Kern Delphine, Pelle-Lancien Emilie, Luce Virginie, Bouhassira Didier
INSERM U-792, Centre d'Evaluation et de Traitement de la Douleur, CHU Ambroise Paré, 9, Avenue Charles de Gaulle, Boulogne-Billancourt F-92100, France Université Versailles-Saint-Quentin, Versailles F-78035, France.
Pain. 2008 Apr;135(3):291-299. doi: 10.1016/j.pain.2007.12.001. Epub 2008 Feb 6.
We investigated the role of the glutamatergic and endogenous opioidergic systems in the paradoxical pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin with a "thermal grill". Two parallel randomized, double-blind, cross-over studies, including two groups of 12 healthy volunteers, were carried out to compare the effects of i.v. ketamine or naloxone to those of placebo, on the sensations produced by a thermode (i.e. thermal grill) composed of six bars applied on the palmar surface of the right hand. The temperature of alternate (even- and odd-numbered) bars could be controlled independently by Peltier elements to produce various patterns of the grill. During each experimental session we measured the effects of ketamine, naloxone or placebo on the intensity of: (i) paradoxical pain; (ii) "normal" thermal (heat and cold) pain; and (iii) non-painful thermal (warm and cool) sensations. Ketamine administration resulted in a significant reduction of paradoxical pain intensity but did not alter normal pain or non-painful thermal sensations. By contrast, naloxone had no effect on paradoxical pain, normal pain or non-painful thermal sensations. This study demonstrates for the first time that the "thermal grill illusion of pain" can be modulated pharmacologically. This paradoxical pain, which involves the glutamatergic systems, acting through the NMDA receptors, but not the tonic endogenous opioids systems, might share some mechanisms with pathological pain.
我们研究了谷氨酸能和内源性阿片肽系统在通过“热格栅”同时对皮肤施加无害的热刺激和冷刺激所诱发的矛盾性疼痛中所起的作用。开展了两项平行的随机、双盲、交叉研究，每组包括12名健康志愿者，以比较静脉注射氯胺酮或纳洛酮与安慰剂对由应用于右手掌面的六条棒组成的温度刺激器（即热格栅）所产生感觉的影响。交替（偶数和奇数）棒的温度可通过珀耳帖元件独立控制，以产生格栅的各种模式。在每个实验环节中，我们测量了氯胺酮、纳洛酮或安慰剂对以下方面强度的影响：（i）矛盾性疼痛；（ii）“正常”热（热和冷）痛；以及（iii）非痛性热（温暖和凉爽）感觉。给予氯胺酮导致矛盾性疼痛强度显著降低，但未改变正常疼痛或非痛性热感觉。相比之下，纳洛酮对矛盾性疼痛、正常疼痛或非痛性热感觉均无影响。本研究首次证明“热格栅疼痛错觉”可通过药理学方法进行调节。这种涉及谷氨酸能系统、通过N-甲基-D-天冬氨酸受体起作用但不涉及紧张性内源性阿片肽系统的矛盾性疼痛，可能与病理性疼痛有一些共同机制。
