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Despite accumulating evidence of the clinical effectiveness of acupuncture, its mechanism remains largely unclear. We assume that molecular signaling around the acupuncture needled area is essential for initiating the effect of acupuncture. To determine possible bio-candidates involved in the mechanisms of acupuncture and investigate the role of such bio-candidates in the analgesic effects of acupuncture, we conducted 2 stepwise experiments. First, a genome-wide microarray of the isolated skin layer at the GB34-equivalent acupoint of C57BL/6 mice 1 hour after acupuncture found that a total of 236 genes had changed and that extracellular signal–regulated kinase (ERK) activation was the most prominent bio-candidate. Second, in mouse pain models using formalin and complete Freund adjuvant, we found that acupuncture attenuated the nociceptive behavior and the mechanical allodynia; these effects were blocked when ERK cascade was interrupted by the mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (MAPK) inhibitor U0126 (.8 μg/μL). Based on these results, we suggest that ERK phosphorylation following acupuncture needling is a biochemical hallmark initiating the effect of acupuncture including analgesia. Perspective This article presents the novel evidence of the local molecular signaling in acupuncture analgesia by demonstrating that ERK activation in the skin layer contributes to the analgesic effect of acupuncture in a mouse pain model. This work improves our understanding of the scientific basis underlying acupuncture analgesia.

BackgroundAnkle sprain is one of the most frequently encountered musculoskeletal injuries; however, the efficacy of acupuncture in treating ankle sprains remains uncertain. We therefore performed a systematic review to evaluate the evidence regarding acupuncture for ankle sprains.MethodsWe searched 15 data sources and two trial registries up to February 2012. Randomized controlled trials of acupuncture were included if they involved patients with ankle sprains and reported outcomes of symptom improvement, including pain. A Cochrane risk of bias assessment tool was used. Risk ratio (RR) or mean difference (MD) was calculated with 95% confidence intervals (CIs) in a random effects model. Subgroup analyses were performed based on acupuncture type, grade of sprain, and control type. Sensitivity analyses were also performed with respect to risk of bias, sample size, and outcomes reported.ResultsSeventeen trials involving 1820 participants were included. Trial quality was generally poor, with just three reporting adequate methods of randomization and only one a method of allocation concealment. Significantly more participants in acupuncture groups reported global symptom improvement compared with no acupuncture groups (RR of symptoms persisting with acupuncture = 0.56, 95% CI 0.42–0.77). However, this is probably an overestimate due to the heterogeneity (I2 = 51%) and high risk of bias of the included studies. Acupuncture as an add-on treatment also improved global symptoms compared with other treatments only, without significant variability (RR 0.61, 95% CI 0.51–0.73, I2 = 1%). The benefit of acupuncture remained significant when the analysis was limited to two studies with a low risk of bias. Acupuncture was more effective than various controls in relieving pain, facilitating return to normal activity, and promoting quality of life, but these analyses were based on only a small number of studies. Acupuncture did not appear to be associated with adverse events.ConclusionsGiven methodological shortcomings and the small number of high-quality primary studies, the available evidence is insufficient to recommend acupuncture as an evidence-based treatment option. This calls for further rigorous investigations.

This study first showed the behavioural benefits of novel combination therapy of l-dopa with acupuncture on Parkinson’s disease, and its underlying mechanisms within basal ganglia. The previous study reported that acupuncture may improve the motor function of a Parkinson’s disease (PD) mouse model by increasing the dopamine efflux and turnover ratio of dopamine. Hence, we hypothesised that combining l-dopa with acupuncture would have a behavioural benefit for those with PD. We performed unilateral injections of 6-OHDA into the striatum of C57Bl/6 mice to model hemi-Parkinsonian attributes. To test motor function and dyskinetic anomalies, we examined cylinder behaviour and abnormal involuntary movement (AIM), respectively. We found that (1) a 50% reduced dose of l-dopa (7.5 mg/kg) combined with acupuncture showed an improvement in motor function that was comparable to mice given the standard dose of l-dopa treatment (15 mg/kg) only, and that (2) the combination treatment (l-dopa +acupuncture) was significantly superior in reducing AIM scores when equivalent doses of l-dopa were used. The combination treatment also significantly reduces the abnormal increase of GABA contents in the substantia nigra compared to the standard l-dopa treatment. Furthermore, abnormal expression of FosB, the immediate early gene of l-dopa induced dyskinesia (LID), was mitigated in the striatum by the combination treatment. All of these results indicate that acupuncture enhances the benefits of l-dopa on motor function with reduced dose of l-dopa and alleviating LID by normalising neurochemical imbalance within the basal ganglia.