Central CRH administration changes formalin pain responses in male and female rats

Corticotropin-releasing hormone (CRH) is suggested to be involved in the regulation of pain. To better evaluate the CRH-mediated behavioral alterations in the formalin inflammatory pain test, we administered CRH or the CRH receptor antagonist α-helical CRH9–41 (ahCRH) intracerebroventricularly to male and female rats and compared the effects with those of saline control. Nociceptive stimulation was carried out through a subcutaneous injection of dilute formalin (50 μL, 10%) in the plantar surface of the hind paw. In both sexes, formalin-induced responses, recorded for 60 min, were affected by CRH but not by ahCRH treatment. Paw flexing duration was decreased in both sexes during the formalin interphase period in the CRH-treated group compared to saline control groups; however, licking of the injected paw was markedly increased by the same treatment at other time periods. Treatments induced only a few changes in spontaneous non-pain behaviors, which do not account for the effects on pain response. In conclusion, these data demonstrate the ability of CRH to affect the behavioral responses to an inflammatory nociceptive stimulus, and that the effects can be in opposite directions depending on the behavioral response considered.

Research highlights
► CRH but not CRH antagonist, administered centrally, affects formalin induced pain responses.
► CRH-induced changes are different depending on the pain responses considered and sex.
► CRH-induced effects can increase or decrease pain