Electroacupuncture suppresses neuronal ferroptosis to relieve chronic neuropathic pain.

Growing evidence supports the analgesic efficacy of electroacupuncture (EA) in managing chronic neuropathic pain (NP) in both patients and NP models induced by peripheral nerve injury. However, the underlying mechanisms remain incompletely understood. Ferroptosis, a novel form of programmed cell death, has been found to be activated during NP development, while EA has shown potential in promoting neurological recovery following acute cerebral injury by targeting ferroptosis. In this study, to investigate the detailed mechanism underlying EA intervention on NP, male Sprague-Dawley rats with chronic constriction injury (CCI)-induced NP model received EA treatment at acupoints ST36 and GV20 for 14 days. Results demonstrated that EA effectively attenuated CCI-induced pain hypersensitivity and mitigated neuron damage and loss in the spinal cord of NP rats. Moreover, EA reversed the oxidative stress-mediated spinal ferroptosis phenotype by upregulating reduced expression of xCT, glutathione peroxidase 4 (GPX4), ferritin heavy chain (FTH1) and superoxide dismutase (SOD) levels, and downregulating increased expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), malondialdehyde levels and iron overload. Furthermore, EA increased the immunofluorescence co-staining of GPX4 in neurons cells of the spinal cord of CCI rats. Mechanistic analysis unveiled that the inhibition of antioxidant pathway of Nrf2 signalling via its specific inhibitor, ML385, significantly countered EA's protective effect against neuronal ferroptosis in NP rats while marginally diminishing its analgesic effect. These findings suggest that EA treatment at acupoints ST36 and GV20 may protect against NP by inhibiting neuronal ferroptosis in the spinal cord, partially through the activation of Nrf2 signalling.

Efficacy and safety of bloodletting puncture and cupping in postherpetic neuralgia: A systematic review and meta­analysis.

The present study aimed to evaluate the efficacy and safety of bloodletting puncture and cupping (BLP-C) in postherpetic neuralgia (PHN) and to provide guidance for clinical treatment. Randomized controlled trials (RCTs) of BLP-C therapy in PHN were systematically searched in eight databases from inception to September 2022. Literature screening, data extraction and quality assessment were performed by two independent researchers. Dichotomous and continuous variables were pooled using the risk ratio (RR) and weighted mean difference (WMD), respectively. A total of 13 studies involving 1,129 patients with PHN (571 in the experimental group and 558 in the control group) were included in the present meta-analysis. Overall efficacy (RR=1.21, 95% CI: 1.15 to 1.28, P<0.00001), VAS score (WMD=-1.10, 95% CI: -1.31 to -0.90, P<0.00001) and PSQI score (WMD=-2.42, 95% CI: -2.87 to -1.96, P<0.0001) were significantly different between the BLP-C group and Western medicine group. Furthermore, subgroup analysis demonstrated that BLP-C alone or combined with other traditional Chinese medicines was more effective than Western medicine in PHN. A total of four RCTs mentioned adverse reactions, most of which were in the Western medicine group and were relieved after treatment discontinuation. In conclusion, BLP-C is superior to Western medicine in relieving pain and improving the sleep quality of patients with PHN with a lower incidence of adverse effects.

Efficacy of Combining Traditional Chinese Manual Therapy (Tuina) and Specific Therapeutic Neck Exercise in Young Adults with Non-Specific Chronic Neck Pain: Study Protocol for a Randomized Controlled Trial.

Purpose: Non-specific chronic neck pain (NSCNP) is an increasingly common musculoskeletal disease and an important issue in the global healthcare system. Some studies have shown that the combination of manual therapy and exercise is effective in treating NSCNP but still with several limitations. Traditional Chinese manual therapy (tuina) is a Chinese manual therapy that consists of soft tissue manipulation and spinal manipulation. This study aims to design a randomized controlled trial to assess the effect of a tuina combined with specific therapeutic neck exercise modified protocol for NSCNP patients. Patients and Methods: This is a study protocol for a randomized, participant-, assessor- and analyst-blinded controlled trial. Eighty-eight eligible NSCNP patients will be randomly allocated into tuina combined with specific therapeutic neck exercise group (TSTE group) and tuina combined with sham therapeutic neck exercise group (TS group) in a ratio of 1:1. All participants will receive 8 treatment sessions applied in 4 weeks and then be followed up for another 12 weeks. Clinical data will be collected at baseline, during treatment phase (at the 2- and 4-week) and at the 8-, 12-, 16-week follow-ups. The primary outcome is the changes in neck pain intensity (visual analogue scale). The secondary outcomes include neck disability (Neck Disability Index), cervical range of motion (ROM), neck muscle endurance, cervical muscle cross-sectional area, cervical curvature and analgesic consumption. Adverse events will be collected and recorded throughout the study. Conclusion: We will discuss whether our tuina combined with specific therapeutic neck exercise modified protocol is more effective at improving pericervical muscle endurance, ROM, cervical muscle cross-sectional area and cervical curvature than tuina alone, thereby decreases neck pain and disability in individuals with NSCNP more effectively. Trial Registration: Chinese Clinical Trials Registry, ChiCTR2300067903. Registered on 31 January 2023.

Efficacy of five-step shoulder manipulation for rotator cuff-related shoulder pain: protocol for a multicenter randomized controlled trial.

