Neurohormonal effects of oxytocin and vasopressin receptor agonists on spinal pain processing in male rats
Abstract
Oxytocin (OT) and arginine vasopressin (AVP) are 2 neuropeptides that display well-known effects on the reproductive system. Although still controversial, oxytocin and vasopressin were demonstrated to exert potent effects on the nociceptive system when administered directly in various central nervous structures. On the other hand, little is known about their peripheral (hormonal) actions on nociception and pain responses. The aim of the present work was to characterize the effects of physiological blood concentrations of OT and AVP on spinal nociception and on pain responses. To do so, growing doses of OT or AVP were administered intravenously and the nociceptive processing by spinal cord neurons was analyzed in anesthetized male rats in vivo. We observed that the action potentials mediated by C-type nociceptive fibers was strongly reduced (antinociception) after intravenous injections of low doses of OT (<5 μg) or AVP (<500 pg), whereas an increase (pronociception) was observed at higher doses. Interestingly, antinociceptive and pronociceptive effects were fully abolished in the presence of the OT receptor antagonist and the AVP receptor antagonist type 1A (V1A), respectively. We confirmed this result with a behavioral model of forced swim stress-induced analgesia associated with plasmatic release of OT (and not vasopressin). Stress-induced analgesia was transiently lost after i.v. administration of OTR antagonist. Together, the present work provides straightforward evidence that blood levels of OT and AVP modulate nociception, windup plasticity and pain responses. The final target structures explaining these effects remains to be identified but are likely to be C-type nociceptors.
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One mechanism of oxytocin antinociception involves engagement of GABA-mediated inhibitory circuits at superficial layers of spinal cord dorsal horn neurones, which express oxytocin receptors and receive direct projections from hypothalamic oxytocin neurones, reducing Aδ/C-fibre afferent signalling and ascending nociceptive input.
“One mechanism involves the engagement of GABA‐mediated inhibitory circuits at the superficial layers of spinal cord dorsal horn neurones, which express oxytocin receptors 7 and receive direct projections from hypothalamic oxytocin neurones 8, 9, reducing Aδ/C‐fibre afferent signalling and ascending nociceptive input 10, 11, 12, 13, 14.”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [12]
Animal studies have shown that oxytocin can specifically reduce Aδ/C-fibre afferent signalling and ascending nociceptive input at the level of spinal cord dorsal horn neurones by engaging GABA-mediated inhibitory cellular mechanisms.
“animal studies have shown that oxytocin can specifically reduce Aδ/C‐fibre afferent signalling and ascending nociceptive input at the level of spinal cord dorsal horn neurones by engaging GABA‐mediated inhibitory cellular mechanisms 10, 11, 12, 13, 14, 29.”
From The Analgesic Effect of Oxytocin in Humans: A Double‐Blind, Placebo‐Controlled Cross‐Over Study Using Laser‐Evoked Potentials (2016) · cites this paper as [12]
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- Authors
- Juif, P.-E., & Poisbeau, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Poisbeau, Pierrick
- Venue
- Pain
- Published
- 2013-08
- Volume
- 154
- Issue
- 8
- Pages
- 1449-1456
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2155592901
- Cited by
- 101
- References
- 61
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 8 · 2023: 5 · 2022: 5 · 2021: 9 · 2020: 9 · 2019: 9 · 2018: 11 · 2017: 13 · 2016: 7 · 2015: 4 · 2014: 11 · 2013: 3
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Institut Universitaire de France
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- oxytocin, vasopressin, spinal nociception, antinociception, pronociception, stress-induced analgesia, oxytocin receptor antagonist
- MeSH terms
- Action Potentials, Analgesics, Animals, Arginine Vasopressin, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Interactions, Hyperalgesia, Male, Neurons, Oxytocin, Pain, Spinal Cord, Swimming, Rats, Sprague-Dawley, Pain Threshold, Receptors, Vasopressin, Nerve Fibers, Unmyelinated, Rats
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