臨床整形外科41巻4号

2006年04月発行

特集 脊椎脊髄病学 最近の進歩 2006（第34回日本脊椎脊髄病学会より）

慢性腰下肢痛症例に対する塩酸nicardipineくも膜下腔投与による中枢性感作治療の試み

著者： 村上孝徳¹ 山下敏彦² 石合純夫¹

所属機関： ¹札幌医科大学リハビリテーション医学 ²札幌医科大学整形外科

ページ範囲：P.473 - P.480

　慢性腰下肢痛の原因の1つとして脊髄後角における中枢感作の存在が考えられる．慢性腰下肢痛を訴える20症例に対して塩酸nicardipineくも膜下投与を行い，その鎮痛効果を検討した．VASによる疼痛自己評価では投与前9.3から最終経過観察時4.4と改善がみられていた．髄液中硝酸イオン濃度も同様に投与前26.4uM/Lから4週後15.4uM/Lと低下がみられた．Nicardipineによる鎮痛機序はNMDA-NO産生系の抑制にあるのではないかと考えられ，慢性疼痛において中枢感作が治療対象となりえる可能性がある．

参考文献

1）Bennett DLH, French J, Priestley JVP：NGF but not NT-3 or BDNF prevent the A fiber sprouting into lamina Ⅱ of the spinal cord that occurs following axotomy. Mol Cell Neurosci 8：211-220, 1996

2）Bonica JJ：Evolution and current status of pain programs. J Pain Symptom Manage 5：368-374, 1990

3）Bonica JJ：General consideration of chronic pain, In：Bonica JJ（ed）, The Manegement of Pain, Lea ＆ Febiger, Philadelphia, pp180-196, 1990

4）Brose WG, Gutlove D, Luther RR, et al：Use of intrathecal SNX-111, a novel, N-type, voltage-sensitive, calcium blocker, in the management of intractable brachial plexus avulsion pain. Clin J Pain 13：256-259, 1997

5）Chaplan SR, Malmberg AB, Yakch TL：Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve injury evoked allodynia in the rat. J Pharmacol Exp Ther 280：829-838, 1997

6）Coedrre TJ, Melzack R：The role of NMDA receptor-operated calcium channels in persistent nociception after formalin-induced tissue injury. J Neurosci 12：3671-3675, 1992

7）Cosgrove T, Nwachukwu C, Olakanmi O：The nitric oxide inhibitor L-NAME prolongs synaptic facilitation. Pioneering Neuroscience 6：27-29, 2005

8）Crue BL, Pinsky JJ：An approach to chronic pain of non-malignant origin. Postgrad Med J 60：858-864, 1984

9）Devor M, Seltzer Z：Pathophysiology of damaged nerve in relaton to chronic pain. In：Wall PD, Melzack R, editors. Textbook of Pain. 4th ed. Churchill Livingstone, Edinburgh, pp129-164, 1999

10）Diaz A, Dickenson AH：Blockade of spinal N-and P-type, but not L-type, calcium channels inhibits the excitability of rat dorsal horn neurones produced by subcutaneous formalin inflammation. Pain 69：93-100, 1997

11）Doan BD, Wadden NP：Relationship between depressive symptoms and descriptions of chronic pain. Pain 36：75-84, 1989

12）Dray A, Urban L, Dickenson A：Pharmacology of chronic pain. TiPS 15：190-197, 1994

13）Eisenberg E, Vos BP, Strassman AM：The NMDA antagonist Memantine blocks pain behavior in a rat model of formalin-induced facial pain. Pain 54：301-307, 1993

14）Hara K, Saito Y, Kirihara Y, et al：Antinociceptive effects of intrathecal L-type calcium channel blockers on visceral and somatic stimuli in the rat. Anesth Analg 87：382-387, 1998

15）Inoue T, Mashimo T, Shibata M：Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to the cGMP-mediated pathway in the rat neuropathic pain model. Brain res 792：263-270, 1998

16）伊藤誠二，南　敏明：痛みの生化学．生化学71：17-33, 1999

17）伊藤誠二：痛みの分子機構とGenetic Pharmacology．蛋白質 核酸 酵素44：1349-1359, 1999

18）Levine JD, Taiwo YO, Collins SD：Noradrenaline hyperalgesia is mediated through interaction with sympathetic postganglionic neurone terminals rather than activation of primary afferent nociceptors. Nature 323：158-169, 1986

19）Lewin GR, Mendell LM：Nerve growth factor and nociception. Trends Neurosci 16：353-359, 1993

20）Loeser JD. Concept of pain. In：Stanton HM, Boas RA（eds）. Chronic Low Back Pain. Raven Press, New York, p146, 1982

21）Malmberg A, Yaksh T：Spinal nitric oxide synthesis inhibition blocks NMDA-induced thermal hyperalgesia and produces antinociception in the formalin test in rats. Pain 54：291-300, 1993

22）McCathy RT, TanPiengco PE：Multiple type of high-threshold calcium channels in rabbit sensory neurons：High-affinity block of neuronal L-type by nimodipine. J Neurosci 12：2225-2234, 1992

23）Melzack R：Phantom limb pain：Imprications for treatment of pathologic pain. Anesthesiology 35：409-419, 1971

24）Merskey H, Bogduk N：Classification of Chronic Pain. IASP Press, Seattle, 1994

25）Neugebauer V, Vanegas J, Nebe J, et al：Effects of N-and L-Type calcium channel antagonists on the responses of nociceptive spinal cord neurons to mechanical stimulation of the normal and the inflamed knee joint. J Neurophysiol 76：3740-3749, 1996

26）佐伯　茂：難治性疼痛と慢性疼痛の概念．痛みと臨床1：288-294, 2001

27）塩谷雅弘：Multidiscriplinary pain clilnic.臨床神経科学20：1166-1167, 2002

28）Sluka KA：Blockade of calcium channels can prevent the onset of secondary hyperalgesia and allodynia induced by intradermal injection of capsaicin in rats. PAIN 71：157-164, 1997

29）Song WJ, Surmeier DJ：Voltage-dependent facilitation of calcium channels in rat neostratal neurons. J Neurosci 76：2290-2306, 1996

30）高橋三郎（訳）：DSM-Ⅳ．精神疾患の分類と診断の手引き．医学書院，東京；pp177-182, 1997

31）Vanegas H, Schaible HG：Effects of antagonists to high-threshold calcium channels upon spinal mechanisms of pain, hyperalgesia and allodynia. Pain 85：9-18, 2000

32）Wall PD, Devor M, Inbal FR：Autonomy following peripheral nerve lesions：experimental anesthesia dolorosa. Pain 7：103-113, 1979

33）Wermeling D, Drass M, Ellis D, et al：Pharmacokinetics and pharmacodynamics of intrathecal ziconotide in chronic pain patients. J Clin Pharmacol 43：624-636, 2003

34）Woolf CJ：Evidence for a central component of post-injury pain hypersensitivity. Nature 306：686-688, 1983

35）Woolf CJ, Thompson SW：The induction and maintenance of sentral sensitization is dependent on N-methyl-D-aspartic acid receptor acitivation；implications for the treatment of post-injury pain hypersensitivity states. Pain 44：293-299, 1991

36）Woolf CJ, Shortland P, Coggeshall RE：Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 355：75-77, 1992

37）Zhang JM, Donnelly DF, Song XJ：Axotomy increases the excitability of dorsal root ganglion cells with unmyelinated axons. J Neurophysiol 78：2790-2794, 1997