Oxytocin inhibits the activity of acid‐sensing ion channels through the vasopressin, V1A receptor in primary sensory neurons
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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, V1A 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 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 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 V1A receptors.
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Both OT and AVP inhibit neuronal signaling in dorsal root ganglia, and these effects can be inhibited by a selective V1aR antagonist but not by an OTR antagonist.
“Although both OT and AVP inhibit neuronal signaling in dorsal root ganglia, these effects can be inhibited by a selective V1aR antagonist but not by an OTR antagonist.”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [41]
The analgesic effects of peripheral V1aR activation by OT and AVP may be mediated by V1aR modulation of ion channels in primary sensory neurons.
“These analgesic effects of peripheral activation of V1aRs by OT and AVP may be mediated by V1aR modulation of ion channels in primary sensory neurons [41; 42].”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [41]
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- Authors
- Qiu, F., Qiu, C., Cai, H., Liu, T., Qu, Z., Yang, Z., Li, J., Zhou, Q., & Hu, W.
- Affiliations
- Hubei University of Science and Technology (CN)
- Hubei University (CN)
- University of California, Irvine (US)
- Corresponding author
- Hu, Wang‐Ping
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2014-05-27
- Volume
- 171
- Issue
- 12
- Pages
- 3065-3076
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC4055206
- OpenAlex
- W1540241568
- Cited by
- 67
- References
- 74
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 9 · 2014: 2
- FWCI
- 5.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- oxytocin, acid-sensing ion channels, vasopressin V1a receptor, dorsal root ganglion neurons, primary sensory neurons, peripheral analgesia, acid-induced pain, nociception, vasopressin, acetic acid-induced writhing
- MeSH terms
- Action Potentials, Analgesics, Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Female, Ganglia, Spinal, Mice, Inbred C57BL, Oxytocin, Sensory Receptor Cells, Rats, Sprague-Dawley, Receptors, Vasopressin, Mice, Knockout, Acetic Acid, Nociception, Nociceptive Pain, Acid Sensing Ion Channels, Acid Sensing Ion Channel Blockers
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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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