Greffrath Wolfgang, Baumgärtner Ulf, Treede Rolf-Detlef
Division of Neurophysiology, Center of Biomedicine and Medical Technology Mannheim (CBTM), Medical Faculty Mannheim, Ruprecht-Karls-University Heidelberg, Ludolf-Krehl-Str. 13-17, D-68167 Mannheim, Germany Institute of Physiology and Pathophysiology, Johanes Gutenberg-University, Saarstr. 21, D-55099 Mainz, Germany.
Pain. 2007 Dec 5;132(3):301-311. doi: 10.1016/j.pain.2007.04.026. Epub 2007 May 29.
For the neurophysiological examination of nociceptive pathways, contact-heat evoked potentials (contact-heat EPs) are elicited by repetitive brief noxious heat stimuli. Suppression of heat responses in primary nociceptive neurons during repetitive stimulation has been shown in animal models in vivo and in vitro. We now investigated whether heat pain and contact-heat EPs in humans display equivalent signs of habituation. Heat pain and EPs were elicited in 16 volunteers with a contact thermode (30 degrees Cs(-1)). Heat pulses at three intensities (pain threshold, moderate noxious and maximum available) were applied to the right forearm either by moving the thermode after each pulse to variable locations or when fixed to one location (inter-stimulus intervals 8-10s). Contact-heat EPs consisted of an early negativity in temporal leads (N1), followed by a biphasic response at the vertex (N2-P2). Pain ratings and contact-heat EPs (N1 and N2-P2 components) displayed significant temperature dependence. N2-P2 correlated positively with ratings. With stimulation at variable locations, both measures slowly decreased with time constants tau of 2 min (ratings) and 12 min (EPs). With stimulation at a fixed location, habituation was much faster for both, ratings (tau=10s) and EPs (tau=33 s). As a consequence, both measures were significantly reduced (p<0.005) leading to a rightward shift of the stimulus-response function by 5 degrees C. In conclusion, human heat pain perception and contact-heat EPs display signs of rapid habituation when stimulation is restricted to a fixed location and thus, reflect fatigue of peripheral nociceptive neurons. Habituation within the central nervous system is slower and less pronounced.
对于伤害性感受通路的神经生理学检查，接触热诱发电位（contact - heat EPs）由重复性短暂有害热刺激诱发。在体内和体外动物模型中均已显示，重复性刺激期间初级伤害性神经元的热反应受到抑制。我们现在研究人类的热痛和接触热诱发电位是否表现出等效的习惯化迹象。使用接触式热刺激器（30摄氏度每秒）在16名志愿者身上诱发热痛和诱发电位。通过在每次脉冲后将热刺激器移动到不同位置或固定在一个位置（刺激间隔8 - 10秒），以三种强度（疼痛阈值、中度有害和最大可用强度）的热脉冲施加到右前臂。接触热诱发电位包括颞叶导联的早期负波（N1），随后是头顶的双相反应（N2 - P2）。疼痛评分和接触热诱发电位（N1和N2 - P2成分）表现出显著的温度依赖性。N2 - P2与评分呈正相关。在不同位置进行刺激时，两种测量指标均随时间常数τ缓慢下降，疼痛评分的τ为2分钟，诱发电位的τ为12分钟。在固定位置进行刺激时，疼痛评分（τ = 10秒）和诱发电位（τ = 33秒）的习惯化都快得多。结果，两种测量指标均显著降低（p < 0.005），导致刺激 - 反应函数向右移动5摄氏度。总之，当刺激局限于固定位置时，人类热痛觉和接触热诱发电位表现出快速习惯化的迹象，因此反映了外周伤害性神经元的疲劳。中枢神经系统内的习惯化较慢且不太明显。
