Minneapolis VA Health Care System, Minneapolis, MN 55455, USA.
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Toxins (Basel). 2020 May 10;12(5):314. doi: 10.3390/toxins12050314.
Chronic osteoarthritis pain is an increasing worldwide problem. Treatment for osteoarthritis pain is generally inadequate or fraught with potential toxicities. Botulinum toxins (BoNTs) are potent inhibitors of neuropeptide release. Paralytic toxicity is due to inhibition at the neuromuscular junction, and this effect has been utilized for treatments of painful dystonias. Pain relief following BoNT muscle injection has been noted to be more significant than muscle weakness and hypothesized to occur because of the inhibition of peripheral neuropeptide release and reduction of peripheral sensitization. Because of this observation, BoNT has been studied as an intra-articular (IA) analgesic for chronic joint pain. In clinical trials, BoNT appears to be effective for nociceptive joint pain. No toxicity has been reported. In preclinical models of joint pain, BoNT is similarly effective. Examination of the dorsal root ganglion (DRG) and the central nervous system has shown that catalytically active BoNT is retrogradely transported by neurons and then transcytosed to afferent synapses in the brain. This suggests that pain relief may also be due to the central effects of the drug. In summary, BoNT appears to be safe and effective for the treatment of chronic joint pain. The long-term effects of IA BoNT are still being determined.
慢性骨关节炎疼痛是一个日益严重的全球性问题。骨关节炎疼痛的治疗通常是不够的，或者存在潜在的毒性。肉毒毒素（BoNTs）是神经肽释放的有效抑制剂。瘫痪毒性是由于在运动终板的抑制，这种效果已被用于治疗疼痛性肌张力障碍。肉毒毒素肌肉注射后的疼痛缓解比肌肉无力更显著，并假设其发生是因为抑制外周神经肽的释放和减少外周致敏。由于这一观察，肉毒毒素已被研究为一种关节内（IA）镇痛剂，用于治疗慢性关节疼痛。在临床试验中，肉毒毒素似乎对伤害感受性关节疼痛有效。没有报道毒性。在关节疼痛的临床前模型中，肉毒毒素同样有效。对背根神经节（DRG）和中枢神经系统的检查表明，催化活性的肉毒毒素被神经元逆行运输，然后被转胞吞运到大脑中的传入突触。这表明，疼痛缓解也可能是由于药物的中枢作用。总之，肉毒毒素似乎是安全有效的，可用于治疗慢性关节疼痛。IA 肉毒毒素的长期效果仍在确定中。
