一项新的研究表明，患有与子宫内膜异位症相关的慢性盆腔疼痛(CPP)的女性可能从A型肉毒杆菌毒素(肉毒杆菌，爱力根)的注射中受益，而不会出现明显的不良事件。
Botulinum toxin has been used successfully to treat back pain, migraine, and other neurological conditions including dystonia and spasticity.
肉毒毒素已被成功地用于治疗背痛、偏头痛和其他神经系统疾病，包括肌张力障碍和痉挛。
For this new study, "we were looking for people whose pain had persisted through all of that," said Karp.The researchers had some previous clinical experience in using botulinum toxin for CPP and had developed an injection technique. Early phase clinical trial results had been encouraging.
在这项新研究中，卡普说:“我们在寻找那些经历了所有痛苦的人。”研究人员有一些使用肉毒毒素治疗CPP的临床经验，并开发了一种注射技术。早期临床试验结果令人鼓舞。
The new randomized, double-masked placebo-controlled study included 29 premenopausal women ranging in age from 18 to 50 years (median age, 30 years) with CPP and documented endometriosis.
新的随机、双盲、安慰剂对照研究包括29名年龄从18岁到50岁(中位年龄30岁)的绝经前妇女，有CPP和有记录的子宫内膜异位症。
Study participants could not have another primary pain condition that might explain their pelvic pain.
研究参与者不可能有其他可能解释他们骨盆疼痛的主要疼痛状况。
Researchers carried out evaluations at baseline and at 1 month, including pelvic examinations to identify areas of pelvic floor spasms and a check on medication use.Investigators injected subjects trans-vaginally with either 100 units of botulinum toxin A or saline placebo.
研究人员在基线和1个月时进行了评估，包括盆腔检查以确定盆底痉挛的区域和检查药物使用情况。研究人员经阴道向受试者注射100单位的A型肉毒毒素或生理盐水安慰剂。
Injections were into pelvic floor muscles, with placement based on where the patient had pain and spasm, explained Stratton.At 100 units of toxin, the dose of the injection is "on the low side" when compared to the dose used to treat dystonia or spasticity, where a 300-unit range is typical, said Karp. To reduce wrinkles, an injection typically includes 20-50 units of toxin, she said.
斯特拉顿解释说，注射是在盆底肌肉，根据病人疼痛和痉挛的位置。卡普说，100单位的毒素，与治疗肌张力障碍或痉挛的300单位的剂量相比，注射剂量“偏低”。她说，为了减少皱纹，一次注射通常包含20-50个单位的毒素。
Study participants completed a pain visual analog scale (VAS) and assessed their response to the injection as: none, minimal, mild, moderate, or excellent.They also evaluated their disability as mild, moderate, severe, or crippling. Some people with CPP are quite immobilized while others are able to function at a higher level despite their pelvic pain, said Stratton."For some people, their disability may be an inability to have comfortable sexual intercourse; that interferes a little bit," but "not a lot" compared with patients who are "bedridden" with pain, she said.Second Injection
研究参与者完成了疼痛视觉模拟量表(VAS)，评估他们对注射的反应为:无、最小、轻微、中等或极好。他们还将自己的残疾评定为轻度、中度、重度或致残。斯特拉顿说，一些CPP患者非常僵硬，而另一些人尽管有盆腔疼痛，但仍能保持较高的功能水平。“对一些人来说，他们的残疾可能是无法进行舒适的*交性**;这有一点干扰，”但与那些因疼痛而“卧床不起”的病人相比，“不是很多”，她说。第二次注射
Study participants could request an open 100-unit botulinum toxin injection any time up to a year after the initial 1-month period.The toxin generally takes about a week to take effect and lasts about 3 months, at least when used for neurological indications, said Karp.
研究参与者可以在最初的1个月之后的任何时间要求100单位的肉毒杆菌毒素注射。卡普说，这种毒素通常需要大约一周的时间起效，持续约3个月，至少在用于神经指征时是这样。
"By 1 month, it should be just about at peak effect," she said."We didn't want the women who got the placebo to have to wait at least 3 months to get a second injection, so we used the request for a second injection at 1 month as another indicator of whether or not they had pain relief."The thinking, she added, was that the women who got the placebo might be more likely to ask for the second injection sooner than those who got the actual treatment.
