臨床整形外科41巻3号

2006年03月発行

整形外科／基礎

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

著者： 高山文治¹ 菊地臣一¹ 紺野愼一¹ 関口美穂¹

所属機関： ¹福島県立医科大学医学部整形外科

ページ範囲：P.223 - P.230

　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．

参考文献

1）Albright F：Osteoporosis. Ann Intern Med 27：861-882, 1947

2）Buritova J, Honore P, Besson JM：Ketoprofen produces profound inhibition of spinal c-fos protein expression resulting from an inflammatory stimulus but not from noxious heart. Pain 67：379-389, 1996

3）Carrive P, Meyer-Carrive I：Changes in formalin-evoked spinal Fos expression and nociceptive behavior after oral administration of bufferin A（aspirin）and L-5409709（ibuprofen＋caffeine＋paracetamol）. Pain 70：253-266, 1997

4）Dubuisson D, Dennis SG：The formalin test：a quantitative study of the analgesic effects of morphine, meperidine, and brain stimulation in rats and cats. Pain 4：161-174, 1977

5）Gobelet C, Waldburger M, Meier JL：The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. Pain 48：171-175, 1992

6）Hamba M, Muro M, Hiraide T, et al：Expression of c-fos like protein in the rat brain after injection of interleukin-1-beta into the gingiva. Brain Res Bull 34：61-68, 1994

7）Hunt SP, Pini A, Evan G：Induction of c-fos like protein in spinal cord neurons following sensory stimulation. Nature 328：632-634, 1987

8）Ito A, Kumamoto E, Takeda M, et al：Mechanisms for ovariectomy-induced hyperalgesia and its relief by calcitonin：Participation of 5 HT1A-like receptor on C-afferent terminals in substantia geratinoza of the rat spinal cord. J Neurosci 20：6302-6308, 2000

9）Knopp JA, Diner BM, Blitz M, et al：Calcitonin for treating acute pain of osteoporotic vertebral compression fractures：a systematic review of randomized, controlled trials. Osteoporos Int Oct 16（10）：1281-1291, 2005, Epub Dec 22, 2004

10）Lima D, Avelino A, Coimbra A：Differential activation of c-fos in spinal neurons by distinct classes of noxious stimuli. Neuroreport 4：747-750, 1993

11）Lyritis GP, Ioannidis GV, Karachalios T, et al：Analgesic effect of salmon calcitonin suppositories in patients with acute pain due to recent osteoporotic vertebral crush fractures：a prospective double-blind, randomized, placebo-controlled clinical study. Clin J Pain 15：284-289, 1999

12）Menetrey D, Gannon A, Levine JD, et al：Expression of c-fos protein in interneurons and projection neurons of the spinal cord in response to noxious somatic, articular, and visceral stimulation. J Comp Neurol 285：177-195, 1989

13）Molander C, Xu Q, Grant G：The cytoarchitectonic organization of the spinal cord in the rat：the lower thoratic and lumbosacral cord. J Comp Neurol 230：133-141, 1984

14）Morgan JI, Curran T：Stimulus transcription coupling in the nervous system：Involvement of the inducible proto-oncogenes fos and jun. Trends Neurosci 12：459-462, 1989

15）Naranjo JR, Mellstörm B, Achaval M, et al：Molecular pathways of pain：Fos/Jun-mediated activation of a noncanonical AP-1 site in the predynorphim gene. Neuron 6：607-617, 1991

16）Presley RW, Menetrey D, Levine JD, et al：Systemic morphine suppresses noxious stimulus evoked Fos protein-like immunoreactivity in the rat spinal cord. J Neurosci 10：323-335, 1990

17）Roth A, Kolaric K：Analgetic activity of calcitonin in patients with painful osteolytic metastases of breast cancer. Results of a controlled randomized study. Oncology 43：283-287, 1986

18）Sanchez R, Nguyan D, Rocha W, et al：Diversity in the mechanisms of gene regulation by estrogen receptors. Bioassays 24：244-254, 2002

19）佐々木伸久，菊地臣一，紺野慎一・他：ラット椎間板ヘルニアモデルに対する各種NSAIDsの鎮痛効果．c-Fosによる検討．臨整外39：147-154, 2004

20）Shibata K, Takeda M, Ito A, et al：Ovariectomy-induced hyperalgesia and antinociceptive effect of elcatonin, a synthetic eel calcitonin. Pharmacol Biochem Behav 60：371-376, 1998

21）Sonnenberg JL, Rauscher FJ Ⅲ, Morgan JI, et al：Regulation of proenkephalin by Fos and Jun. Sciensce 246：1622-1625, 1989

22）Tokunaga A, Doi M, Senba E：Effects of local anaesthesia on formalin-induced Fos expression in the rat dorsal horn. Neuroreport 27：2301-2304, 1995

23）Umeno H, Nagasawa T, Yamazaki N, et al：Antinociceptive effects of repeated systemic injections of calcitonin in formalin-induced hyperalgesic rats. Pharmacol Biochem Behav 55：151-156, 1996