Nitric oxide signaling molecules in acupoints: Toward mechanisms of acupuncture

Abstract

Recent clinical trial studies have demonstrated that the effects of acupuncture on pain improvement are small and no difference between acupuncture points (acupoints) and non-points. Whether acupuncture needles must be inserted in specific points depends on whether acupoint specificity exists that is still not resolved, and is now urgent. Previous anatomical studies have demonstrated that acupoints exist higher number of nerve fibers/trunks, blood vessels, hair follicles, and sweat glands as well as density of the gap junction. Recent evidence shows that nitric oxide (NO) level is elevated in the acupoints/meridians and is associated with an enhanced expression of NO synthase endowed with transient receptor potential vanilloid type-1. There is growing evidence from international groups showing that acupuncture induces NO-mediated vasodilatation, which increases local blood flow and allows for a flush of algesic or sensitizing substances, leading to pain relief. Previous studies, using a novel biocapture system, have demonstrated that NOx- (total nitrite and nitrate) and cGMP concentrations are consistently increased over skin acupuncture points (acupoints) compared to non-meridian control regions (NMCR) in humans. Dermal microdialysis in humans showed that NO-cGMP releases in the subcutaneous tissue of acupoint are higher than those in NMCR and increased by electroacupuncture (EA). Recent studies have demonstrated that low-frequency electrical stimulation and manual acupuncture with low stimulating force and rate produce an elevation of NO release predominantly over acupoints. In contrast, NO levels over the areas of the skin regions are moderately reduced by high-frequency EA stimulation. The reinforcement methods induce an elevation of vasodilator (NO) release over skin, which contribute to local warmness and beneficial effects of EA including pain relief. Although the specificity of acupoints and monitoring the quantitative response to acupuncture require further investigation, the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of NO signaling molecules, and stimulus-evoked NO release is also with a higher level at acupoints. Results suggest that NO signaling molecules contribute to the specificity of acupoints, and selecting well-trained acupuncturetists for using correct acupoints and appropriate parameters should improve acupuncture clinical trial studies.

Electroacupuncture at Zusanli and at Neiguan characterized point specificity in the brain by metabolomic analysis

“…l-arginine induces vasodilation, and its long-term oral administration can alleviate the clinical symptoms of cardiovascular disorders 26 . NO levels are elevated in acupoints, inducing vasodilation and leading to an increase in local blood flow and also contributes to the specificity of acupoints 27 . The change of arginine level in these results partly support to explain of specificity of acupoints.…”

In Vivo Visualization of the Pericardium Meridian with Fluorescent Dyes

“…As early as the 1950s, points and meridians were identified as localized sites with increased electrical conductivity, reduced resistance, and increased capacitance [1,10,11]. Furthermore, these electrically distinct points were associated with unique histological, functional properties such as increased gap junctions [12,13], nNOS expression [12,14], and subcutaneous collagenous bands [15]. e third hypothesis, which has garnered more interest recently, is the notion that acupoints are sites with increased pressure sensitization, which are further accentuated by the presence of clinical pathology [16][17][18][19].…”

Spinal manipulation and perineural electrical dry needling in patients with cervicogenic headache: a multicenter randomized clinical trial

“…increased plasma βendorphin levels-and significantly reducing plasma cortisol levels, [72] electrical dry needling may enhance intra and extra neural microcirculation via local neovascularization and vasodilation through autonomic reflexes and nitric oxide release. [73,74] Moreover, electroacupuncture has been found to reduce the expression of proinflammatory cytokines (i.e., interleukin-1 β and tumor necrosis factor-α) in the synovia of joints [75] and inflamed soft-tissue, [76,77] and block the systemic release of inflammatory factors in the periaqueductal gray area of the brain stem. [78] This may lead to decreased inflammation of the densely innervated periarticular connective tissue of the upper cervical articulations, suboccipital muscles, and the greater occipital nerve, lesser occipital nerve, third occipital nerve and great auricular nerve, [75][76][77][78] which is most frequently reported by patients as the region of the origin of symptoms before they proceed unilaterally into the posterior occiput…”