Obermann Mark, Diener Hans-Christoph
Curr Treat Options Neurol. 2009 Jan;11(1):24-31. doi: 10.1007/s11940-009-0004-x.
The discrepancy between the widespread use of botulinum neurotoxin (BoNT) in managing headache and the supporting clinical evidence is unprecedented. No substance seems to have inspired more physicians and patients to undertake spirited treatment attempts. Tremendous treatment success in small, uncontrolled clinical trials has been repeatedly reported, but no substance that has been studied to an equal extent has so utterly failed to provide proof of effect in controlled clinical trials. Nevertheless, even though most randomized, controlled clinical trials have not met their defined primary outcome criterion, BoNT is still considered a promising treatment alternative for primary headache disorders. Experimental approaches to the pathophysiologic impact of BoNT on the perception of pain have been equally unsuccessful. Although most studies have been unable to find a direct antinociceptive effect in humans, some researchers continue to seek specific injection sites or injection techniques that may promise more successful results. Others look for a positive effect by narrowing the indications for BoNT to more homogenous symptoms or special patient subgroups. The results of randomized, controlled studies involving a total of 3552 patients indicate that BoNT injection is probably ineffective for patients with migraine and chronic tension-type headache regardless of injection site, dosage, or injection regimen, and there is insufficient evidence to draw a conclusion about its effectiveness for the treatment of chronic daily headache or subforms. The lack of direct experimental or clinical trial evidence that BoNT has a direct antinociceptive effect in humans must be addressed before more trials are conducted, involving even more patients. Additional pathophysiologically oriented research is also needed to unravel the mechanisms of action of BoNT in human pain perception or, alternatively, to bring it all down to the placebo effect.
肉毒杆菌神经毒素（BoNT）在头痛治疗中的广泛应用与支持性临床证据之间的差异是前所未有的。似乎没有哪种物质能激发更多医生和患者积极尝试治疗。小型非对照临床试验中屡屡报告了巨大的治疗成功，但在同等程度研究的物质中，没有一种在对照临床试验中如此彻底地未能提供疗效证据。然而，尽管大多数随机对照试验未达到其定义的主要结局标准，但BoNT仍被认为是原发性头痛疾病的一种有前景的治疗选择。关于BoNT对疼痛感知的病理生理影响的实验方法同样未取得成功。尽管大多数研究未能在人体中发现直接的镇痛作用，但一些研究人员仍在继续寻找可能带来更成功结果的特定注射部位或注射技术。其他人则通过将BoNT的适应症缩小到更同质的症状或特殊患者亚组来寻找积极效果。涉及总共3552名患者的随机对照研究结果表明，无论注射部位、剂量或注射方案如何，BoNT注射对偏头痛和慢性紧张型头痛患者可能无效，并且没有足够的证据就其对慢性每日头痛或亚型的治疗效果得出结论。在进行更多涉及更多患者的试验之前，必须解决缺乏BoNT在人体中具有直接镇痛作用的直接实验或临床试验证据这一问题。还需要进行更多以病理生理学为导向的研究，以阐明BoNT在人类疼痛感知中的作用机制，或者，将其归结为安慰剂效应。
