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 A 型肉毒杆菌神经毒素 (BoNT/A) 在过度活跃的横纹肌和平滑肌中的已知功效外，不同的疼痛状态已成为毒素效应的潜在目标。本研究确定了在肌肉型和非肌肉型条件下注射 BoNT/A 的患者在减轻疼痛方面的毒素效果比较。包括关于 BoNT/A 对选定疼痛状况影响的随机对照试验 (RCT)。条件是基于肌肉的疼痛的痉挛和肌张力障碍。对于非肌肉疼痛，包括疼痛性糖尿病神经病变 (PDN)、带状疱疹后神经痛 (PHN)、三叉神经痛 (TN)、复杂区域疼痛综合征 (CRPS) 和脊髓损伤 (SCI)。鉴于可能不同的病理生理、肌筋膜疼痛、颞下颌关节 (TMJ)、排除其他关节或肌腱痛、颈源性和腰痛、偏头痛和内脏疼痛综合征。使用标准化平均差作为效应量度并使用 STATA 计算。分析了 25 个 RCT。汇总估计显示治疗组的疼痛评分显着降低（z  = 5.23, p  < 0.01, 95% CI = – 0.75, – 0.34)。亚组分析显示 BoNT/A 显着降低基于肌肉的 ( z  = 3.78, p  < 0.01, 95% CI = – 0.72, – 0.23) 和非肌肉 ( z  = 3.37, p  = 0.001, 95% CI) = – 1.00, – 0.27) 疼痛。使用四个协变量即剂量、途径、频率和持续时间进行元回归，结果表明剂量显着影响标准化平均差异，而其他三个协变量不显着。联合F检验被发现不显着（p值 = 0.1182）。具有这些协变量的模型的应用并不能显着解释标准化平均差异的衍生异质性。总之，BoNT/A 可以有效地用于基于肌肉和非基于肌肉的疼痛疾病。与非肌肉疼痛相比，我们发现有利于基于肌肉的疼痛缓解的存在和程度之间没有差异。因此，对于肌肉或神经过度活跃产生的疼痛，我们不能说是否存在毒素诱导的疼痛缓解的独立机制。