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Cellular Mechanisms for Antinociception Produced by Oxytocin and Orexins in the Rat Spinal Lamina II—Comparison with Those of Other Endogenous Pain Modulators

Department of Physiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan
Pharmaceuticals 2019, 12(3), 136; https://doi.org/10.3390/ph12030136
Received: 17 May 2019 / Revised: 31 August 2019 / Accepted: 12 September 2019 / Published: 16 September 2019
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. View Full-Text
Keywords: oxytocin; orexin A; orexin B; spinal dorsal horn; synaptic transmission; depolarization; antinociception; patch clamp; rat oxytocin; orexin A; orexin B; spinal dorsal horn; synaptic transmission; depolarization; antinociception; patch clamp; rat
MDPI and ACS Style

Kumamoto, E. Cellular Mechanisms for Antinociception Produced by Oxytocin and Orexins in the Rat Spinal Lamina II—Comparison with Those of Other Endogenous Pain Modulators. Pharmaceuticals 2019, 12, 136.

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