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

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Interleukin Receptors
Pruritus
Morphine
Pain
Sensory Receptor Cells
Analgesics
Spinal Cord

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Tsuji, Minoru ; Arai, Iwao ; Miyagawa, Kazuya ; Miyagishi, Hiroko ; Saito, Atsumi ; Takeda, Kotaro ; Takeda, Hiroshi ; Akiyama, Nobutake ; Saito, Saburo. / Involvement of interleukin-31 receptor A in morphine-induced itching and antinociception in mice. In: European Journal of Pain (United Kingdom). 2019 ; Vol. 23, No. 2. pp. 378-388.
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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.",
author = "Minoru Tsuji and Iwao Arai and Kazuya Miyagawa and Hiroko Miyagishi and Atsumi Saito and Kotaro Takeda and Hiroshi Takeda and Nobutake Akiyama and Saburo Saito",
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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), vol. 23, no. 2, pp. 378-388. https://doi.org/10.1002/ejp.1312

Involvement of interleukin-31 receptor A in morphine-induced itching and antinociception in mice. / Tsuji, Minoru; Arai, Iwao; Miyagawa, Kazuya; Miyagishi, Hiroko; Saito, Atsumi; Takeda, Kotaro; Takeda, Hiroshi; Akiyama, Nobutake; Saito, Saburo.

In: European Journal of Pain (United Kingdom), Vol. 23, No. 2, 01.02.2019, p. 378-388.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Involvement of interleukin-31 receptor A in morphine-induced itching and antinociception in mice

AU - Tsuji, Minoru

AU - Arai, Iwao

AU - Miyagawa, Kazuya

AU - Miyagishi, Hiroko

AU - Saito, Atsumi

AU - Takeda, Kotaro

AU - Takeda, Hiroshi

AU - Akiyama, Nobutake

AU - Saito, Saburo

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

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