• Fang Qiu, Chun-Yu Qiu, Huilan Cai, Ting-Ting Liu, Zu-Wei Qu, Zhifan Yang, Jia-Da Li, Qun-Yong Zhou, and Wang-Ping Hu.
• Department of Pharmacology, Hubei University of Science and Technology, Xianning, China; College of Life Sciences, Hubei University, Wuhan, China.
• Br. J. Pharmacol. 2014 Jun 1;171(12):3065-76.

Background And PurposeA growing number of studies have demonstrated that oxytocin (OT) plays an analgesic role in modulation of nociception and pain. Most work to date has focused on the central mechanisms of OT analgesia, but little is known about whether peripheral mechanisms are also involved. Acid-sensing ion channels (ASICs) are distributed in peripheral sensory neurons and participate in nociception. Here, we investigated the effects of OT on the activity of ASICs in dorsal root ganglion (DRG) neurons.Experimental ApproachElectrophysiological experiments were performed on neurons from rat DRG. Nociceptive behaviour was induced by acetic acid in rats and mice lacking vasopressin, V1A receptors.Key ResultsOT inhibited the functional activity of native ASICs. Firstly, OT dose-dependently decreased the amplitude of ASIC currents in DRG neurons. Secondly, OT inhibition of ASIC currents was mimicked by arginine vasopressin (AVP) and completely blocked by the V1A receptor antagonist SR49059, but not by the OT receptor antagonist L-368899. Thirdly, OT altered acidosis-evoked membrane excitability of DRG neurons and significantly decreased the amplitude of the depolarization and number of action potentials induced by acid stimuli. Finally, peripherally administered OT or AVP inhibited nociceptive responses to intraplantar injection of acetic acid in rats. Both OT and AVP also induced an analgesic effect on acidosis-evoked pain in wild-type mice, but not in V1A receptor knockout mice.Conclusions And ImplicationsThese results reveal a novel peripheral mechanism for the analgesic effect of OT involving the modulation of native ASICs in primary sensory neurons mediated by V1A receptors.© 2014 The British Pharmacological Society.

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