title: Involvement of TRPM2 in a wide range of inflammatory and neuropathic pain mouse models.
abstract: Recent evidence suggests a role of transient receptor potential melastatin 2 (TRPM2) in immune and inflammatory responses. We previously reported that TRPM2 deficiency attenuated inflammatory and neuropathic pain in some pain mouse models, including formalin- or carrageenan-induced inflammatory pain, and peripheral nerve injury-induced neuropathic pain models, while it had no effect on the basal mechanical and thermal nociceptive sensitivities. In this study, we further explored the involvement of TRPM2 in various pain models using TRPM2-knockout mice. There were no differences in the chemonociceptive behaviors evoked by intraplantar injection of capsaicin or hydrogen peroxide between wildtype and TRPM2-knockout mice, while acetic acid-induced writhing behavior was significantly attenuated in TRPM2-knockout mice. In the postoperative incisional pain model, no difference in mechanical allodynia was observed between the two genotypes. By contrast, mechanical allodynia in the monosodium iodoacetate-induced osteoarthritis pain model and the experimental autoimmune encephalomyelitis model were significantly attenuated in TRPM2-knockout mice. Furthermore, mechanical allodynia in paclitaxel-induced peripheral neuropathy and streptozotocin-induced painful diabetic neuropathy models were significantly attenuated in TRPM2-knockout mice. Taken together, these results suggest that TRPM2 plays roles in a wide range of pathological pain models based on peripheral and central neuroinflammation, rather than physiological nociceptive pain.
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: So
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Haraguchi
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Asakura
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Isami
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sakimoto
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Shirakawa
authors.affiliation: Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura Campus, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan; Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Electronic address: tknakaga@kuhp.kyoto-u.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000235:genetics*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000235:genetics*; D050053:TRPM Cation Channels / Q000172:deficiency / Q000502:physiology*
chemical_list: D050053:TRPM Cation Channels; C544443:TRPM2 protein, mouse
keywords: Inflammatory pain; Knockout mice; Neuropathic pain; Pain models; TRPM2