Weissman-Fogel Irit, Sprecher Elliot, Granovsky Yelena, Yarnitsky David
Department of Neurology, Rambam Medical Center and Technion Faculty of Medicine, Haifa, Israel Department of Physiotherapy, Faculty of Health and Welfare, University of Haifa, Mount Carmel, Haifa, Israel.
Pain. 2003 Aug;104(3):693-700. doi: 10.1016/S0304-3959(03)00159-3.
Recent clinical studies showed that acute migraine attacks are accompanied by increased periorbital and bodily skin sensitivity to touch, heat and cold. Parallel pre-clinical studies showed that the underlying mechanism is sensitization of primary nociceptors and central trigeminovascular neurons. The present study investigates the sensory state of neuronal pathways that mediate skin pain sensation in migraine patients in between attacks. The assessments of sensory perception included (a) mechanical and thermal pain thresholds of the periorbital area, electrical pain threshold of forearm skin, (b) pain scores to phasic supra-threshold stimuli in the same modalities and areas as above, and (c) temporal summation of pain induced by applying noxious tonic heat pain and brief trains of noxious mechanical and electrical pulses to the above skin areas. Thirty-four pain-free migraine patients and 28 age- and gender-matched controls were studied. Patients did not differ from controls in their pain thresholds for heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6 mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for all modalities. They did, however, differ in their pain threshold for mechanical stimulation, just by one von Frey filament (P=0.01) and in their pain scores of the temporal summation tests. Increased summation of pain was found in migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS) +2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased summation corresponded with more severe clinical parameters of migraine and tended to depend on interval since last migraine attack. The absence of clinically or overt laboratory expressed allodynia suggests that pain pathways are not sensitized in the pain-free migraine patients. Nevertheless, the increased temporal summation, and the slight decrease in mechanical pain thresholds, suggest that central nociceptive neurons do express activation-dependent plasticity. These findings may point to an important pathophysiological change in membrane properties of nociceptive neurons of migraine patients; a change that may hold a key to more effective prophylactic treatment.
近期临床研究表明，急性偏头痛发作时伴有眶周及全身皮肤对触摸、热和冷的敏感性增加。同期临床前研究表明，其潜在机制是初级伤害感受器和中枢三叉神经血管神经元的致敏。本研究调查了偏头痛患者发作间期介导皮肤痛觉的神经通路的感觉状态。感觉知觉评估包括：（a）眶周区域的机械性和热痛阈值、前臂皮肤的电痛阈值；（b）与上述相同模式和区域的阈上阶段性刺激的疼痛评分；（c）对上述皮肤区域施加有害性温热痛以及短暂的有害性机械和电脉冲串所诱发疼痛的时间总和。研究了34名无疼痛的偏头痛患者和28名年龄及性别匹配的对照者。患者在热刺激（44±2.6 vs. 44.6±1.9℃）、电刺激（4.8±1.6 vs. 4.3±1.6 mA）的疼痛阈值以及所有模式阈上阶段性刺激的疼痛评分方面与对照者无差异。然而，他们在机械刺激的疼痛阈值上仅相差一根von Frey细丝（P = 0.01），且在时间总和测试的疼痛评分上存在差异。偏头痛患者在重复机械刺激（患者视觉模拟量表（VAS）变化值 +2.32±0.73 vs. 对照者 +0.16±0.83，P = 0.05）和重复电刺激（VAS变化值 +3.83±1.91 vs -3.79±2.31，P = 0.01）时疼痛总和增加。疼痛总和增加与偏头痛更严重的临床参数相关，且倾向于取决于自上次偏头痛发作以来的间隔时间。临床上或明显实验室检查未发现异常性疼痛表明，无疼痛的偏头痛患者的痛觉通路未致敏。然而，时间总和增加以及机械性疼痛阈值略有降低表明，中枢伤害性神经元确实表现出激活依赖性可塑性。这些发现可能指向偏头痛患者伤害性神经元膜特性的重要病理生理变化；这一变化可能是更有效预防性治疗的关键。
