温针治痛："非伤害性"热刺激镇痛作用及其机制研究

More recently, our series of studies conducted in humans and animals have provided novel findings showing that the endogenous descending modulation of pain is normally inactive or 'silent', but not tonic, and needs to be triggered by sufficient C-afferent input. However, the fact of lower triggering thresholds of descending facilitation compared with higher threshold of descending inhibition brings us the obstacle in initiating the descending inhibition alone without excitation of descending facilitation. More recently, we demonstrated that warm needle stimulation at temperature of 43 C selectively triggered the descending inhibition. Accordingly, the applicant hypothesizes here that non-painful stimulation which excites peripheral C-fibers may timely initiate the dendogenous descending control of pain, and might be a promsing way in effectively control of pain. Utilizing multi-disciplinary approaches including behavioral, electrophysiological (simultaneous recordings of spinal dorsal horn neurons activities and gastronemius EMG activities), immunohistochemical and molecular biology methods, from the systemic, cellular, and molecular levels, the current application will explore potential effects of 43 C warm needle stimulation applied onto the Zusanli acupoint on the preception of pain associated with thalamus mediated potential neurobiological mechanisms. Exploration of non-painful heating-needle stimulation may provide novel evidence in moxibustion induced analgesia by means of initiation and enhancement of the descending inhibition, but not the facilitation, within tranditional Chinese medicine area.

课题组近期系列研究提示生理状态下痛觉内源性调控作用：易化和抑制，是处于静态或相对不活动的，需要外周足量的C-纤维传入激活。然而，较低的下行易化激活阈和较高的下行抑制激活阈为仅仅激活下行抑制而不激惹下行易化作用，从而达到有效治痛带来了困难。课题组近期实验证实43 °C温针刺激能够选择性激活痛觉内源性下行抑制作用。基于此，申请者提出：在"不引起明显痛感"的前提下选择性兴奋并增强C-纤维传入，及时激活内源性镇痛系统，可能是痛觉治疗的有效手段。本课题运用申请者创建的同步记录电生理记录模型（脊髓背角WDR神经元-腓肠肌肌电活动），联合行为学、免疫组化及分子生物学等多方法，从整体、细胞和分子角度在多层面上深入探索和验证"足三里"穴位43 °C温针治痛的丘脑神经生物学调控作用及机制。在不兴奋下行易化作用前提下，通过"不引起明显痛感"的温热刺激达到启动和增强下行抑制作用，为中医灸法治痛提供科研新资料。

如何有效治痛，已成为痛觉研究领域内亟待解决的关键科学问题。与药物镇痛相比，灸法治痛具有起效快，创伤小，且副作用低等优点。然而灸法治痛仍面临许多关键科学问题，如适宜温度和施治时间，需要解决。本课题对中医灸法的治痛作用及机制给予了细致探索。通过紧密围绕课题组创新性提出的丘脑介导的静态或“相对不活动”的痛觉内源性特异性双调控作用（易化和抑制）这一关键科学论点，深入探索了伤害性热刺激和“不引起明显痛感”的温热刺激对痛觉内源性调控作用的可能影响，并揭示了相关的细胞及分子机制。课题组首次报道：在不激惹内源性易化作用的前提下，43°C温针能选择性地激活下行抑制作用，从而达到有效治痛目的。同时，丘脑介导的不同的神经药理学机制参与上述调控作用。本研究为中医灸法治痛提供科研新资料，具有重要的临床实用价值。.实验结果如下：(1) 行为学实验及免疫组化学实验：43°C温针刺激选择性激活下行抑制作用；46°C热针刺激既激活下行抑制作用，也激活下行易化作用，因此抵消一部分镇痛作用；与非穴位刺激相比，“足三里”穴位温针镇痛效果显著强于非穴位刺激；(2) 神经药理学机制：丘脑MD和VM核团内Opioid不同受体及TRPV1受体参与上述温针介导的痛觉调控作用；(3) 临床治疗学：温热针刺激具有时间总和和空间总和效应。长于30分钟的热针刺激并没有为临床治疗带来更强的镇痛作用；而短于15分钟的热针刺激通常也不易激活痛觉内源性抑制作用。较单针刺激而言，双针热刺激可以引起更强，且持续时间更长的镇痛作用，显示了其具有空间总和的特点。同时，温针穴位刺激具有“上病下治”和“左病右治”的临床治疗特点。