Involvement of interleukin-31 receptor A in morphine-induced itching and antinociception in mice

Background Morphine is an effective analgesic for the treatment of severe pain, but it can cause itching in patients. In the present study, we examined the possible involvement of interleukin-31 (IL-31) receptor A (IL-31RA) on the morphine-induced itching and antinociception in mice. Methods Long-lasting scratching (LLS) and short-lasting scratching (SLS) were estimated as an indicator of itching and nonspecific behaviour, respectively, and antinociception was evaluated using a hot-plate test in mice. Results Morphine (5 mg/kg, s.c.) induced multiple episodes of SLS, few episodes of LLS, and antinociception in naive mice, with a close correlation observed between SLS or LLS counts and antinociception. In IL-31RA-deficient (IL-31RA(-/-)) mice, morphine (5 mg/kg, s.c.)-induced LLS but not SLS was completely abolished, while antinociception was partially suppressed with 2.5 and 5 mg/kg but not 10 mg/kg, s.c. of morphine administration. Interestingly, intracerebroventricular (i.c.v.) administration of morphine (10 mu g/mouse) significantly increased SLS but not LLS, and this effect was higher in IL-31RA(-/-) mice than that in wild-type mice. Furthermore, following i.c.v. administration of morphine (10 mu g/mouse), the antinociceptive effect was also significantly higher in IL-31RA(-/-) mice than that in wild-type mice. Conclusion Taken together, the present findings suggest that IL-31RA may play a significant role, perhaps in the sensory neurons and/or spinal cord rather than in the brain, in the modulation of morphine-induced itching and antinociception. Significance Here, we demonstrate a possible common mediator of itching and antinociception of morphine, interleukin-31 (IL-31) receptor A (IL-31RA). IL-31RA may be a noteworthy target for considering the novel mechanism of itch and pain signalling affected by morphine.