The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization
The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization
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DOI：
10.1016/j.pain.2006.04.014
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发表时间：
2006-06-01
期刊：
影响因子：
7.4
通讯作者：
Arendt-Nielson, Lars
中科院分区：
文献类型：
--
作者：
Gazerani, Parisa;Staahl, Camilla;Arendt-Nielson, Lars
三叉神经血管系统与偏头痛有关。A型肉毒毒素（BoNT-A）治疗偏头痛的疗效已在临床研究中进行了研究，但其作用机制尚未明确。假设BoNT-A抑制伤害性纤维的外周敏化并间接降低中枢敏化。我们研究了肌肉注射BoNT-A对前额皮内注射辣椒素诱导的三叉神经致敏的实验人体模型的影响。颅前肌内注射BoNT-A（肉毒杆菌素）或生理盐水。对32名健康男性志愿者的颈部和肩部肌肉进行双盲随机试验。皮内辣椒素引起的疼痛。治疗前、治疗后1周、4周、8周均出现光晕和继发性痛觉过敏。BoNT-A对疼痛、耀斑及痛觉过敏区均有明显的抑制作用。BoNT-A组疼痛强度面积（9.16 +/- 0.83 cm x s）明显小于生理盐水组（15.41 +/- 0.83 cm x s） （P = 0.011）。与生理盐水组（39.71 +/- 0.69 cm(2)）相比，BoNT-A组的斑块面积（29.81 +/- 0.69 cm(2)）也显著减少（p < 0.001）。同样，BoNT-A组继发性痛觉过敏的平均面积（4.25 +/- 0.91 cm(2)）明显小于生理盐水组（7.03 +/- 0.91 cm(2)） （P = 0.040）。事后分析显示，早在第1周，BoNT-A就对辣椒素诱导的感觉和血管舒缩反应有显著的抑制作用，两组试验之间存在显著差异（P < 0.001）。BoNT-A对前额皮内注射辣椒素激活的三叉/颈痛觉系统有抑制作用。这些影响可能是由BoNT-A对皮肤伤害感受器的局部外周作用引起的。(c) 2006国际疼痛研究协会。Elsevier B.V.版权所有。
The trigeminovascular system is involved in migraine. Efficacy of Botulinum Toxin type A (BoNT-A) in migraine has beef) investigated in clinical studies but the mechanism of action remains unexplored. It is hypothesized that BoNT-A inhibits peripheral sensitization of nociceptive fibers and indirectly reduces central sensitization. We examined the effect of intramuscular injection of BoNT-A on an experimental human model of trigeminal sensitization induced by intradermal capsaicin injection to the forehead. BoNT-A (BOTOX (R)) or saline was injected intramuscularly in precranial. neck and shoulder muscles to 32 healthy male volunteers in a double blind-randomized manner. Intradermally capsaicin-induced pain. flare and secondary hyperalgesia were obtained before and 1, 4 and 8 weeks after the above treatments. A significant suppressive effect of BoNT-A on pain, flare and hyperalgesia area was observed. The pain intensity area was significantly smaller in BoNT-A group (9.16 +/- 0.83 cm x s) compared to saline group (15.41 +/- 0.83 cm x s) (P = 0.011). The flare area was also reduced significantly in BoNT-A group (29.81 +/- 0.69 cm(2)) compared to saline group (39.71 +/- 0.69 cm(2)) (p < 0.001). Similarly, the mean area of secondary hyperalgesia was significantly Smaller in BoNT-A group (4.25 +/- 0.91 cm(2)) compared to saline group (7.03 +/- 0.91 cm(2)) (P = 0.040). Post hoc analysis showed significant differences across the trials with a remarkable suppression effect of BoNT-A off capsaicin-induced sensory and vasomotor reactions as early as week 1 (P < 0.001). BoNT-A presented suppressive effects on the trigeminal/cervical nociceptive system activated by intradermal injection of capsaicin to the forehead. The effects are suggested to be caused by a local peripheral effect of BoNT-A on cutaneous nociceptors. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.