Department of Neurology and Psychiatry, University of Santo Tomas Hospital, España, 1008, Manila, Philippines.
Faculty of Medicine and Surgery, University of Santo Tomas, España, 1008, Manila, Philippines.
J Neural Transm (Vienna). 2020 Jun;127(6):935-951. doi: 10.1007/s00702-020-02163-5. Epub 2020 Mar 7.
Apart from the known efficacy of Botulinum Neurotoxin Type A (BoNT/A) in hyperactive striated and smooth muscles, different pain states have become potential targets of toxin effects. This present study determined the comparative toxin effectiveness in pain reduction among those patients injected with BoNT/A in muscle-based and in non-muscle-based conditions. Randomized controlled trials (RCTs) on the effect of BoNT/A on selected pain conditions were included. The conditions were spasticity and dystonia for muscle-based pain. For non-muscle-based pain, conditions included were painful diabetic neuropathy (PDN), post-herpetic neuralgia (PHN), trigeminal neuralgia (TN), complex regional pain syndrome (CRPS), and spinal cord injury (SCI). In view of possibly differing pathophysiology, myofascial pain, temporomandibular joint (TMJ), other joint or tendon pains, cervicogenic and lumbar pains, migraine and visceral pain syndromes were excluded. Standardized mean difference was used as the effect measure and computed with STATA. 25 RCTs were analyzed. Pooled estimates showed significantly lower pain score in the Treatment group (z = 5.23, p < 0.01, 95% CI = - 0.75, - 0.34). Subgroup analyses showed that BoNT/A significantly reduced both muscle-based (z = 3.78, p < 0.01, 95% CI = - 0.72, - 0.23) and non-muscle-based (z = 3.37, p = 0.001, 95% CI = - 1.00, - 0.27) pain. Meta-regression using four covariates namely dosage, route, frequency and duration was done which revealed that dosage significantly affects standardized mean differences, while the other three covariates were insignificant. The joint F-test was found to be insignificant (p value = 0.1182). The application of the model with these covariates does not significantly explain the derived heterogeneity of standardized mean differences. In conclusion, BoNT/A can be effectively used in muscle-based and non-muscle-based pain disorders. We detected no difference between the presence and magnitude of pain relief favoring muscle-based compared to non-muscle-based pain. Thus, we cannot say whether or not there might be independent mechanisms of toxin-induced pain relief for pain generated from either muscle or nerve hyperactivity.
除了已知的肉毒毒素 A（BoNT/A）在过度活跃的横纹肌和平滑肌中的疗效外，不同的疼痛状态已成为毒素作用的潜在靶点。本研究旨在确定在肌肉基础和非肌肉基础条件下注射 BoNT/A 的患者中，疼痛减轻的比较毒素效果。纳入了关于 BoNT/A 对选定疼痛状况影响的随机对照试验（RCT）。肌肉基础疼痛的条件包括痉挛和肌张力障碍。对于非肌肉基础疼痛，包括痛性糖尿病神经病变（PDN）、疱疹后神经痛（PHN）、三叉神经痛（TN）、复杂性区域疼痛综合征（CRPS）和脊髓损伤（SCI）。鉴于可能存在不同的病理生理学，排除了肌筋膜疼痛、颞下颌关节（TMJ）、其他关节或肌腱疼痛、颈源性和腰源性疼痛、偏头痛和内脏疼痛综合征。使用标准化均数差作为效应量，并使用 STATA 进行计算。分析了 25 项 RCT。汇总估计显示治疗组疼痛评分显著降低（z=5.23，p<0.01，95%CI=-0.75，-0.34）。亚组分析显示，BoNT/A 显著降低了肌肉基础（z=3.78，p<0.01，95%CI=-0.72，-0.23）和非肌肉基础疼痛（z=3.37，p=0.001，95%CI=-1.00，-0.27）。对四个协变量（剂量、途径、频率和持续时间）进行了多元回归分析，结果表明剂量显著影响标准化均数差，而其他三个协变量则不显著。联合 F 检验无显著性（p 值=0.1182）。应用这些协变量的模型不能显著解释标准化均数差的异质性。总之，BoNT/A 可有效用于肌肉基础和非肌肉基础疼痛障碍。我们没有发现肌肉基础疼痛缓解的存在和程度与非肌肉基础疼痛缓解的存在和程度之间存在差异。因此，我们不能说是否存在与肌肉或神经过度活跃引起的疼痛缓解相关的毒素诱导的疼痛缓解的独立机制。
