title: 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.
authors.affiliation: Centre National de la Recherche Scientifique and University of Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Research Group "Molecular Determinants of Pain", Strasbourg, France.
authors.forename: Pierre-Eric
authors.initials: PE
authors.lastname: Juif
authors.forename: Pierrick
authors.initials: P
authors.lastname: Poisbeau
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D010121:Oxytocin / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy / Q000473:pathology*; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000819:agonists; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013550:Swimming / Q000523:psychology
chemical_list: D000700:Analgesics; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; C033683:oxytocin, tri-Gly-; C107065:argipressin, Gly(OH9)-; D010121:Oxytocin