多发性硬化是中枢神经系统脱髓鞘性疾病，可导致患者出现多种功能障碍。疼痛是多发性硬化的常见症状，其临床表现多样，病理生理机制复杂，而常用镇痛药物的效果并不理想。肉毒素A除用于肌张力障碍性疾病的治疗外亦可用于镇痛，如三叉神经痛、偏头痛及痛性痉挛等，而这些疼痛类型均常见于多发性硬化。肉毒素A的镇痛机制可能与抑制炎症反应、减少离子通道活性及轴突逆向转运等作用有关。本文作者对肉毒素A治疗多发性硬化相关疼痛的研究作一综述。

[1] BROWNLEE W J,HARDY T A,FAZEKAS F,et al.Diagnosis of multiple sclerosis:progress and challenges[J].Lancet,2016,389(10076):1336-1346.
[2] TRUINI A,BARBANTI P,POZZILLI C,et al.A mechanism-based classification of pain in multiple sclerosis[J].Neurol,2013,260(2):351-367.
[3] YOUNG J,AMATYA B,GALEA M P,et al.Chronic pain in multiple sclerosis:a 10-year longitudinal study[J].Scand J Pain,2017,16(1):198-203.
[4] MARCK C H,De LIVERA A M,WEILAND T J,et al.Pain in people with multiple sclerosis:associations with modifiable lifestyle factors,fatigue,depression,anxiety,and mental health quality of life[J].Front Neurol,2017,5(8):461-467.
[5] DUTRA R C,BICCA M A,SEGAT G C,et al.The antinociceptive effects of the tetracyclic triterpene euphol in inflammatory and neuropathic pain models:the potential role of PKCÎμ[J].Neuroscience,2015,303(1):126-137.
[6] HASSLER S N,JOHNSON K M,HULSEBOSCH C E.Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical sensitivity in a chronic neuropathic pain model of spinal cord injury in rats[J].J Neurochem,2014,131(4):413-417.
[7] FINNERUP N B,HAROUTOUNIAN S,KAMERMAN P,et al.Neuropathic pain:an updated grading system for research and clinical practice[J].Pain,2016,157(8):1599-1606.
[8] FERRARO D,PLANTONE D,MORSELLI F,et al.Systematic assessment and characterization of chronic pain in multiple sclerosis patients[J].Neurol Sci,2017,9(7):1-9.
[9] YANG K Y,KIM M J,JU J S,et al.Antinociceptive effects of botulinum toxin type A on trigeminal neuropathic pain[J].J Dent Res,2016,95(10):1183-1190.
[10] MENG J,WANG J,STEINHOFF M,et al.TNF-α induces co-trafficking of TRPV1/TRPA1 in VAMP1-containing vesicles to the plasmalemma via Munc18-1/syntaxin1/SNAP-25 mediated fusion[J].Sci Rep,2016,6:21226.
[11] WU C,XIE N,LIAN Y,et al.Central antinociceptive activity of peripherally applied botulinum toxin type A in lab rat model of trigeminal neuralgia[J].Springerplus,2016,5(1):1-8.
[12] HARPER C B,PAPADOPULOS A,MARTIN S,et al.Botulinum neurotoxin type-A enters a non-recycling pool of synaptic vesicles[J].Sci Rep,2016,6:19654.
[13] MATAK I,RIEDERER P,LACKOVI Z.Botulinum toxin's axonal transport from periphery to the spinal cord[J].Neurochem Int,2012,61(2):236-239.
[14] WU C J,LIAN Y J,ZHENG Y K,et al.Botulinum toxin type A for the treatment of trigeminal neuralgia:results from a randomized,double-blind,placebo-controlled trial[J].Cephalalgia,2012,32(6):443-450.
[15] ZHANG H,LIAN Y,MA Y,et al.Two doses of botulinum toxin type A for the treatment of trigeminal neuralgia:observation of therapeutic effect from a randomized,double-blind,placebo-controlled trial[J].J Headache Pain,2014,15:65.
[16] MORRA M E,ELGEBALY A,ELMARAEZY A,et al.Therapeutic efficacy and safety of botulinum toxin A therapy in trigeminal neuralgia:a systematic review and meta-analysis of randomized controlled trials[J].J Headache Pain,2016,17(1):63.
[17] PATIL S,WILLETT O,THOMPKINS T,et al.Botulinum toxin:pharmacology and therapeutic roles in pain states[J].Curr Pain Headache Rep,2016,20(3):1-8.
[18] MOISSET X,OUCHCHANE L,GUY N,et al.Migraine headaches and pain with neuropathic characteristics:comorbid conditions in patients with multiple sclerosis[J].Pain,2013,154(12):2691-2699.
[19] JI R R,XU Z Z,GAO Y J.Emerging targets in neuroinflammation-driven chronic pain[J].Nat Rev Drug Discov,2014,13(7):533-548.
[20] CUI M,KHANIJOU S,RUBINO J,et al.Subcutaneous administration of botulinum toxin A reduces formalin-induced pain[J].Pain,2004,107(1-2):125-133.
[21] LUCIONI A,BALES G T,LOTAN T L,et al.Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation[J].BJU Int,2008,101(3):366-370.
[22] AURORA S K,DODICK D W,DIENER H C,et al.OnabotulinumtoxinA for chronic migraine:efficacy,safety,and tolerability in patients who received all 5 treatment cycles in PREEMPT[J].Acta Neurol Scand,2014,129(1):61-70.
[23] BLUMENFELD A M,STARK R J,FREEMAN M C,et al.Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine:COMPEL study[J].J Headache Pain,2018,19(1):13.
[24] RESTIVO D A,TINAZZI M,PATTI F,et al.Botulinum toxin treatment of painful tonic spasms in multiple sclerosis[J].Neurology,2004,62(11):2143.