Electroacupuncture Exerts Analgesic Effects by Restoring Hyperactivity via Cannabinoid Type 1 Receptors in the Anterior Cingulate Cortex in Chronic Inflammatory Pain.

As one of the commonly used therapies for pain-related diseases in clinical practice, electroacupuncture (EA) has been proven to be effective. In chronic pain, neurons in the anterior cingulate cortex (ACC) have been reported to be hyperactive, while the mechanism by which cannabinoid type 1 receptors (CB1Rs) in the ACC are involved in EA-mediated analgesic mechanisms remains to be elucidated. In this study, we investigated the potential central mechanism of EA analgesia. A combination of techniques was used to detect the expression and function of CB1R, including quantitative real-time PCR (q-PCR), western blot (WB), immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), and in vivo multichannel optical fibre recording, and neuronal activity was examined by in vivo two-photon imaging and in vivo electrophysiological recording. We found that the hyperactivity of pyramidal neurons in the ACC during chronic inflammatory pain is associated with impairment of the endocannabinoid system. EA at the Zusanli acupoint (ST36) can reduce the hyperactivity of pyramidal neurons and exert analgesic effects by increasing the endocannabinoid ligands anandamide (AEA), 2-arachidonoylglycerol (2-AG) and CB1R. More importantly, CB1R in the ACC is one of the necessary conditions for the EA-mediated analgesia effect, which may be related to the negative regulation of the N-methyl-D-aspartate receptor (NMDAR) by the activation of CB1R downregulating NR1 subunits of NMDAR (NR1) via histidine triad nucleotide-binding protein 1 (HINT1). Our study suggested that the endocannabinoid system in the ACC plays an important role in acupuncture analgesia and provides evidence for a central mechanism of EA-mediated analgesia.

The Role of Perineuronal Nets in the Contralateral Hemisphere in the Electroacupuncture-Mediated Rehabilitation of Poststroke Dysphagia Mice.

Acupuncture at Lianquan (CV23) acupoint has been shown to improve swallowing function in poststroke dysphagia (PSD). This improvement is supposed to be associated with the regulation of neuronal activity in the contralateral primary motor cortex (M1), while the underlying mechanism still needs to be elucidated. Perineuronal nets (PNNs) are well-known to be involved in the regulation of neuronal activity. Thus, we here aimed to detect the role of PNNs in the contralateral M1 hemisphere in the electroacupuncture (EA)-mediated effect in male mice. The results were obtained from a combination of methods, including in vitro slice electrophysiological recording, in vivo electrophysiological recording, and immunofluorescent staining in male mice. These results showed a decrease of the excitatory postsynaptic currents (sEPSCs) and no alteration of the inhibitory postsynaptic currents (sIPSCs) in the GABAergic neurons and the tonic inhibition in the excitatory neurons in the contralateral M1 after stroke induction, and EA recovered the impaired sEPSCs in the GABAergic neurons. We further found that the effect of EA-induced increase of c-Fos expression, enhancement of spike firing, potentiation of sEPSCs in the excitatory neurons, and improvement of swallowing function were all blocked by the removal of PNNs in the contralateral M1. In conclusion, the PNNs in the contralateral M1 was suggested to be participated in stroke pathogenesis and might be associated with the EA-mediated swallowing function rehabilitation of PSD in male mice. Our study provides insight into how PNNs might be involved in the mechanism of EA treatment for stroke rehabilitation.

Electroacupuncture improves swallowing function in a post-stroke dysphagia mouse model by activating the motor cortex inputs to the nucleus tractus solitarii through the parabrachial nuclei.

As a traditional medical therapy, stimulation at the Lianquan (CV23) acupoint, located at the depression superior to the hyoid bone, has been shown to be beneficial in dysphagia. However, little is known about the neurological mechanism by which this peripheral stimulation approach treats for dysphagia. Here, we first identified a cluster of excitatory neurons in layer 5 (L5) of the primary motor cortex (M1) that can regulate swallowing function in male mice by modulating mylohyoid activity. Moreover, we found that focal ischemia in the M1 mimicked the post-stroke dysphagia (PSD) pathology, as indicated by impaired water consumption and electromyographic responses in the mylohyoid. This dysfunction could be rescued by electroacupuncture (EA) stimulation at the CV23 acupoint (EA-CV23) in a manner dependent on the excitatory neurons in the contralateral M1 L5. Furthermore, neuronal activation in both the parabrachial nuclei (PBN) and nucleus tractus solitarii (NTS), which was modulated by the M1, was required for the ability of EA-CV23 treatment to improve swallowing function in male PSD model mice. Together, these results uncover the importance of the M1-PBN-NTS neural circuit in driving the protective effect of EA-CV23 against swallowing dysfunction and thus reveal a potential strategy for dysphagia intervention.

