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

Minoru Tsuji, Iwao Arai, Kazuya Miyagawa, Hiroko Miyagishi, Atsumi Saito, Kotaro Takeda, Hiroshi Takeda, Nobutake Akiyama, Saburo Saito

Research output: Contribution to journalArticle

Abstract

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 μg/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 μg/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.

Original languageEnglish
Pages (from-to)378-388
Number of pages11
JournalEuropean Journal of Pain (United Kingdom)
Volume23
Issue number2
DOIs
Publication statusPublished - 01-02-2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

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    Tsuji, M., Arai, I., Miyagawa, K., Miyagishi, H., Saito, A., Takeda, K., Takeda, H., Akiyama, N., & Saito, S. (2019). Involvement of interleukin-31 receptor A in morphine-induced itching and antinociception in mice. European Journal of Pain (United Kingdom), 23(2), 378-388. https://doi.org/10.1002/ejp.1312