今天看到周耀旗博主写的“镇痛的堵和疏”一文，谈及针灸治好了他太太的脚痛，而此前曾用过镇痛药，但似乎不太管用，这说明中医药（包括针灸、推拿）在矫正身体不适或意外损伤（如头痛脑热、跌打损伤）方面有其独特疗效，尽管绝大多数人（包括针灸师）不一定能圆满地解释针灸治病的原理。

针灸镇痛的疗效应该是确切和得到广泛认同的，但恐怕很多人认为针灸镇痛仍然是治“标”不治“本”，因为它并不知道也没触及疼痛的根源。当我看到Nature Medicine上的一篇最新论文后，才知道针灸不仅仅能镇痛，而且还能抗炎，当然还有许多其他方面的奇效。就针灸消炎来说，由于很多“痛”都是由“炎”引起的，如类风湿性关节炎引起的关节红肿和疼痛，让我联想到针灸是否既能治标（缓解疼痛感觉）又能治本（消除引起疼痛的病因）呢？



最近，我有个针灸推拿专业毕业的学生打算做针灸加药治疗类风湿关节炎的实验研究，此前我们曾用青蒿素和雷帕霉素等药物治疗过本病。于是，学生查阅了大量中英文文献，我也陪着做了一点“功课”，很有收获。不过，我掌握的针灸中文文献还不多，而且只重点研读了有关针灸作用机理的英文文献，其中有3份文献分别阐明了针灸“镇痛”、“抗应激”和“消炎”的分子机制，现择要介绍如下。

针灸镇痛的分子机理

Goldman N, et al. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture. Nat Neurosci 2010, 13(7): 883-888.

此文为NIH Public Access，任何人可以从PubMed Central免费下载和阅读。

Abstract
    Acupuncture is an invasive procedure commonly used to relieve pain. Acupuncture is practiced worldwide, despite difficulties in reconciling its principles with evidence-based medicine. We found that adenosine, a neuromodulator with anti-nociceptive properties, was released during acupuncture in mice and that its anti-nociceptive actions required adenosine A1 receptor expression. Direct injection of an adenosine A1 receptor agonist replicated the analgesic effect of acupuncture. Inhibition of enzymes involved in adenosine degradation potentiated the acupuncture-elicited increase in adenosine, as well as its anti-nociceptive effect. These observations indicate that adenosine mediates the effects of acupuncture and that interfering with adenosine metabolism may prolong the clinical benefit of acupuncture.

小鼠中的实验表明，针灸可以诱导镇痛性神经调节剂——腺苷的分泌，而其发挥镇痛效果的前提是腺苷与腺苷A1受体结合。用腺苷A1受体拮抗剂注射小鼠，可以复制针灸的镇痛作用。用腺苷降解酶抑制剂注射小鼠，可以提高腺苷的含量，同时增强其镇痛效果。这个实验说明腺苷就是针灸镇痛作用的分子基础，腺苷分解越慢，其镇痛持续的时间就越长。

针灸抗应激的分子机理

Eshkevari L, et al. Acupuncture at ST36 prevents chronic stress-induced increases in neuropeptide Y in rat. Exp Bio Med 2012, 237:18-23.

该文的PDF版可以在google直接搜索到，请自行下载和阅读。

Abstract

Chronic stress, as seen in post-traumatic stress disorder, can exacerbate existing diseases. Electroacupuncture (EA) has been proposed to treat chronic stress, although information on its efficacy or mechanism(s) of action is limited. While many factors contribute to the chronic stress response, the sympathetic peptide, neuropeptide Y (NPY), has been shown to be elevated in chronic stress and is hypothesized to contribute to the physiological stress response. Our objective was to determine if EA at acupuncture point stomach 36 (ST36) is effective in mitigating cold stress-induced increase in NPY in rats. Both pretreatment and concomitant treatment with EA ST36 effectively suppressed peripheral and central NPY after 14 d of cold stress (P, 0.05). The effect was specific, as NPY in Sham-EA rats was not different than observed in stress-only rats. Additionally, the effect of
EA ST36 was long-lasting, as NPY levels remained suppressed despite early cessation of EA ST36, while exposure to cold stress was continued. In the paraventricular nucleus (PVN), it was notable that changes in NPY mirrored plasma NPY levels, and that the significant elevation in PVN Y1 receptor observed with stress was also prevented with EA ST36. The findings indicate that EA ST36 is effective in preventing one of the sympathetic pathways stimulated during chronic stress, and thus may be a useful adjunct therapy in stress-related disorders.



