肉毒杆菌毒素
肉毒杆菌毒素已被证明能够抑制非胆碱能神经传递素从感觉神经末梢释放(阻滞乙酰胆碱胞吐作用的效果除外)。当通过部分皮内注射给予时,其已改善了 25 例局灶性疼痛性神经病的神经性疼痛症状,[89]Ranoux D, Attal N, Morain F, et al. Botulinum type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol. 2008;64:274-283.http://www.ncbi.nlm.nih.gov/pubmed/18546285?tool=bestpractice.com 并在与交感神经阻滞一起使用时已延长了一小部分 CRPS 患者中镇痛的持续时间。[90]Carroll I, Clark JD, Mackey S. Sympathetic block with botulinum toxin to treat complex regional pain syndrome. Ann Neurol. 2009;65:348-351.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763598/?tool=pubmedhttp://www.ncbi.nlm.nih.gov/pubmed/19334078?tool=bestpractice.com
N-甲基-D-天冬氨酸受体阻滞剂
各种证据证明,谷氨酸在慢性神经性疼痛中可能起到一定的作用,而且阻滞其一个受体类型 - N-甲基-D-天冬氨酸 (NMDA) 受体可能会让难治性患者在临床上有所改善。已按照麻醉和亚麻醉剂量静脉内给予氯胺酮,疗效良好但各异。[91]Kiefer RT, Rohr R, Ploppa A, et al. A pilot open-label study of the efficacy of subanesthetic isomeric S(+)-ketamine in refractory CRPS patients. Pain Med. 2008;9:44-54.http://www.ncbi.nlm.nih.gov/pubmed/18254766?tool=bestpractice.com[92]Correll GE, Maleki J, Gracely EJ, et al. Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome. Pain Med. 2004;5:263-275.http://www.ncbi.nlm.nih.gov/pubmed/15367304?tool=bestpractice.com[93]Kiefer RT, Rohr R, Ploppa A, et al. Complete recovery from intractable complex regional pain syndrome, CRPS-type 1, following anesthetic ketamine and midazolam. Pain Pract. 2007;7:147-150.http://www.ncbi.nlm.nih.gov/pubmed/17559485?tool=bestpractice.com[94]Schwartzman RJ, Alexander GM, Grothusen JR, et al. Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study. Pain. 2009;147:107-115.http://www.ncbi.nlm.nih.gov/pubmed/19783371?tool=bestpractice.com[95]Azari P, Lindsay DR, Briones D, et al. Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review. CNS Drugs. 2012;26:215-228.http://www.ncbi.nlm.nih.gov/pubmed/22136149?tool=bestpractice.com 如何使用该药、以什么剂量以及在什么时间段尚不清楚。仍有必要进行进一步研究,以确认这些 NMDA 受体阻滞剂的功效。[96]Collins S, Sigtermans MJ, Dahan A, et al. NMDA receptor antagonists for the treatment of neuropathic pain. Pain Med. 2010;11:1726-1742.http://www.ncbi.nlm.nih.gov/pubmed/21044263?tool=bestpractice.com[97]Gustin SM, Schwarz A, Birbaumer N, et al. NMDA-receptor antagonist and morphine decrease CRPS-pain and cerebral pain representation. Pain. 2010;151:69-76.http://www.ncbi.nlm.nih.gov/pubmed/20630656?tool=bestpractice.com
自由基清除剂
基于炎症有助于发展为 CRPS 且与氧自由基的产生有关,已尝试自由基清除剂(二甲基亚砜 50% 和 N-乙酰半胱氨酸),并取得了一定的成功。[98]Perez RS, Zuurmond WW, Bezemer PD, et al. The treatment of complex regional pan syndrome type I with free radical scavengers: a randomized controlled study. Pain. 2003;102:297-307.http://www.ncbi.nlm.nih.gov/pubmed/12670672?tool=bestpractice.com
运动皮层刺激
这增加了丘脑、导叶和前额皮质中的局部血流量,从而调节疼痛的情感体验和抑制丘脑机能亢进。[31]Lima MC, Fregni F. Motor cortex stimulation for chronic pain: systematic review and meta-analysis of the literature. Neurology. 2008;70:2329-2337.http://www.ncbi.nlm.nih.gov/pubmed/18541887?tool=bestpractice.com[32]Andre-Obadia N, Mertens P, Gueguen A, et al. Pain relief by rTMS: differential effect of current flow but no specific action on pain subtypes. Neurology. 2008;71:833-840.http://www.ncbi.nlm.nih.gov/pubmed/18779511?tool=bestpractice.com 较之经颅磁刺激治疗法(无创),直接皮层刺激(有创)在神经性疼痛患者中可能更有效。[31]Lima MC, Fregni F. Motor cortex stimulation for chronic pain: systematic review and meta-analysis of the literature. Neurology. 2008;70:2329-2337.http://www.ncbi.nlm.nih.gov/pubmed/18541887?tool=bestpractice.com虽然 CRPS 是一种神经性疼痛状态,但在 CRPS 患者中尚未充分测试这些疗法。
免疫调节剂
炎症可能在 CRPS 病理生理学中发挥作用。因此,减少炎症的糖皮质激素、肿瘤坏死因子 α 拮抗药、沙立度胺、双磷酸盐和免疫球蛋白等免疫调节剂可能具有治疗 CRPS 的作用。[99]Dirckx M, Stronks DL, Groeneweg G, et al. Effect of immunomodulating medications in complex regional pain syndrome: a systematic review. Clin J Pain. 2012;28:355-363.http://www.ncbi.nlm.nih.gov/pubmed/22001668?tool=bestpractice.com然而,需更多高质量研究来完全确定这些制剂在 CRPS 中的益处。已在少数患者中尝试了静脉内免疫球蛋白,有时会得出阳性结果。[24]Goebel A, Blaes F. Complex regional pain syndrome, prototype of a novel kind of autoimmune disease. Autoimmun Rev. 2013;12:682-686.http://www.ncbi.nlm.nih.gov/pubmed/23219953?tool=bestpractice.com