Experimental Study: Interleukin-31 Augments Morphine-Induced Antinociceptive Activity and Suppress Tolerance Development in Mice
Morphine-induced antinociception is partially reduced in interleukin-31 (IL-31) receptor A (IL-31RA)-deficient mice, indicating that IL-31RA is crucial for morphine-induced peripheral antinociception. Herein, we examined the combined effects of IL-31 and morphine on the antinociceptive activity and...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/22/16548 |
| _version_ | 1797458906370277376 |
|---|---|
| author | Iwao Arai Minoru Tsuji Saburo Saito Hiroshi Takeda |
| author_facet | Iwao Arai Minoru Tsuji Saburo Saito Hiroshi Takeda |
| author_sort | Iwao Arai |
| collection | DOAJ |
| description | Morphine-induced antinociception is partially reduced in interleukin-31 (IL-31) receptor A (IL-31RA)-deficient mice, indicating that IL-31RA is crucial for morphine-induced peripheral antinociception. Herein, we examined the combined effects of IL-31 and morphine on the antinociceptive activity and itch-associated scratching behavior (LLS) in mice and elucidated the regulatory mechanisms. A hot-plate test was used to assess antinociception. LLS was automatically detected and recorded via a computer. IL-31RA mRNA expression was assessed using real-time polymerase chain reaction. Repeated pre-treatment with IL-31 resulted in significant antinociceptive activity. Repeated administration of morphine decreased the morphine-induced antinociceptive activity, LLS counts, and regular dose and inhibited IL-31-induced LLS. These results suggested that the repeated administration of morphine depleted inter-neuronal IL-31RA levels, preventing morphine-induced antinociception. Therefore, IL-31 may be helpful as an adjunct analgesic to morphine. To explore the benefits of IL-31, its influence on morphine-induced antinociceptive tolerance in mice was examined. An IL-31 and morphine combination increased the analgesic action, which increased the expression of DRG neuronal IL-31RA, elucidating the site of peripheral antinociception of morphine. This site may induce exocytosis of IL-31RA in the sensory nervous system. Collectively, the suppressive effect of IL-31 on morphine-induced antinociceptive tolerance may result from IL-31RA supplementation in sensory nerves. |
| first_indexed | 2024-03-09T16:44:51Z |
| format | Article |
| id | doaj.art-4b082aeee6ba42809425f328d221345d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:44:51Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4b082aeee6ba42809425f328d221345d2023-11-24T14:48:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221654810.3390/ijms242216548Experimental Study: Interleukin-31 Augments Morphine-Induced Antinociceptive Activity and Suppress Tolerance Development in MiceIwao Arai0Minoru Tsuji1Saburo Saito2Hiroshi Takeda3Department of Pharmacology, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara 324-8510, JapanDepartment of Pharmacology, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara 324-8510, JapanDivision of Environmental Allergy, The Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Tokyo 105-8461, JapanDepartment of Pharmacology, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara 324-8510, JapanMorphine-induced antinociception is partially reduced in interleukin-31 (IL-31) receptor A (IL-31RA)-deficient mice, indicating that IL-31RA is crucial for morphine-induced peripheral antinociception. Herein, we examined the combined effects of IL-31 and morphine on the antinociceptive activity and itch-associated scratching behavior (LLS) in mice and elucidated the regulatory mechanisms. A hot-plate test was used to assess antinociception. LLS was automatically detected and recorded via a computer. IL-31RA mRNA expression was assessed using real-time polymerase chain reaction. Repeated pre-treatment with IL-31 resulted in significant antinociceptive activity. Repeated administration of morphine decreased the morphine-induced antinociceptive activity, LLS counts, and regular dose and inhibited IL-31-induced LLS. These results suggested that the repeated administration of morphine depleted inter-neuronal IL-31RA levels, preventing morphine-induced antinociception. Therefore, IL-31 may be helpful as an adjunct analgesic to morphine. To explore the benefits of IL-31, its influence on morphine-induced antinociceptive tolerance in mice was examined. An IL-31 and morphine combination increased the analgesic action, which increased the expression of DRG neuronal IL-31RA, elucidating the site of peripheral antinociception of morphine. This site may induce exocytosis of IL-31RA in the sensory nervous system. Collectively, the suppressive effect of IL-31 on morphine-induced antinociceptive tolerance may result from IL-31RA supplementation in sensory nerves.https://www.mdpi.com/1422-0067/24/22/16548analgesiaantinociceptioninterleukin-31 (IL-31)interleukin receptor A (IL-31RA)IL-31 receptor A-deficient (IL-31RAKI) miceitch |
| spellingShingle | Iwao Arai Minoru Tsuji Saburo Saito Hiroshi Takeda Experimental Study: Interleukin-31 Augments Morphine-Induced Antinociceptive Activity and Suppress Tolerance Development in Mice International Journal of Molecular Sciences analgesia antinociception interleukin-31 (IL-31) interleukin receptor A (IL-31RA) IL-31 receptor A-deficient (IL-31RAKI) mice itch |
| title | Experimental Study: Interleukin-31 Augments Morphine-Induced Antinociceptive Activity and Suppress Tolerance Development in Mice |
| title_full | Experimental Study: Interleukin-31 Augments Morphine-Induced Antinociceptive Activity and Suppress Tolerance Development in Mice |
| title_fullStr | Experimental Study: Interleukin-31 Augments Morphine-Induced Antinociceptive Activity and Suppress Tolerance Development in Mice |
| title_full_unstemmed | Experimental Study: Interleukin-31 Augments Morphine-Induced Antinociceptive Activity and Suppress Tolerance Development in Mice |
| title_short | Experimental Study: Interleukin-31 Augments Morphine-Induced Antinociceptive Activity and Suppress Tolerance Development in Mice |
| title_sort | experimental study interleukin 31 augments morphine induced antinociceptive activity and suppress tolerance development in mice |
| topic | analgesia antinociception interleukin-31 (IL-31) interleukin receptor A (IL-31RA) IL-31 receptor A-deficient (IL-31RAKI) mice itch |
| url | https://www.mdpi.com/1422-0067/24/22/16548 |
| work_keys_str_mv | AT iwaoarai experimentalstudyinterleukin31augmentsmorphineinducedantinociceptiveactivityandsuppresstolerancedevelopmentinmice AT minorutsuji experimentalstudyinterleukin31augmentsmorphineinducedantinociceptiveactivityandsuppresstolerancedevelopmentinmice AT saburosaito experimentalstudyinterleukin31augmentsmorphineinducedantinociceptiveactivityandsuppresstolerancedevelopmentinmice AT hiroshitakeda experimentalstudyinterleukin31augmentsmorphineinducedantinociceptiveactivityandsuppresstolerancedevelopmentinmice |