Peripheral effect of a kappa opioid receptor on nociception

The effect of sex hormones on orofacial pain modulation is poorly understood. Objectives: The aim of the study was to investigate the effect of hormonal changes as a result of pregnancy, as well as that of the kappa (k) opioid receptor antagonist on female rats' sensitivity to the temporomandibular joint (TMJ) formalin test. Methods: Initially, female rats at estrus and pregnant females on day 19 of pregnancy received a 50ml formalin (1.5%) injection (Sigma®) in the right TMJ. Then, the selective k-opioid receptor antagonist nor-Binaltorphimine (nor-BNI) (Sigma®), was co-administered with the formalin. Next, additional groups received the k (200mg) receptor antagonist or 0.9% NaCl 24 hours prior to the periarticular injection of formalin. Results: The pregnant females showed a reduction in nociceptive responses to the TMJ formalin test when compared with those at estrus. Co-administration of nor-BNI with formalin into the TMJ region had no significant effect. The pre-injection of selective k- opioid receptor antagonist, nor-BNI, significantly enhanced the nociceptive behavioral responses in pregnant females. When applied in the contralateral TMJ, nor-BNI did not affect the magnitude of the nociceptive response induced by formalin. Conclusions: 1) The increase of the sex hormone levels, as result of pregnancy, induces a reduction of nociceptive behavioral responses to the TMJ formalin test; 2) the peripheral kappa opioid receptor activation, by endogenous opioid agonists release, is involved in the antinociception to TMJ formalin test, induced by pregnancy.