Abstract
Much evidence indicates that hypothalamus-derived neuropeptides, oxytocin, orexins A and B, inhibit nociceptive transmission in the rat spinal dorsal horn. In order to unveil cellular mechanisms for this antinociception, the effects of the neuropeptides on synaptic transmission were examined in spinal lamina II neurons that play a crucial role in antinociception produced by various analgesics by using the whole-cell patch-clamp technique and adult rat spinal cord slices. Oxytocin had no effect on glutamatergic excitatory transmission while producing a membrane depolarization, γ-aminobutyric acid (GABA)-ergic and glycinergic spontaneous inhibitory transmission enhancement. On the other hand, orexins A and B produced a membrane depolarization and/or a presynaptic spontaneous excitatory transmission enhancement. Like oxytocin, orexin A enhanced both GABAergic and glycinergic transmission, whereas orexin B facilitated glycinergic but not GABAergic transmission. These inhibitory transmission enhancements were due to action potential production. Oxytocin, orexins A and B activities were mediated by oxytocin, orexin-1 and orexin-2 receptors, respectively. This review article will mention cellular mechanisms for antinociception produced by oxytocin, orexins A and B, and discuss similarity and difference in antinociceptive mechanisms among the hypothalamic neuropeptides and other endogenous pain modulators (opioids, nociceptin, adenosine, adenosine 5’-triphosphate (ATP), noradrenaline, serotonin, dopamine, somatostatin, cannabinoids, galanin, substance P, bradykinin, neuropeptide Y and acetylcholine) exhibiting a change in membrane potential, excitatory or inhibitory transmission in the spinal lamina II neurons.
Highlights
Somatosensory information from the periphery to spinal cord is transmitted through the dorsal root to the dorsal horn whose gray matter is divided into six laminae named I–VI by Rexed [1]
In partial nerve injury rat models compared with sham rats, primary-afferent-evoked inhibitory transmission is inhibited in spinal lamina II neurons; γ-aminobutyric acid (GABA)-synthesizing enzyme expression is reduced in level in the spinal dorsal horn [10]
The present review article demonstrated that the antinociceptive effects of hypothalamic neuropeptides are produced by membrane depolarization and/or increased spontaneous release of L-glutamate from nerve terminals, both of which result in action potential production that leads to enhanced spontaneous inhibitory transmission by activating their specific receptors in the adult rat spinal lamina II
Summary
Somatosensory information from the periphery to spinal cord is transmitted through the dorsal root to the dorsal horn whose gray matter is divided into six laminae named I–VI by Rexed [1]. Hypothalamus-derived neuropeptides, oxytocin, orexins A and B, that have an ability to alleviate pain when intrathecally administrated, were shown to exhibit a similar synaptic modulation, i.e., inhibitory transmission facilitation following excitatory transmission facilitation, in adult rat spinal lamina II neurons [20,21,22] Their modulatory actions were either similar to or different from those of the other endogenous pain modulators (opioids, nociceptin, adenosine, adenosine 5’-triphosphate (ATP), noradrenaline, serotonin, dopamine, somatostatin, cannabinoids, galanin, substance P, bradykinin, neuropeptide Y and acetylcholine) in the spinal cord level. This review article will mention cellular mechanisms for synaptic modulation produced by oxytocin, orexins A and B and other endogenous pain modulators’ ones that are related to the present topics, and discuss a similarity and difference in antinociceptive mechanisms among these modulators
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