她说:“1个月后，它应该刚好达到最佳效果。”“我们不想让服用安慰剂的女性等待至少3个月才能再次注射，所以我们使用在1个月后再次注射的请求作为她们是否缓解疼痛的另一个指标。”她补充说，她的想法是，接受安慰剂的女性可能比接受实际治疗的女性更有可能要求第二次注射。
The analysis showed that more women in the toxin group reported benefit than those in the placebo group.Of the 29 women randomized, 10 in the placebo group reported no benefit at 1 month compared to four in the botulinum toxin group (P = .048).
分析显示，毒素组比安慰剂组有更多的女性报告受益。在29名随机化的妇女中，安慰剂组有10名在1个月时没有获益，而肉毒毒素组有4名(P = .048)。
Those getting the active treatment reported a greater degree of benefit (P = .027).Women who reported no benefit in the placebo group at 1 month were more likely to request a second injection (odds ratio [OR], 7.94; 95% CI, 1.1 - 52.34; P = .032).Disability worsened in the placebo group but didn't change in the treatment group. Those with higher baseline disability were more likely to request an additional injection (OR, 1.11; 95% CI, 1.02 - 1.22; P = .217).At 1 month, only those receiving treatment had fewer muscle spasms.
接受积极治疗的患者获益程度更高(P = .027)。1个月时，报告安慰剂组无疗效的妇女更有可能要求第二次注射(优势比[OR]， 7.94;95% ci, 1.1 - 52.34;P = .032)。在安慰剂组残疾恶化，但在治疗组没有改变。基线残疾较高的患者更有可能要求额外注射(OR, 1.11;95% ci, 1.02 - 1.22;P = .217)。1个月后，只有接受治疗的患者肌肉痉挛减少。
As for pain medications, five patients treated with botulinum toxin reduced their use compared with only one in the placebo group. However, there was no change on pain ratings in either group.Transient adverse events included migraine, minor urinary symptoms (although no incontinence), and some aches. None of these was major, and they were similar in the two groups.
至于止痛药，五名接受肉毒杆菌毒素治疗的患者减少了使用，而安慰剂组只有一名患者减少了使用。然而，两组患者的疼痛评分没有变化。短暂的不良事件包括偏头痛、轻微的尿路症状(虽然没有大小便*禁失**)和一些疼痛。这些都不是主要的，而且在两组中是相似的。
"Statistically, there was no difference between those who got placebo and those who got active drug in terms of adverse events," said Stratton.Although there is no direct data to support long-term use of botulinum toxin for CPP, there is research showing that for other indications, "you can use it almost indefinitely," said Karp."I personally have treated people who have neurological disorders — dystonia and spasticity — with toxins for 30 years, so the odds are that you can use it long-term and retain benefit with repeated injections in patients with CPP.
斯特拉顿说:“从统计上看，服用安慰剂的患者和服用活*药性**物的患者在不良事件方面没有差异。”虽然没有直接数据支持长期使用肉毒杆菌毒素治疗CPP，但有研究表明，对于其他适应症，“你几乎可以无限期地使用它，”Karp说。“我个人用毒素治疗过神经障碍——肌张力障碍和痉挛——的患者30年了，所以你可以长期使用它，并在CPP患者反复注射中保持效益。
"For her part, Stratton wanted this new research to be a "proof of concept" for patients with endometriosis-related CPP."The obstetrics/gynecology community of which I'm a member has been obsessed with hormones and surgery," she said, adding that "it's really important" to have a more targeted strategy to treat pain."This might be a really novel way of thinking about how to approach persistent pain."The new results, said Stratton, "help to illustrate the cross communication between the muscles in our body and regions where we have pain."
对斯特拉顿来说，她希望这项新研究能成为子宫内膜异位症相关CPP患者的“概念证明”。我所在的妇产科社区一直痴迷于激素和手术，”她说，并补充说，有一个更有针对性的治疗疼痛的策略“真的很重要”。这可能是一种思考如何处理持续疼痛的非常新颖的方法。斯特拉顿说，新的结果“有助于说明我们身体肌肉和疼痛区域之间的交叉交流。”
But he noted that the study was relatively small. "This is good groundwork for future research into tailored treatment approaches, along with appropriately sized safety and efficacy studies."Zacharoff said the treatment should be used only in patients definitively diagnosed with pelvic floor muscle spasm "as opposed to using this treatment as a blanket for treating all types of pelvic pain."
但他指出，这项研究相对较小。“这是未来研究量身定制的治疗方法以及适当规模的安全性和有效性研究的良好基础。”Zacharoff表示，该疗法应仅用于明确诊断为盆底肌肉痉挛的患者，而不是将该疗法作为治疗所有类型盆腔疼痛的毯子。”