Craig A D, Andrew D
Atkinson Pain Research Laboratory, Division of Neurosurgery, Barrow Neurological Institute, Phoenix, Arizona 85013, USA.
J Neurophysiol. 2002 Apr;87(4):1902-14. doi: 10.1152/jn.00578.2001.
It was recently shown that repeated heat stimulation, using brief contacts (<1 s) with a preheated thermode at sufficiently short interstimulus intervals (ISIs <5 s) and high temperatures (> or =51 degrees C), will elicit in humans a sensation of rapidly augmenting "second" (burning) pain with only a weak "first" (sharp) pain sensation. Most strikingly, at short intertrial intervals (ITIs >5 s) such summation will reset, or begin again at baseline. In the present experiments, the responses of nociceptive lamina I spinothalamic (STT) neurons in the lumbosacral dorsal horn of barbiturate-anesthetized cats were examined using this repeated brief contact heat paradigm. The neurons were classified as nociceptive-specific (NS, n = 8) or polymodal nociceptive (HPC, n = 8) based on their responses to quantitative thermal stimuli; all had receptive fields on the glabrous ventral hindpaw. A pneumatic piston was used to apply a thermode preheated to 34, 46, 49, 53, or 58 degrees C with a contact dwell time of approximately 0.7 s to the ventral hindpaw repeatedly (15 times) at ISIs of 2, 3, and 5 s, with 3-5 min between trials. The mean responses of the 16 nociceptive lamina I STT cells showed rapid temporal summation that was directly dependent on temperature and inversely dependent on ISI, with the greatest increases occurring between the 3rd and 10th contacts. The temporal profiles of this family of curves correspond with the psychophysical data on human sensation. Further analysis showed that this summation was due to the HPC cells, which all showed strong summation; in contrast, the NS cells showed little, if any. The HPC responses to the repeated heat stimuli lagged each contact by approximately 1 s, consistent with the strong, monosynaptic C-fiber input that is characteristic of HPC cells and also with the dependence of second pain on C-fiber nociceptors. HPC cells also displayed the reset phenomenon at short ITIs, again in correspondence with the psychophysical data. The summation and the reset displayed by HPC cells were not related to skin temperature. Thus the results presented in this study, together with those in the preceding article, demonstrate a double dissociation indicating that NS and HPC lamina I STT cells can subserve the qualitatively distinct sensations of first (sharp) and second (burning) pain, respectively. These findings support the concept that the lamina I STT projection comprises several discrete sensory channels that are integrated in the forebrain to generate distinct sensations.
最近的研究表明，在足够短的刺激间隔（ISI<5秒）和高温（≥51摄氏度）下，使用预热的热刺激器与皮肤进行短暂接触（<1秒）的反复热刺激，会在人类身上引发一种迅速增强的“第二”（灼痛）疼痛感觉，而“第一”（刺痛）疼痛感觉则很微弱。最引人注目的是，在短的试验间隔（ITI>5秒）时，这种总和会重置，或者从基线重新开始。在本实验中，使用这种反复短暂接触热刺激范式，研究了巴比妥麻醉猫腰骶背角中伤害性I层脊髓丘脑束（STT）神经元的反应。根据神经元对定量热刺激的反应，将其分为伤害性特异性（NS，n = 8）或多模式伤害性（HPC，n = 8）；所有神经元在无毛的后爪腹侧都有感受野。使用气动活塞将预热到34、46、49、53或58摄氏度的热刺激器以约0.7秒的接触停留时间反复（15次）施加到后爪腹侧，刺激间隔为2、3和5秒，两次试验之间间隔3-5分钟。16个伤害性I层STT细胞的平均反应显示出快速的时间总和，这直接取决于温度，反比于刺激间隔，最大的增加发生在第3次到第10次接触之间。这一系列曲线的时间分布与人类感觉的心理物理学数据相对应。进一步分析表明，这种总和是由于HPC细胞引起的，它们都表现出强烈的总和；相比之下，NS细胞几乎没有表现出总和（如果有的话）。HPC细胞对反复热刺激的反应比每次接触滞后约1秒，这与HPC细胞特有的强烈单突触C纤维输入一致，也与第二疼痛对C纤维伤害感受器的依赖性一致。HPC细胞在短的试验间隔时也表现出重置现象，同样与心理物理学数据一致。HPC细胞表现出的总和和重置与皮肤温度无关。因此，本研究中呈现的结果与前文的结果一起，证明了一种双重分离，表明NS和HPC I层STT细胞可以分别服务于性质上不同的第一（刺痛）和第二（灼痛）疼痛感觉。这些发现支持了这样一种概念，即I层STT投射包括几个离散的感觉通道，这些通道在前脑整合以产生不同的感觉。
