Edelmayer Rebecca M, Ossipov Michael H, Porreca Frank
Department of Pharmacology, The University of Arizona, Tucson, AZ, USA.
Methods Mol Biol. 2012;851:109-20. doi: 10.1007/978-1-61779-561-9_7.
Migraine patients often demonstrate cutaneous allodynia, defined as a hypersensitivity of the skin to touch or mechanical stimuli that are normally innocuous. The allodynia sometimes begins intracranially and spreads, via unknown mechanisms, to extracranial regions. The goal of the study was to develop and validate a model of cutaneous allodynia triggered by dural inflammation for this aspect of pain associated with headaches. Inflammatory mediators (IM) were applied to the dura of non-anesthetized rats via previously implanted cannulas and sensory thresholds of the face and hindpaws were characterized. IM elicited robust and time-related facial and hindpaw allodynia which peaked after approximately 3 h. These effects were reminiscent of cutaneous allodynia seen in patients with migraine or other primary headache conditions, and were reversed by agents used clinically in the treatment of migraine. Facial and hindpaw allodynia associated with dural stimulation is a useful surrogate of allodynia associated with primary headache including migraine likely reflecting the development of central sensitization and may be exploited mechanistically for the development of novel therapeutic strategies for headache pain.
偏头痛患者常表现出皮肤异痛症,其定义为皮肤对通常无害的触摸或机械刺激产生超敏反应。这种异痛症有时始于颅内,并通过未知机制扩散至颅外区域。本研究的目的是针对与头痛相关的这一疼痛方面,开发并验证一种由硬脑膜炎症引发的皮肤异痛症模型。通过先前植入的套管将炎症介质(IM)应用于未麻醉大鼠的硬脑膜,并对其面部和后爪的感觉阈值进行表征。IM引发了强烈且与时间相关的面部和后爪异痛症,约3小时后达到峰值。这些效应让人联想到偏头痛或其他原发性头痛疾病患者中出现的皮肤异痛症,并且可被临床上用于治疗偏头痛的药物逆转。与硬脑膜刺激相关的面部和后爪异痛症是与包括偏头痛在内的原发性头痛相关的异痛症的有用替代指标,可能反映了中枢敏化的发展,并且可以从机制上用于开发治疗头痛疼痛的新治疗策略。