丘脑中央下核和腹外侧眶皮层在针刺镇痛和痛觉调制中的整合作用

近年来 ,我们根据以往解剖学和电生理学的研究 ,提出并证明了一个假设 ,即 :丘脑中央下核(Ｓｍ)和腹外侧眶皮层 (ＶＬＯ)在整合伤害性信息的过程中 ,不仅参与痛觉感受 ,也参与痛觉调制。Ｓｍ ＶＬＯ ＰＡＧ构成一个痛觉调制通路 ,通过激活脑干下行抑制系统在脊髓和三叉水平抑制伤害感受性传递。该通路在针刺兴奋细纤维产生的镇痛中起重要作用。研究结果如下 :①电解损毁双侧Ｓｍ易化辐射热诱发的大鼠甩尾 (ＴＦ)反射 ,ＴＦ反射潜伏期 (ＴＦＬ)明显缩短。如果Ｓｍ是一个单纯的痛觉感受中枢 ,损毁它应当得到相反的结果。提示Ｓｍ参与痛觉调制 …

The Integrative Action of Thalamic Nucleus Submedius and Ventrolateral Orbital Cortex in Acupuncture Modulation on Nociceptive Stimulation

It was suggested that the nucleus submedius (Sm) in the medial thalamus and the ventrolateral orbital cortex (VLO) in the prefrontal cortex were involved not only in nociception, but also in modulation of nociception. The Sm VLO PAG may constitute a pathway responsble for nociceptive modulation. Activation of this pathway depresses the nociceptive inputs at the spinal and trigeminal levels via the brainstem descending inhibitory system. This pathway may play an important role in analgesia produced by acupuncture evoked inputs from the small afferent fibers. For proving this hypothesis, a series of studies were performed in our laboratory.① Results of the present study revealed that bilateral electrolytic lesions of the Sm facilitated the radiant heat evoked tail flick (TF) reflex, with the latency of the TF reflex shortening in the rat lightly anesthetized with pentobarbital. If the Sm is purely a nociceptive center, the contrary result should be obtained. Therefore, this result suggests that Sm may be involved in nociceptive modulation, and may exert a tonic descending inhibitory influence on nociceptive transmission. Further investigations indicated that unilateral electrical stimulation of Sm or microinjection of glutamate into Sm significantly depressed the TF reflex, the jaw opening reflex (JOR), as well as the nociceptive responses of neurons in the spinal cord dorsal horn. All these effects were intensity (or dose) dependent and location specific. Moreover, the Sm evoked antinociception could be markedly reduced or eliminated by electrolytic lesion of ipsilateral VLO or bilateral lesions of ventrolateral or lateral parts of PAG, or by microinjection of GABA into VLO or PAG. Similarly, electrical or chemical activation of VLO also produced antinociception, and this effect was eliminated by lesion or depression of the PAG. These facts suggest that the antinociception produced by activation of Sm is mediated by VLO, leading to activation of the PAG brainstem descending inhibitory system and depression of the nociceptive inputs at the spinal and trigeminal levels. The Sm may be the only modulative center of nociception in the ventromedial thalamus, while the VLO may be the higher center of the pathway of nociceptive modulation consisting of Sm VLO PAG. Recent studies revealed that the Sm VLO PAG pathway may be also involved in modulation of the inflammatory hyperalgesia elicited by formalin. Electrical stimulation of the Sm could depresse the tonic nociceptive responses (agitation) elicited by subcutaneous injection of formalin into rat sole. Electrophysiological studies have demonstrated that on cell and off cell involved in the descending inhibitory modulation of nociception also exist in the Sm, suggesting that interaction of the two types of neurons in Sm may be the neuronal mechanisms. ② It was found that acupuncture manipulation and electroacupuncture (EA) stimulation with high intensity for activation of the fine afferent fibers in "acupoints" could activate the neurons in Sm, and markedly depressed the rat TF reflex and the nociceptive responses of neurons in the spinal cord dorsal horn. The antinociceptive effects produced by high intensity EA could be significantly attenuated by bilateral electrolytic lesions of Sm, or by microinjection of local anesthetic lidocaine into Sm. However, EA stimulation with low intensity for exciting only the large afferent fibers could not activate the Sm neurons, and the antinociceptive effects produced by such EA stimulation could not be affected by Sm or VLO lesions or application of lidocaine, but could be attenuated significantly by lidocaine application to the anterior pretectal nucleus (AptN). These facts suggest that antinociception produced by high intensity EA stimulation of "acupoints" is mediated by Sm VLO PAG system, but that produced by low intensity EA stimulation is not. This study also indicates that the acupuncture manipulation and high intensity EA are likely to act as noxious stimulation to elicit antinociception. ③ Microinjection of morp