Subcutaneous administration of botulinum toxin A reduces formalin-induced pain
Subcutaneous administration of botulinum toxin A reduces formalin-induced pain
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DOI：
10.1016/j.pain.2003.10.008
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发表时间：
2004-01-01
期刊：
影响因子：
7.4
通讯作者：
Aoki, KR
中科院分区：
文献类型：
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作者：
Cui, ML;Khanijou, S;Aoki, KR
由肉毒梭菌产生的A型肉毒毒素(BoNT-A)是一种有效的神经肌肉接头乙酰胆碱释放抑制剂，已被用于治疗许多与肌肉过度收缩有关的疾病。然而，BoNT-A最近已被用于疼痛治疗，用于治疗肌筋膜痛、腰痛和包括偏头痛在内的各种类型的头痛。本研究旨在探讨BoNT-A在大鼠福尔马林炎性痛模型中的抗伤害作用及其机制。将BoNT-A(3.5、7、15和30U/kg)或赋形剂分别注射于雄性SD大鼠右后掌的足底。在福尔马林攻击前5天至12天，BoNT-A剂量依赖地(P<；0.05)在第二时相抑制福尔马林诱导的伤害性行为，但在第一时相不抑制。抗伤害性作用在用药前5h开始起效，持续至少12d。BoNT-A(7U/kg)也能减轻水肿。与福尔马林第一阶段缺乏作用一致，BoNT-A在15U/kg对急性热痛觉没有影响；在这个剂量下没有观察到局部肌肉无力。预先给予BoNT-A(3.5、7或15U/kg)均能显著降低福尔马林诱导的谷氨酸(Glu)释放。这些结果表明，局部外周注射BoNT-A显著减少了福尔马林诱导的伤害性行为，而没有明显的肌肉无力。BoNT-A的这种抗伤害性作用与抑制福尔马林诱导的谷氨酸(和/或神经肽)从初级传入终末释放有关。(C)2003年国际疼痛研究协会。爱思唯尔出版，版权所有。
Botulinum toxin type A (BoNT-A) produced by the bacterium Clostridium botulinum is a potent inhibitor of acetylcholine release in the neuromuscular junction and has been used to treat many disorders related to excessive muscle contraction. However, BoNT-A has recently been used in pain therapy to treat myofascial pain, low back pain and various types of headaches, including migraine. The purpose of this study is to investigate the antinociceptive effect of BoNT-A and its underlying mechanism in the rat formalin inflammatory pain model. BoNT-A (3.5, 7, 15 and 30 U/kg) or vehicle was administered to the plantar surface of the right hindpaw of male Sprague-Dawley rats. BoNT-A dose-dependently (P < 0.05) inhibited formalin-induced nociceptive behavior during phase 2 but not during phase I when administered 5 It to 12 days before formalin challenge. The onset of the antinociceptive effect started at 5 h after pre-treatment and this effect lasted for at least 12 days. BoNT-A (7 U/kg) also reduced edema. Consistent with the lack of effect in the formalin phase 1, BoNT-A, at 15 U/kg, had no effect on acute thermal nociception; no local muscle weakness was observed at this dose. Pre-treatment of rats with BoNT-A (3.5, 7 or 15 U/kg) all significantly reduced formalin-evoked glutamate (Glu) release. These results demonstrate that local peripheral injection of BoNT-A significantly reduces formalin-induced nociceptive behaviors with the absence of obvious muscle weakness. Such an antinociceptive effect of BoNT-A is associated with the inhibition of formalin-induced release of Glu (and/or neuropeptides) from primary afferent terminals. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.