Guang-Xia Shi

Factors contributing to therapeutic effects evaluated in acupuncture clinical trials

Acupuncture treatment has been widely used for many conditions, while results of the increasing numbers of randomized trials and systematic reviews remain controversial. Acupuncture is a complex intervention of both specific and non-specific factors associated with therapeutic benefit. Apart from needle insertion, issues such as needling sensation, psychological factors, acupoint specificity, acupuncture manipulation, and needle duration also have relevant influences on the therapeutic effects of acupuncture. Taking these factors into consideration would have considerable implications for the design and interpretation of clinical trials.

Characterization of Deqi Sensation and Acupuncture Effect

Acupuncture stimulation elicits deqi, a composite of unique sensations. According to traditional Chinese medicine (TCM), deqi experienced by patients is often described as suan (aching or soreness), ma (numbness or tingling), zhang (fullness, distention, or pressure), and zhong (heaviness) and is felt by the acupuncturists (needle grasping) as tense, tight, and full. It is believed that deqi may be an important variable in the studies of the mechanism and efficacy of acupuncture treatment. In recent years, great efforts have been made to understand deqi, which include a couple of questionnaires to qualify and quantify deqi sensations, neuroimaging studies of deqi and acupuncture, physiological mechanisms of deqi, and the relation between deqi and clinical efficacy. However, many problems need to be resolved, and more researches are required to be made in the future.

Immediate Analgesia Effect of Single Point Acupuncture in Primary Dysmenorrhea: A Randomized Controlled Trial

BACKGROUND Acupuncture is often used for primary dysmenorrhea. OBJECTIVE To assess the efficacy of a single point of acupuncture in the management of primary dysmenorrhea compared with sham acupuncture and no acupuncture. METHODOLOGY Patients with primary dysmenorrhea were randomly assigned to acupoint group (n=50), unrelated acupoint group (n=50), nonacupoint group (n=46), or no acupuncture group (n=48). Acupuncture and sham acupuncture were administered once-daily for 3 days with electro-acupuncture at Sanyinjiao (SP6) that was specifically designed to treat primary dysmenorrhea, or an unrelated acupoint (Xuanzhong, GB39), or nonacupoint location. The primary outcome was pain intensity as measured by a 100-mm visual analog scale (VAS) at baseline; 5, 10, 30, and 60 minutes following the start of the first intervention. Cox retrospective symptom scale (RSS), verbal rating scale (VRS), pain total time, and proportion of participants using analgesics were also recorded during three menstrual cycles. RESULTS The primary comparison of VAS scores demonstrated that patients receiving acupuncture (-15.56 mm, 95% CI -22.16 to -8.95, P<0.001), unrelated acupoint (-18.14 mm, 95% CI -24.81 to -11.47, P<0.001), and nonacupoint (-10.96 mm, 95% CI -17.62 to -4.30, P=0.001) treatment presented significant improvements compared with no acupuncture group. There were no significant differences among the four groups with respect to secondary outcomes. CONCLUSION Acupuncture was better than no acupuncture for relieving the pain of dysmenorrhea following a single point of acupuncture, but no differences were detected between acupoint acupuncture and unrelated acupoint acupuncture, acupoint acupuncture and nonacupoint acupuncture.

Acupuncture Effect and Central Autonomic Regulation

Acupuncture is a therapeutic technique and part of traditional Chinese medicine (TCM). Acupuncture has clinical efficacy on various autonomic nerve-related disorders, such as cardiovascular diseases, epilepsy, anxiety and nervousness, circadian rhythm disorders, polycystic ovary syndrome (PCOS) and subfertility. An increasing number of studies have demonstrated that acupuncture can control autonomic nerve system (ANS) functions including blood pressure, pupil size, skin conductance, skin temperature, muscle sympathetic nerve activities, heart rate and/or pulse rate, and heart rate variability. Emerging evidence indicates that acupuncture treatment not only activates distinct brain regions in different kinds of diseases caused by imbalance between the sympathetic and parasympathetic activities, but also modulates adaptive neurotransmitter in related brain regions to alleviate autonomic response. This review focused on the central mechanism of acupuncture in modulating various autonomic responses, which might provide neurobiological foundations for acupuncture effects.

