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Oxytocin inhibits the activity of acid‐sensing ion channels through the vasopressin, V 1A receptor in primary sensory neurons
Author(s) -
Qiu Fang,
Qiu ChunYu,
Cai Huilan,
Liu TingTing,
Qu ZuWei,
Yang Zhifan,
Li JiaDa,
Zhou QunYong,
Hu WangPing
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12635
Subject(s) - acid sensing ion channel , vasopressin , dorsal root ganglion , nociception , receptor , oxytocin , neuroscience , pharmacology , receptor antagonist , endocrinology , chemistry , medicine , antagonist , sensory system , ion channel , biology
Background and Purpose A 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 Approach Electrophysiological experiments were performed on neurons from rat DRG . Nociceptive behaviour was induced by acetic acid in rats and mice lacking vasopressin, V 1A receptors. Key Results OT 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 V 1A receptor antagonist SR 49059, 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 V 1A receptor knockout mice. Conclusions and Implications These results reveal a novel peripheral mechanism for the analgesic effect of OT involving the modulation of native ASICs in primary sensory neurons mediated by V 1A receptors.