Yamamura H, Malick A, Chamberlin N L, Burstein R
Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Neurophysiol. 1999 Feb;81(2):479-93. doi: 10.1152/jn.1999.81.2.479.
Reduction of the threshold of cardiovascular and neuronal responses to facial and intracranial stimulation reflects central sensitization and cutaneous allodynia in a rat model of migraine. Current theories propose that migraine pain is caused by chemical activation of meningeal perivascular fibers. We previously found that chemical irritation of the dura causes trigeminovascular fibers innervating the dura and central trigeminal neurons receiving convergent input from the dura and skin to respond to low-intensity mechanical and thermal stimuli that previously induced minimal or no responses. One conclusion of these studies was that when low- and high-intensity stimuli induce responses of similar magnitude in nociceptive neurons, low-intensity stimuli must be as painful as the high-intensity stimuli. The present study investigates in anesthetized rats the significance of the changes in the responses of central trigeminal neurons (i.e., in nucleus caudalis) by correlating them with the occurrence and type of the simultaneously recorded cardiovascular responses. Before chemical stimulation of the dura, simultaneous increases in neuronal firing rates and blood pressure were induced by dural indentation with forces >/= 2.35 g and by noxious cutaneous stimuli such as pinching the skin and warming > 46 degrees C. After chemical stimulation, similar neuronal responses and blood pressure increases were evoked by much smaller forces for dural indentation and by innocuous cutaneous stimuli such as brushing the skin and warming it to >/= 43 degrees C. The onsets of neuronal responses preceded the onsets of depressor responses by 1.7 s and pressor responses by 4.0 s. The duration of neuronal responses was 15 s, whereas the duration of depressor responses was shorter (5.8 s) and pressor responses longer (22.7 s) than the neuronal responses. We conclude that the facilitated cardiovascular and central trigeminal neuronal responses to innocuous stimulation of the skin indicate that when dural stimulation induces central sensitization, innocuous stimuli are as nociceptive as noxious stimuli had been before dural stimulation and that a similar process might occur during the development of cutaneous allodynia during migraine.
在偏头痛大鼠模型中，心血管和神经元对面部及颅内刺激反应阈值的降低反映了中枢敏化和皮肤异常性疼痛。目前的理论认为偏头痛疼痛是由脑膜血管周围纤维的化学激活引起的。我们之前发现，硬脑膜的化学刺激会导致支配硬脑膜的三叉神经血管纤维以及接收来自硬脑膜和皮肤汇聚输入的中枢三叉神经元对低强度机械和热刺激产生反应，而这些刺激之前只会引起最小反应或无反应。这些研究的一个结论是，当低强度和高强度刺激在伤害性神经元中引起相似幅度的反应时，低强度刺激必定与高强度刺激一样疼痛。本研究在麻醉大鼠中通过将中枢三叉神经元（即尾状核）反应的变化与同时记录的心血管反应的发生及类型相关联，来探究这些变化的意义。在硬脑膜化学刺激之前，用≥2.35 g的力进行硬脑膜压痕以及有害皮肤刺激（如捏皮肤和加热至>46℃）会同时引起神经元放电率和血压升高。化学刺激后，用小得多的力进行硬脑膜压痕以及无害皮肤刺激（如刷皮肤和加热至≥43℃）就能引起相似的神经元反应和血压升高。神经元反应的起始比降压反应的起始提前1.7秒，比升压反应的起始提前4.0秒。神经元反应的持续时间为15秒，而降压反应的持续时间较短（5.8秒），升压反应的持续时间比神经元反应长（22.7秒）。我们得出结论，心血管和中枢三叉神经元对皮肤无害刺激的易化反应表明，当硬脑膜刺激诱导中枢敏化时，无害刺激与硬脑膜刺激前的有害刺激一样具有伤害性，并且在偏头痛期间皮肤异常性疼痛的发展过程中可能会发生类似的过程。
