Namer Barbara, Kleggetveit Inge Petter, Handwerker Hermann, Schmelz Martin, Jorum Ellen
Department of Physiology and Pathophysiology, University of Erlangen, Universitätsstr. 17, 91054 Erlangen, Germany Department of Clinical Neurophysiology, Rikshospitalet, Oslo, Norway Department of Anesthesiology, Mannheim, University Heidelberg, Germany.
Pain. 2008 Sep 30;139(1):63-72. doi: 10.1016/j.pain.2008.03.007. Epub 2008 Apr 25.
Local cold injury often induces hypersensitivity to cold and cold allodynia. Sensitisation of TRPM8 or TRPA1 could be the underlying mechanisms. This was evaluated by psychophysics and axon-reflex-flare induction following topical menthol and cinnamaldehyde application in cold injury patients and healthy subjects. The patients had no signs of neuropathy except cold allodynia. We applied 20% cinnamaldehyde and 40% menthol solutions in the cold-allodynic area of the patients and in a corresponding area in healthy subjects and obtained sensory ratings during application. Thermotesting and Laser Doppler Imaging were performed before and after exposure to the compounds. Menthol did not induce axon-reflex-erythema in patients or in controls. After menthol cold pain threshold was decreased in healthy subjects; however, no further sensitisation was observed in the patients moreover in some patients an amelioration of their cold allodynia was observed. Cinnamaldehyde-induced pain sensation did not differ between patients and controls. Heat pain thresholds following cinnamaldehyde were lowered to a similar extent in patients and controls (43-39.8 and 44-39 degrees C) and also the axon-reflex-flare responses were comparable. No evidence for sensitisation of responses to TRPM8 or TRPA1-stimulation was found in patients with cold injury-induced cold allodynia. The lack of TRPM8 induced axon-reflex indicates that also de-novo expression of TRPM8 on mechano-insensitive C-nociceptors does not underlie cold allodynia in these patients. We conclude from these data that the mechanisms for the induction of cold allodynia in the patients with cold injury are independent of TRPM8 or TRPA1 and differ therefore from neuropathic pain patients.
局部冷损伤常诱发对冷的超敏反应和冷痛觉异常。TRPM8或TRPA1的致敏可能是其潜在机制。通过对冷损伤患者和健康受试者局部应用薄荷醇和肉桂醛后的心理物理学和轴突反射性潮红诱导来评估这一点。除冷痛觉异常外，患者无神经病变体征。我们在患者的冷痛觉异常区域以及健康受试者的相应区域应用20%肉桂醛和40%薄荷醇溶液，并在应用过程中获得感觉评分。在接触这些化合物之前和之后进行温度测试和激光多普勒成像。薄荷醇在患者或对照组中均未诱发轴突反射性红斑。在健康受试者中，薄荷醇应用后冷痛阈值降低；然而，在患者中未观察到进一步的致敏，而且在一些患者中观察到其冷痛觉异常有所改善。肉桂醛诱发的疼痛感觉在患者和对照组之间没有差异。肉桂醛应用后，患者和对照组的热痛阈值降低程度相似（分别为43 - 39.8℃和44 - 39℃），轴突反射性潮红反应也相当。在冷损伤诱导的冷痛觉异常患者中未发现对TRPM8或TRPA1刺激反应致敏的证据。缺乏TRPM8诱导的轴突反射表明，机械不敏感C类伤害感受器上TRPM8的从头表达也不是这些患者冷痛觉异常的基础。我们从这些数据得出结论，冷损伤患者中冷痛觉异常的诱导机制独立于TRPM8或TRPA1，因此与神经性疼痛患者不同。
