痛覚過敏に対するカルシトニンの抗侵害受容効果―卵巣摘出ラットの免疫組織化学的検討

Antinociceptive Effect of Calcitonin. : An Immunohistochemical Study in Ovariectomized Rats

　卵巣摘出ラットにおけるカルシトニンの抗侵害受容効果を免疫組織化学的に検討した．両側卵巣摘出後にカルシトニンまたは溶媒を反復投与した群（OVX-calcitonin群，OVX-vehicle群），卵巣摘出後にカルシトニン投与に加えセロトニン合成阻害薬（pcpa）を投与した群（OVX-calcitonin-pcpa群），偽手術後にカルシトニンまたは溶媒を投与した群（sham-calcitonin群，sham-vehicle群）の5群を設定した．モデル作成4週後より4週間の投薬を行った後にホルマリンテストを行い，第5腰髄のc-fosタンパク（c-Fos）陽性細胞数を比較した．カルシトニンは，OVX群とsham群の両群においてc-Fos産生を抑制した．Pcpaによりカルシトニンのc-Fos産生抑制効果は消失した．すなわち，カルシトニンは抗侵害受容効果を有し，その抗侵害受容効果にはセロトニン下行抑制系が関与している．

　We immunohistochemically studied the antinociceptive effects of calcitonin in ovariectomized (OVX) rats. OVX-calcitonin-treated (n＝5) and OVX-vehicle (n＝5) rats were ovariectomized and underwent repeated injections of calcitonin or vehicle for 4 weeks. At the end of treatment, the OVX-calcitonin-pcpa-group (n＝5) was given intraperitoneal injections of p-chlorophenylalanine, an inhibitor of serotonin biosynthesis. Sham-calcitonin (n＝5) and sham-vehicle (n＝5) groups underwent sham operations, and were treated. Two hours after formalin tests, tissue sections of the spinal cord (L5) were immunostained for c-Fos. The number of c-Fos-immunoreactive neurons in the spinal cord was counted and used for analysis. The number of c-Fos-immunoreactive neurons increased in OVX rats. After treatment with calcitonin, the number of c-Fos-immunoreactive neurons decreased in both OVX and sham rats. Pcpa inhibits calcitonin-induced reduction of c-Fos production. These results show that calcitonin has antinociceptive effect, and the central serotonergic system is involved in the antinociceptive properties of calcitonin.