Effects of Acupuncture at Sanyinjiao (SP6) on Prostaglandin Levels in Primary Dysmenorrhea Patients

ObjectiveTo explore the physiologic mechanism of immediate analgesic effect of acupuncture in primary dysmenorrhea patients. MethodsForty primary dysmenorrhea patients were randomized into the Sanyinjiao (SP6) acupuncture group, Xuanzhong (GB39) control group, nonacupoint control group, or no acupuncture group. Patients in the 3 acupuncture groups were treated with electroacupuncture at assigned points lasting 30 minutes, whereas patients in no acupuncture group did not receive any acupuncture intervention. Before and after acupuncture, visual analogue scale (VAS) scores were recorded and blood samples were taken for the measurement of the plasma levels of 4 principal prostaglandins (PGE2, PGF2a, TXB2, and 6-keto PGF1a). ResultsThe VAS scores for pain intensity significant decreased in patients who received acupuncture compared with those had no acupuncture intervention. However, there were no significant differences among patients in the 3 acupuncture groups after acupuncture. In addition, no statistically significant differences were observed in the plasma PGE2, PGF2a, TXB2, or 6-keto PGF1a levels and the ratios of PGF2a/PGE2 , and TXB2/6-keto PGF1a after acupuncture at SP6. ConclusionsThe immediate analgesic effect of SP6 might not be mediated by changes in the prostaglandin levels.

Hippocampal cAMP/PKA/CREB is required for neuroprotective effect of acupuncture.

Acupuncture has beneficial effects in vascular dementia (VaD) patients. The underlying mechanism, however, remains unknown. The present study was designed to investigate whether the cAMP/PKA/CREB cascade is involved in the mechanism of acupuncture in cerebral multi-infarction rats. In this study, cerebral multi-infarction was modeled in adult Wistar rats by homologous blood clot emboli. After a two-week acupuncture treatment at Zusanli (ST36), hippocampal-dependent memory was tested by employing a radial arm maze test. The hippocampus was isolated for analyses of cAMP concentration, phosphodiesterase (PDE) activity and CREB/pCREB and ERK/pERK expressions. The Morris water maze (MWM) task and CREB phosphorylation were evaluated in the presence of PKA-selective peptide inhibitor (H89). The radial arm maze test results demonstrated that acupuncture treatment at ST36 reversed hippocampal-dependent memory in impaired animals. Compared to those of the impaired group, cAMP concentration, PKA activity and pCREB and pERK expressions were increased following acupuncture therapy. Finally, the blockade of PKA reversed the increase in CREB phosphorylation and the improvement in recognitive function induced by acupuncture treatment. These results suggest that acupuncture could improve hippocampus function by modulating the cAMP/PKA/CREB signaling pathway, which represents a molecular mechanism of acupuncture for recognitive function in cerebral multi-infarction rats.

Acupuncture ameliorates cognitive impairment and hippocampus neuronal loss in experimental vascular dementia through Nrf2-mediated antioxidant response.

Emerging evidence suggests acupuncture could exert neuroprotection in the vascular dementia via anti-oxidative effects. However, the involvement of Nrf2, a master regulator of antioxidant defense, in acupuncture-induced neuroprotection in vascular dementia remains undetermined. The goal of our study was to investigate the contribution of Nrf2 in acupuncture and its effects on vascular dementia. Morris water maze and Nissl staining were used to assess the effect of acupuncture on cognitive function and hippocampal neurodegeneration in experimental vascular dementia. The distribution of Nrf2 in neurons in hippocampus, the protein expression of Nrf2 in both cytosol and nucleus, and the protein and mRNA levels of its downstream target genes NQO1 and HO-1 were detected by double immunofluorescent staining, Western blotting and realtime PCR analysis respectively. Cognitive function and microglia activation were measured in both wild-type and Nrf2 gene knockout mice after acupuncture treatment. We found that acupuncture could remarkably reverse the cognitive deficits, neuron cell loss, reactive oxygen species production, and decreased cerebral blood flow. It was notable that acupuncture enhanced nuclear translocation of Nrf2 in neurons and up-regulate the protein and mRNA levels of Nrf2 and its target genes HO-1 and NQO1. Moreover, acupuncture could significantly down-regulated the over-activation of microglia after common carotid artery occlusion surgery. However, the reversed cognitive deficits, neuron cell loss and microglia activation by acupuncture were abolished in Nrf2 gene knockout mice. In conclusion, these findings provide evidence that the neuroprotection of acupuncture in models of vascular dementia was via the Nrf2 activation and Nrf2-dependent microglia activation.

