Greffrath Wolfgang, Nemenov Michael I, Schwarz Stefan, Baumgärtner Ulf, Vogel Hagen, Arendt-Nielsen Lars, Treede Rolf-Detlef
Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Saarstrasse 21, D-55099 Mainz, Germany.
Pain. 2002 Sep;99(1-2):145-55. doi: 10.1016/s0304-3959(02)00071-4.
Radiant heat is often used to study nociception in vivo. We now used infrared radiation generated by a diode laser stimulator (wavelength 980 nm) to investigate transduction mechanisms for noxious heat stimuli in acutely dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser stimulator offered the unique opportunity to test whether the same stimuli also elicit pain sensations in humans. A specific heat-induced current (I(heat)) was elicited in six of 13 small DRG neurons (diameter < or =30 microm) tested in the whole-cell configuration of the patch-clamp mode. Current responses in the seven heat-insensitive neurons were within the range explainable by the temperature dependence of the recording setup. I(heat) was characterized by: (1) non-linearity of its amplitude during a suprathreshold heat ramp as well as with stimuli of increasing intensity with an estimated threshold of 42 +/- 1 degrees C; (2) fast rise time and even faster decay time (t(1/2) = 96.5 +/- 5.9 and 27.7 +/- 1.5 ms, respectively); and (3) rate dependence of its induction. All three heat-sensitive neurons tested were also sensitive to capsaicin. The mean threshold for the induction of I(heat) was 2.8 +/- 0.3 J mm(-2). The threshold for the induction of action potentials by depolarizing current pulses was significantly reduced after laser stimulation, suggesting a sensitization at the transformation stage. No such change was seen in heat-insensitive neurons that underwent the same heat stimuli. The same diode laser elicited pain sensations and laser-evoked potentials in human subjects. No significant differences were seen between the pain thresholds in hairy and in glabrous skin, probably due to the deep penetration of this laser radiation. The mean pain threshold for stimuli > or =200 ms in humans was 2.5 +/- 0.2 J mm(-2) (n = 11), and did not differ from the thresholds for the induction of I(heat) in vitro. Our results indicate that I(heat) in primary sensory neurons can be activated by infrared laser pulses that are painful in humans.
辐射热常用于体内伤害感受的研究。我们现在使用二极管激光刺激器产生的红外辐射（波长980 nm）来研究体外急性分离的大鼠背根神经节（DRG）神经元中伤害性热刺激的转导机制。该激光刺激器提供了一个独特的机会来测试相同的刺激是否也会在人类中引发疼痛感。在膜片钳模式的全细胞配置中测试的13个小DRG神经元（直径≤30微米）中有6个引发了特定的热诱导电流（I(heat)）。7个对热不敏感的神经元中的电流反应在记录设置的温度依赖性可解释的范围内。I(heat)的特征为：（1）在阈上热斜坡期间以及刺激强度增加时其幅度呈非线性，估计阈值为42±1℃；（2）上升时间快，衰减时间甚至更快（t(1/2)分别为96.5±5.9和27.7±1.5毫秒）；（3）其诱导具有速率依赖性。测试的所有3个热敏感神经元也对辣椒素敏感。诱导I(heat)的平均阈值为2.8±0.3 J·mm(-2)。激光刺激后，通过去极化电流脉冲诱导动作电位的阈值显著降低，表明在转换阶段发生了敏化。在接受相同热刺激的热不敏感神经元中未观察到这种变化。同一二极管激光在人类受试者中引发了疼痛感和激光诱发电位。在有毛皮肤和无毛皮肤的疼痛阈值之间未观察到显著差异，这可能是由于这种激光辐射的深度穿透。在人类中，刺激≥200毫秒时的平均疼痛阈值为2.5±0.2 J·mm(-2)（n = 11），与体外诱导I(heat)的阈值无差异。我们的结果表明，初级感觉神经元中的I(heat)可被在人类中引起疼痛的红外激光脉冲激活。
