臨床整形外科48巻12号

2013年12月発行

誌上シンポジウム 慢性疼痛と原因療法―どこまで追究が可能か

抗サイトカインによる腰痛治療

著者： 大鳥精司¹ 西能健¹ 折田純久¹ 山内かづ代¹ 高橋和久¹

所属機関： ¹千葉大学大学院医学研究院・整形外科学

ページ範囲：P.1191 - P.1198

　ヒトや動物実験から導き出された腰痛，神経根性疼痛の基礎，臨床についてさまざまな報告がある．特に椎間板性腰痛，神経根性疼痛の病態として，サイトカインを中心とした炎症，それに物理的圧迫が作用し，神経障害をもたらすことが報告されている．最近ではこれらの研究結果をもとにさまざまな神経伸長因子や腫瘍壊死因子(TNFα)，インターロイキンを抑制するサイトカイン治療が行われつつある．これらの結果についても記載したい．

参考文献

1) Bogduk N, Tynan W, Wilson AS:The nerve supply to the human lumbar intervertebral discs. J Anat 132:39-56, 1981

2) Burke JG, Watson WG, McCormack D, et al:Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators. J Bone Joint Surg Br 84:196-201, 2002

3) Cohen SP, Wenzell D, Hurley RW, et al:A double-blind, placebo-controlled, dose-response pilot study evaluating intradiscal etanercept in patients with chronic discogenic low back pain or lumbosacral radiculopathy. Anesthesiology 107:99-105, 2007

4) Cohen SP, Bogduk N, Dragovich A, et al: Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Anesthesiology 110:1116-1126, 2009

5) Freemont AJ, Peacock TE, Goupille P, et al:Nerve ingrowth into diseased intervertebral disc in chronic back pain. Lancet 350:178-181, 1997

6) Igarashi A, Kikuchi S, Konno S, et al:Inflammatory cytokines released from the facet joint tissue in degenerative lumbar spinal disorders. Spine (Phila Pa 1976). 29(19):2091-2095, 2004

7) Kawakami M, Hashizume H, Nishi H, et al:Comparison of neuropathic pain induced by the application of normal and mechanically compressed nucleus pulposus to lumbar nerve roots in the rat. J Orthop Res 21:535-539, 2003

8) Korhonen T, Karppinen J, Malmivaara A, et al:Efficacy of infliximab for disc herniation-induced sciatica:one-year follow-up. Spine 29:2115-2119, 2004

9) Korhonen T, Karppinen J, Paimela L, et al:The treatment of disc herniation-induced sciatica with infliximab:results of a randomized, controlled, 3-month follow-up study. Spine 30:2724-2728, 2005

10) Lane NE, Schnitzer TJ, Birbara CA, et al:Tanezumab for the treatment of pain from osteoarthritis of the knee. N Engl J Med 363:1521-1531, 2010

11) McCarthy PW, Carruthers B, Martin D, et al:Immunohistochemical demonstration of sensory nerve fibers and endings in lumbar intervertebral discs of the rat. Spine 16:653-655, 1991

12) McCarthy PW, Petts P, Hamilton A:RT97-, calcitonin gene-related peptide-like immunoreactivity in lumbar intervertebral discs and adjacent tissue from the rat. J Anat 180:15-24, 1992

13) Ohtori S, Suzuki M, Koshi T, et al:Proinflammatory cytokines in the cerebrospinal fluid of patients with lumbar radiculopathy. Eur Spine J 20:942-946, 2011

14) Ohtori S, Miyagi M, Eguchi Y, et al:Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis:a prospective randomized study. Spine 37:439-444, 2012

15) Ohtori S, Miyagi M, Eguchi Y, et al:Efficacy of epidural administration of anti-interleukin-6 receptor antibody onto spinal nerve for treatment of sciatica. Eur Spine J 10:2079-2084, 2012

16) Omarker K, Myers RR:Pathogenesis of sciatic pain:role of herniated nucleus pulposus and deformation of spinal nerve root and dorsal root ganglion. Pain 78(2):99-105, 1998

17) Palmer EI, Lotz JC:The time-dependent role of cytokines in mechanically induced intervertebral disc degeneration. Trans Orthop Res Soc 29:128, 2004

18) Schwarzer AC, Aprill CN, Derby R, et al:The prevalence and clinical features of internal disc disruption in patients with chronic low back pain. Spine 20:1878-1883, 1995

19) Shinder V, Govrin-Lippmann R, Cohen S, et al:Structural basis of sympathetic-sensory coupling in rat and human dorsal root ganglia following peripheral nerve injury. J Neurocytol 28:743-761, 1999

20) Shinohara H:Lumbar disc lesion, with special reference to the histological significance of nerve endings of the lumbar discs. J Jpn Orthop Assoc 44:553-570, 1970

21) Takata K, Inoue S, Takahashi K, et al:Swelling of the cauda equina in patients who have herniation of a lumbar disc. A possible pathogenesis of sciatica. J Bone Joint Surg Am 70:361-368, 1988

22) Tobinick EL, Britschgi-Davoodifar S:Perispinal TNF-alpha inhibition for discogenic pain. Swiss Med Weekly 133:170-177, 2003

23) Toyone T, Takahashi K, Kitahara H, et al:Visualisation of symptomatic nerve roots. Prospective study of contrast-enhanced MRI in patients with lumbar disc herniation. J Bone Joint Surg Br 75:529-533, 1993

24) Ulrich JA, Liebenberg EC, Thuillier DU, et al:ISSLS prize winner:repeated disc injury causes persistent inflammation. Spine 32:2812-2819, 2007