Acupuncture elicits neuroprotective effect by inhibiting NAPDH oxidase-mediated reactive oxygen species production in cerebral ischaemia.

In the current study, we aimed to investigate whether NADPH oxidase, a major ROS-producing enzyme, was involved in the antioxidant effect of acupuncture on cognitive impairment after cerebral ischaemia. The cognitive function, infract size, neuron cell loss, level of superoxide anion and expression of NADPH oxidase subunit in hippocampus of two-vessel occlusion (2VO) rats were determined after 2-week acupuncture. Furthermore, the cognitive function and production of O2− were determined in the presence and absence of NADPH oxidase agonist (TBCA) and antagonist (Apocynin). The effect of acupuncture on cognitive function after cerebral ischaemia in gp91phox-KO mice was evaluated by Morris water maze. Acupuncture reduced infarct size, attenuated overproduction of O2−, and reversed consequential cognitive impairment and neuron cell loss in 2VO rats. The elevations of gp91phox and p47phox after 2VO were significantly decreased after acupuncture treatment. However, no differences of gp91phox mRNA were found among any experimental groups. Furthermore, these beneficial effects were reversed by TBCA, whereas apocynin mimicked the effect of acupuncture by improving cognitive function and decreasing O2− generation. Acupuncture failed to improve the memory impairment in gp91phox KO mice. Full function of the NADPH oxidase enzyme plays an important role in neuroprotective effects against cognitive impairment via inhibition of NAPDH oxidase-mediated oxidative stress.

Effect of acupuncture on Deqi traits and pain intensity in primary dysmenorrhea: analysis of data from a larger randomized controlled trial

BackgroundDeqi is a central concept in traditional Chinese acupuncture. We performed a secondary analysis on data from a larger randomized controlled trial (RCT) in order to assess the effect of acupuncture on deqi traits and pain intensity in primary dysmenorrhea.MethodsA total of 60 primary dysmenorrhea patients were enrolled and randomly assigned to one of three treatment groups. Acupuncture was given at SP6, GB39 or nonacupoint. Subjective pain was measured by a 100-mm visual analogue scale (VAS) before and after acupuncture. The Massachusetts General Hospital acupuncture sensation scales (MASS) with minor modification was used to rate deqi sensations during acupuncture.ResultsThe results showed that VAS scores of pain after acupuncture were significantly decreased comparing to before acupuncture treatment in all three groups (P = 0.000). However, no significant differences were found among three groups at the beginning or end of acupuncture treatment (P = 0.928, P = 0.419).ConclusionsThere was no statistical difference among three groups in terms of intensity of deqi feeling. The types of sensation were similar across the groups with only minor differences among them.Trial registrationTrial registration number: Controlled-Trials.com ISRCTN24863192.

Biomarkers of Oxidative Stress in Vascular Dementia Patients

OBJECTIVE Little is known about the role of oxidative stress in the pathogenesis of vascular dementia (VaD). The aim of this study was to investigate the biomarkers of oxidative stress in urine, as reflected by 8-hydroxydeoxyguanosine (8-OHdG), 8-isoprostaglandin F(2a) (8-isoPGF(2a)) and nitrotyrosine (NT) levels, in a group of well characterized VaD patients and in two control groups of Vascular Not Demented (VaND) patients and health y subjects. METHODS Ninety-six subjects from the Tianjin municipality in China were recruited. Forty-six patients were in the VaD group, 24 patients with VaND and 26 persons with no signs of cognitive disorder were employed as control groups. Urinary 8-OHdG and 8-isoPGF(2a) was performed using enzyme-linked immunosorbent assay (ELISA), and urinary NT levels were measured by chemiluminescence detection. RESULTS Significantly higher urinary 8-OHdG levels were detected in VaD patients compared to VaND patients and healthy control subjects. In contrast, urinary 8-isoPGF(2a) levels were significantly lower in VaD patients compared with two control groups. For NT levels, no statistically significant differences were observed among the three groups. CONCLUSION Increased urinary 8-OHdG level was a potential marker of oxidative stress in VaD patients. Furthermore, it is also important to take into account potential confounders in order to improve the identification of changes in the status of oxidative stress as related to VaD.