Excitatory neurons in paraventricular hypothalamus contributed to the mechanism underlying acupuncture regulating the swallowing function.

Paraventricular hypothalamus (PVH) is demonstrated to regulate stress, feeding behaviors, and other related homeostatic processes. However, no direct evidence has been investigated for the role of PVH in swallowing function. Acupuncture therapy at Lianquan (CV23) acupoint has been reported to improve the swallowing function in clinical trials, but its underlying mechanism still needs to be uncovered. Thus, we aimed to explore whether PVH involved the acupuncture mediated regulating swallowing function. Chemogenetics, electromyography (EMG) recording, and immunofluorescence staining methods were combined to demonstrate that neurons in PVH could be activated by electroacupuncture (EA) stimulation at CV23, and this neuronal cluster was represented as excitatory neurons. Furthermore, we mapped both the inputs and outputs of PVH neurons using viral tracing. The neurons in PVH projected with the brain regions, including parabrachial nucleus (PBN) and the solitary tract nucleus (NTS), which both participated in the swallowing process. The EA function regulating the swallowing was attenuated after inhibiting the neurons in PVH in the post stroke dysphagia. In conclusion, this study suggested that EA at CV23 could regulate swallowing function involving the excitatory neurons in PVH.

Contralateral S1 function is involved in electroacupuncture treatment-mediated recovery after focal unilateral M1 infarction.

Acupuncture at acupoints Baihui (GV20) and Dazhui (GV14) has been shown to promote functional recovery after stroke. However, the contribution of the contralateral primary sensory cortex (S1) to recovery remains unclear. In this study, unilateral local ischemic infarction of the primary motor cortex (M1) was induced by photothrombosis in a mouse model. Electroacupuncture (EA) was subsequently performed at acupoints GV20 and GV14 and neuronal activity and functional connectivity of contralateral S1 and M1 were detected using in vivo and in vitro electrophysiological recording techniques. Our results showed that blood perfusion and neuronal interaction between contralateral M1 and S1 is impaired after unilateral M1 infarction. Intrinsic neuronal excitability and activity were also disturbed, which was rescued by EA. Furthermore, the effectiveness of EA treatment was inhibited after virus-mediated neuronal ablation of the contralateral S1. We conclude that neuronal activity of the contralateral S1 is important for EA-mediated recovery after focal M1 infarction. Our study provides insight into how the S1-M1 circuit might be involved in the mechanism of EA treatment of unilateral cerebral infarction. The animal experiments were approved by the Committee for Care and Use of Research Animals of Guangzhou University of Chinese Medicine (approval No. 20200407009) April 7, 2020.

Tuina for cervical vertigo: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Cervical vertigo (CV), one of the most common causes of vertigo, makes patients feel dizzy, which seriously affects patients' lives. As a traditional Chinese bone-setting manipulation, Tuina is widely used to treat CV. This article aims to evaluate the effectiveness and safety of Tuina for CV. METHODS: Nine databases were searched. Methodological quality was evaluated with the Cochrane Collaboration's tool. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was applied to determine confidence in the effect estimates. Stata 12.0 software was used to carry out the meta-analysis, and a trial sequential analysis (TSA) was performed with TSA 0.9. RESULTS: Nine randomized controlled trials (RCTs) were included. Low-quality evidence suggested that Tuina showed a significantly higher effectiveness rate compared to massage therapy (risk ratio (RR) = 1.11, 95% confidence intervals (CI): 1.05 to 1.17, p < 0.0001) and cervical traction (RR = 1.37, 95% CI: 1.09 to 1.72, p = 0.007; I2 = 0%, p = 0.826). Two trials reported that Tuina was better than acupuncture (RR = 1.40, 95% CI: 1.07 to 1.83) or betahistine mesilate (RR = 1.17, 95% CI: 0.99 to 1.37) based on an improved effectiveness rate. Low-quality evidence showed that Tuina was superior to massage therapy in improving scores on the evaluation scale for cervical vertigo (ESCV) (weighted mean differences (WMD) = 2.52, 95% CI: 1.11 to 3.94, p < 0.0001). Adverse events were tolerable. TSA revealed that an improved effectiveness rate was indicated. CONCLUSION: Tuina might improve the effectiveness rate and ESCV scores in patients with CV. However, the level of all the available evidence was low, and larger-scale and well-designed RCTs should be encouraged.