Central administration of oxytocin reduces hyperalgesia in mice: implication for cannabinoid and opioid systems.

Abstract

The neuropeptide oxytocin (OXT) contributes to the regulation of diverse cognitive and physiological functions including nociception. Indeed, OXT has been reported to be analgesic when administered directly into the brain, the spinal cord, or systemically. Although many authors have reported the analgesic effects of OXT, its mechanism has not been well elucidated. Recently, it has been also hypothesize that OXT, increasing intracellular concentration of calcium, could regulate the production of mediators, like endocannabinoids (eCB). It has been well documented that eCB are able to suppress pain pathways. The present study investigates the effect of OXT in paw carrageenan-induced pain. Intracerebroventricular (icv) administration of OXT, but neither intraperitoneal nor intraplantar route, induces an antihyperalgesic effect increasing paw withdrawal latency to mechanical or thermal stimuli. Our results clearly demonstrate that 3 and 6h following carrageenan challenge, central administration of OXT (30 ng/mouse) shows a significant antihyperalgesic activity. Moreover, for the first time, we demonstrate that CB1 receptor plays a key role in the antihyperalgesic effect of OXT. In fact our results show CB1 antagonist, but not the specific CB2 antagonist reduce OXT-induced antihyperalgesic effect. In addition, our data show that central OXT administration is able to reduce carrageenan-induced hyperalgesia but does not modify carrageenan-induced paw edema. Finally, using opioid antagonists we confirm an important role of opioid receptors. In conclusion, our experiments suggest that central administration of OXT reduces hyperalgesia induced by intraplantar injection of carrageenan, and this effect may work via cannabinoid and opioid systems.

• Authors: R Russo, G D'Agostino, G Mattace Raso, C Avagliano, C Cristiano, R Meli, A Calignano
• Journal: Peptides (Peptides) Vol. 38 Issue 1 Pg. 81-8 (Nov 2012) ISSN: 1873-5169 [Electronic] United States
• PMID: 22917880 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Analgesics, Non-Narcotic
• Narcotic Antagonists
• OXTR protein, mouse
• Receptor, Cannabinoid, CB1
• Receptor, Cannabinoid, CB2
• Receptors, Opioid
• Receptors, Oxytocin
• Naloxone
• Oxytocin
• Carrageenan
• Nitric Oxide Synthase Type I
• Nitric Oxide Synthase Type II
• Nos1 protein, mouse
• Nos2 protein, mouse
• Ptgs2 protein, mouse
• Cyclooxygenase 2

Topics

• Analgesics, Non-Narcotic (pharmacology)
• Animals
• Carrageenan (adverse effects)
• Cyclooxygenase 2 (metabolism)
• Dose-Response Relationship, Drug
• Edema (chemically induced, drug therapy)
• Hyperalgesia (chemically induced, drug therapy)
• Injections, Intraventricular
• Male
• Mice
• Motor Activity (drug effects)
• Naloxone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Nitric Oxide Synthase Type I (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Oxytocin (administration & dosage, pharmacology)
• Pain (chemically induced)
• Receptor, Cannabinoid, CB1 (antagonists & inhibitors, metabolism)
• Receptor, Cannabinoid, CB2 (antagonists & inhibitors, metabolism)
• Receptors, Opioid (metabolism)
• Receptors, Oxytocin (metabolism)
• Spinal Cord (drug effects, enzymology)