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

R. Russo, G. D'Agostino, G. Mattace Raso, C. Avagliano, C. Cristiano, R. Meli, A. Calignano

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)81-88
Number of pages8
Issue number1
Publication statusPublished - Nov 2012


  • analgesics, non-narcotic
  • animals
  • carrageenan
  • cyclooxygenase 2
  • dose-response relationship, drug
  • edema
  • hyperalgesia
  • injections, intraventricular
  • male
  • mice
  • motor activity
  • naloxone
  • narcotic antagonists
  • nitric oxide synthase type I
  • nitric oxide synthase type II
  • oxytocin
  • pain
  • receptor, cannabinoid, CB1
  • receptor, cannabinoid, CB2
  • receptors, opioid
  • receptors, oxytocin
  • spinal cord


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