Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Invest Ophthalmol Vis Sci. 2011 Feb 23;52(2):982-6. doi: 10.1167/iovs.10-6427. Print 2011 Feb.
Botulinum toxin A is the most commonly used treatment for blepharospasm, hemifacial spasm, and other focal dystonias. Its main drawback is its relatively short duration of effect. The goal of this study was to examine the ability of corticotropin releasing factor (CRF) or antibody to insulin growth factor I-receptor (anti-IGFIR) to reduce the up-regulation of neuromuscular junctions that are associated with return of muscle function after botulinum toxin treatment.
Eyelids of adult rabbits were locally injected with either botulinum toxin alone or botulinum toxin treatment followed by injection of either CRF or anti-IGFIR. After one, two, or four weeks, the orbicularis oculi muscles within the treated eyelids were examined for density of neuromuscular junctions histologically.
Injection of botulinum toxin into rabbit eyelids resulted in a significant increase in the density of neuromuscular junctions at one and two weeks, and an even greater increase in neuromuscular junction density by four weeks after treatment. Treatment with either CRF or anti-IGFIR completely prevented this increase in neuromuscular junction density.
The return of function after botulinum toxin-induced muscle paralysis is due to terminal sprouting and formation of new neuromuscular junctions within the paralyzed muscles. Injection with CRF or anti-IGFIR after botulinum toxin treatment prevents this sprouting, which in turn should increase the duration of effectiveness of single botulinum toxin treatments. Future physiology studies will address this. Prolonging botulinum toxin's clinical efficacy should decrease the number of injections needed for patient muscle spasm relief, decreasing the risk of negative side effects and changes in drug effectiveness that often occurs over a lifetime of botulinum toxin exposure.
肉毒杆菌毒素 A 是治疗眼睑痉挛、半面痉挛和其他局灶性肌张力障碍的最常用方法。其主要缺点是作用持续时间相对较短。本研究的目的是研究促肾上腺皮质释放因子（CRF）或胰岛素样生长因子 I 受体抗体（anti-IGFIR）是否能减少神经肌肉接头的上调，这与肉毒毒素治疗后肌肉功能的恢复有关。
成年兔的眼睑局部注射肉毒毒素或肉毒毒素治疗后注射 CRF 或 anti-IGFIR。在 1、2 或 4 周后，检查受治疗眼睑内的眼轮匝肌神经肌肉接头的密度。
向兔眼睑注射肉毒毒素可导致神经肌肉接头密度在 1 周和 2 周时显著增加，而在治疗后 4 周时甚至增加更多。用 CRF 或 anti-IGFIR 治疗可完全防止神经肌肉接头密度的增加。
肉毒毒素引起的肌肉瘫痪后功能的恢复是由于终末发芽和瘫痪肌肉内新的神经肌肉接头的形成。肉毒毒素治疗后注射 CRF 或 anti-IGFIR 可防止这种发芽，从而增加单次肉毒毒素治疗的有效时间。未来的生理学研究将对此进行探讨。延长肉毒毒素的临床疗效应减少患者肌肉痉挛缓解所需的注射次数，降低药物疗效随时间变化的风险，这种风险在肉毒毒素暴露的一生中经常发生。