该文用大鼠所做实验的结果表明，除镇痛外，针灸还能缓解长时间寒冷诱发的生理应激反应。冷应激的分子基础就是大量分泌交感神经肽——神经肽Y（NPY），而针灸足三里就能抑制NPY的分泌，同时也会阻止下丘脑室旁核（PVN）Y1受体的增加。这项研究表明在足三里处针灸能阻断慢性应激刺激的交感神经通路，可用于应激相关疾病的辅助治疗。

针灸抗炎的分子机理

Torres-Rosas R, et al. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med 2014, 20: 291-295

这篇Nature系列文章目前还不能免费下载全文，但从孙学军老师的博文针灸作用机制新解释可以找到这篇文章。

Abstract

Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings. Neuronal networks represent physiological mechanisms, selected by evolution to control inflammation, that can be exploited for the treatment of inflammatory and infectious disorders. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing vagal activation of aromatic
l-amino acid decarboxylase, leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized mice mimic clinical adrenal insufficiency4, increase the susceptibility to sepsis and prevent the anti-inflammatory effects of electroacupuncture. Dopamine inhibits cytokine production via dopamine type 1 (D1) receptors. D1 receptor agonists suppress systemic inflammation and rescue mice with adrenal insufficiency from polymicrobial peritonitis. Our results suggest a new anti-inflammatory mechanism mediated by the sciatic and vagus nerves that modulates the production of catecholamines in the adrenal glands. From a pharmacological perspective, the effects of selective dopamine agonists mimic the anti-inflammatory effects of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders.  

这篇文章描述了针灸消炎的新发现，将使针灸在未来疾病的治疗上产生“革命性”影响，它不再仅仅是镇痛那么简单，还可以用来对抗感染引起的炎症，尤其是抗药性细菌感染。研究表明，对坐骨神经及迷走神经的电针刺激，可以激活肾上腺髓质中的芳香族氨基酸脱羧酶，从而促进多巴胺的产生，而多巴胺可经由多巴胺1型（D1）受体抑制促炎细胞因子的合成，从而缓解全身炎症。下图数据显示，经电针刺激后，脂多糖诱导的肿瘤坏死因子（TNF）、单核细胞趋化蛋白1（MCP-1）、白细胞介素6（IL-6）和干扰素γ（IFN-γ）等促炎细胞因子的血清浓度明显降低，而且在6小时内未见升高。

为什么针灸能抑制促炎细胞因子的分泌呢？作者的观点是针灸通过多巴胺起抗炎作用。可是，我们在小鼠中所做的初步电针实验发现了一种有关免疫抑制的奇特现象，目前正在重复这个实验结果。假如这种现象可以重复出现，也许我们可以为针灸抑制促炎细胞因子合成的机理提供另一种解释。

话说回来，若周耀旗博主太太的脚痛真是由于某种炎症引起的，那么针灸的抗炎止痛作用就是“有的放矢”了，但也不能排除脚痛就是久站引起的疲劳性损伤。对此，根据针灸止痛的持续时间是否可以加以区分呢？比如，一次性治愈就是疲劳性损伤，而必须多次治疗就是炎症性疼痛。我的这个判断是不是靠谱，请行家们不吝斧正。

小小新娘花（云菲菲） 

花蝴蝶（田丰）