antidromically. Additionally, in order to label the projecting dorsal horn neurons, we injected fluorescent retrograde neuronal tracers into the ipsilateral gracilis nucleus and contralateral ventroposterolateral thalamic nucleus. Hence, juxtacellular recordings were made to iontophoretically label the recorded neurons with a fluorescent dye and identify the recorded projecting cells. We found that only nociceptive evoked responses in spinothalamic tract and postsynaptic dorsal column neurons were significantly inhibited (48.1 +/- 4.6 and 47.7 +/- 8.2%, respectively) and non-nociceptive responses were not affected by paraventricular hypothalamic nucleus stimulation. We conclude that the hypothalamic-spinal system selectively affects the transmission of nociceptive information of projecting spinal cord cells.