肉毒杆菌毒素：作用机制、镇痛作用和临床应用,Toxicology

肉毒杆菌毒素 (BoNT) 是一种强效神经毒素，由革兰氏阳性、孢子形成、厌氧细菌肉毒杆菌产生。肉毒毒素有 7 种已知的免疫学上不同的血清型：A、B、C1、D、E、F 和 G 型。梭状芽胞杆菌神经毒素以 150  kDa 的单条无活性多肽链形式产生，被组织蛋白酶切割成活性肽链。 -链分子：~100 kDa 的重链 (H) 和 ~50 kDa 的轻链 (L) kDa 通过单个二硫键结合在一起。每种血清型都表现出其不同的作用机制和作用持续时间。每种 BoNT 血清型的重链与其特定的神经元外受体结合，从而发生细胞内突触小泡的膜易位和内吞作用。轻链的作用是切割 SNAP-25，从而抑制突触胞吐作用，因此禁用神经传递。肉毒毒素阻断神经肌肉接头处乙酰胆碱肉毒杆菌毒素释放的作用是最好的理解，然而，大多数专家承认，仅此作用似乎不足以解释神经毒素明显的镇痛活性的全部。最后，

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Botulinum toxin (BoNT) is a potent neurotoxin that is produced by the gram-positive, spore-forming, anaerobic bacterium, Clostridum botulinum. There are 7 known immunologically distinct serotypes of BoNT: types A, B, C1, D, E, F, and G. Clostridum neurotoxins are produced as a single inactive polypeptide chain of 150 kDa, which is cleaved by tissue proteinases into an active di-chain molecule: a heavy chain (H) of ∼100 kDa and a light chain (L) of ∼50 kDa held together by a single disulfide bond. Each serotype demonstrates its own varied mechanisms of action and duration of effect. The heavy chain of each BoNT serotype binds to its specific neuronal ecto-acceptor, whereby, membrane translocation and endocytosis by intracellular synaptic vesicles occurs. The light chain acts to cleave SNAP-25, which inhibits synaptic exocytosis, and therefore, disables neural transmission. The action of BoNT to block the release of acetylcholine botulinum toxin at the neuromuscular junction is best understood, however, most experts acknowledge that this effect alone appears inadequate to explain the entirety of the neurotoxin's apparent analgesic activity. Consequently, scientific and clinical evidence has emerged that suggests multiple antinociceptive mechanisms for botulinum toxins in a variety of painful disorders, including: chronic musculoskeletal, neurological, pelvic, perineal, osteoarticular, and some headache conditions.