Lacković Zdravko
Department of Pharmacology, University of Zagreb School of Medicine, Zagreb, Croatia.
Handb Exp Pharmacol. 2021;263:251-264. doi: 10.1007/164_2019_348.
This chapter is focused on analgesic mechanism of action of botulinum toxin type A (BoNT-A) including the action beyond peripheral nerve endings. With the exception of the meninges and possibly urinary bladder, the presence of BoNT-A activity in the periphery, cleaving SNAP25 as a target molecule, up to now was not convincingly shown. In contrast many reports demonstrated BoNT-A activity and the presence of cleaved SNAP25 in the brain and spinal cord. In a model of mirror pain BoNT-A analgesic effect can be achieved even without participation of peripheral nerve ending. Thus generalized hypothesis central or peripheral mechanism of action belongs to history, and there is a need to confirm or dispute the results with meninges, urinary bladder, and possibly with other, especially visceral organs.There are two general options for the central actions of BoNT-A: 1. The activity ends by silencing primary sensory neuron thereby stopping the pain information further in the CNS. 2. Or thereafter, indirectly or transsynaptically, BoNT-A triggers smaller or larger neural loops, forming memory of pain in the CNS that could explain the bilateral effects after unilateral peripheral administration, similar effect in mirror image allodynia and the like Intensive research has shown that peripherally administered BoNT-A reaches the CNS by axonal transport. There is increasing evidence that BoNT-A is preventing pain in a growing range of disorders. In the absence of unexpected findings, or an increase in the uncontrolled use of illicit preparations by uneducated persons, BoNT-A is emerging as a new long-lasting and relatively safe analgesic.
本章聚焦于A型肉毒毒素(BoNT-A)的镇痛作用机制,包括其在周围神经末梢以外的作用。除了脑膜和可能的膀胱外,目前尚无确凿证据表明外周存在BoNT-A活性并将SNAP25作为靶分子进行切割。相反,许多报告表明,BoNT-A活性以及切割后的SNAP25存在于脑和脊髓中。在镜像痛模型中,即使没有周围神经末梢的参与,也能实现BoNT-A的镇痛效果。因此,关于其作用机制是中枢性还是外周性的普遍假设已成为历史,需要对脑膜、膀胱以及可能的其他器官(尤其是内脏器官)的研究结果进行证实或反驳。BoNT-A的中枢作用有两种一般情况:1. 其活性通过使初级感觉神经元沉默而终止,从而在中枢神经系统中进一步阻止疼痛信息传递。2. 或者在此之后,BoNT-A间接或经突触触发大小不等的神经回路,在中枢神经系统中形成疼痛记忆,这可以解释单侧外周给药后的双侧效应、镜像性痛觉过敏中的类似效应等。深入研究表明,外周给予的BoNT-A通过轴突运输到达中枢神经系统。越来越多的证据表明,BoNT-A正在预防越来越多疾病中的疼痛。在没有意外发现或未受过教育的人非法制剂使用不受控制情况增加的前提下,BoNT-A正成为一种新型的长效且相对安全的镇痛药。