BACKGROUND: Rotator cuff-related shoulder pain (RCRSP) is the most common cause of shoulder disorders. In China, manipulation has been used extensively for the treatment of patients with RCRSP. However, high-quality clinical evidence to support the therapeutic effect of manipulation is still limited. METHODS: A multicenter, participant-, outcome assessor-, and data analyst-blinded, randomized, placebo-controlled trial will be conducted. A total of 280 participants with RCRSP will be recruited from three hospitals and randomly assigned to a five-step shoulder manipulation (FSM) group or a sham manipulation (SM) group. Each group will receive four weekly treatment sessions, with all participants performing exercises at home for 12 weeks. Assessments, namely the Constant-Murley score, visual analog scale, range of motion, and 36-Item Short Form Survey, will be made at baseline, 4, 12, 18, and 24 weeks. Adverse events during the study will also be recorded. DISCUSSION: This is a pragmatic clinical trial to evaluate the efficacy and safety of FSM in patients with RCRSP. The findings of this study will provide worthy clinical evidence for manual therapy for RCRSP. TRIAL REGISTRATION: China Registered Clinical Trial Registration Center ChiCTR2000037577. Registered on 29 August 2020.

Clinical research for whether the Traditional Chinese medicine could promote the resorption of lumbar disc herniation: a randomized controlled trial.

Lumbar disc herniation (LDH) is a common, disabling musculoskeletal disorder. Magnetic resonance imaging has clarified the natural history of lumbar disc lesions and has documented that disc lesions can become smaller and can even be completely resorbed. Previous studies have confirmed that some traditional Chinese medicine (TCM) therapies can promote resorption of the protrusion. However, high-quality research evidence is needed to support the effectiveness of the protocol. OBJECTIVE: This clinical trial aims to establish whether TCM can promote the resorption of LDH and to assess the efficacy of such therapy for LDH, thereby evaluating its clinical effect. METHODS: The present study design is for a single-center, 2-arm, open-label randomized controlled trial. A total of 150 eligible LDH patients will be randomly assigned to either a TCM treatment group or a control group in a 1:1 ratio. Patients in the TCM group will be administered a TCM decoction for 4 weeks. Patients in the conventional drug control group will be instructed to take a specific daily dose of celecoxib. The primary outcome measure is the change from baseline in the volume of the protrusion, as assessed using MR images. Secondary outcome measures include visual analog scale pain scores and Japanese Orthopaedic Association scores assessed at 3 and 6 months. DISCUSSION: The design and methodological rigor of this trial will allow evaluation of the basic clinical efficacy and safety data for TCM in the treatment of patients with LDH. The trial will also assess whether TCM can promote the resorption of LDH. This research will therefore help provide a solid foundation for the clinical treatment of LDH and for future research in TCM therapy. TRIAL REGISTRATION: ChiCTR1900022377.

The efficacy and safety of 'antianxiety granule' for anxiety disorder: a multicentre, randomized, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: Anxiety disorders are the most prevalent class of lifetime disorders in China, and generalized anxiety disorder (GAD) is one of the most common but frequently overlooked anxiety disorders. Conventional pharmacological treatments for GAD have varying degrees of side effects, dependency, and/or withdrawal syndromes. Traditional Chinese medicine (TCM) is considered a valuable therapeutic option for anxiety disorders and a potentially effective technique to reduce the side effects associated with antipsychotic drugs. This trial aimed to evaluate the clinical efficacy and safety of Antianxiety Granule, a granular Chinese medicine compound, for treatment of GAD. METHODS/DESIGN: The current work is a multicentre, randomized, double-blind, placebo-controlled, parallel-group clinical trial with a 6-week treatment schedule. The study consists of three periods: a 1-7-day screening period, a 6-week primary treatment period, and a 1-week follow-up period. Follow-up assessments will be conducted 1 week after the last visit with a face-to-face interview or by telephone. The clinical efficacy of Antianxiety Granule for the treatment of GAD will be evaluated by examining the change in the Hamilton anxiety scale (HAMA) score, state-trait anxiety inventory (STAI) score, and TCM symptom scale in patients with GAD who receive daily TCM treatment. Moreover, an intention-to-treat (ITT) analysis will also be used in this randomized controlled trial (RCT). DISCUSSION: Our study is a multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the safety and efficacy of Antianxiety Granule for the treatment of GAD. The results of this trial will provide valuable clinical evidence for the treatment of GAD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016039. Registered on 8 May 2018.

Osteoprotective effects of osthole in a mouse model of 5/6 nephrectomy through inhibiting osteoclast formation.

The present study aimed to investigate the effects of osthole on osteoclast formation and bone loss in a mouse model of 5/6 nephrectomy. The mice in control and osthole groups were treated 1 month following 5/6 nephrectomy with either a placebo or osthole, respectively. At 2 months post­nephrectomy, the L4 vertebrae were harvested. The bone mineral density (BMD) of cancellous bone was measured using micro­CT and tartrate­resistant acid phosphatase (TRAP) staining was performed to evaluate osteoclast formation. Immunohistochemistry staining and reverse transcription­quantitative polymerase chain reaction were performed to detect the expression of nuclear factor of activated T­cells, cytoplasmic­1 (NFATc­1), c­Fos, cathepsin K, Trap, matrix metalloproteinase 9 (Mmp9), osteoprotegerin (Opg) and receptor activator for nuclear factor­κB ligand (Rankl). Bone marrow cells were cultured with osthole, and osteoclast formation was shown by TRAP staining. Primary calvaria osteoblasts were cultured with osthole, and expression levels of Opg and Rankl were detected. Compared with the sham group, the BMD of mice in model group was significantly reduced. The numbers of osteoclasts and the expression levels of NFATc­1, c­Fos, cathepsin K and Mmp9 were significantly increased. Compared with the control group, the mice in the osthole group exhibited increased BMD of the L4 vertebrae, a reduction in osteoclast numbers and decreased expression levels of NFATc­1, c­Fos, cathepsin K and Mmp9. In vitro experiments also showed that osteoclast formation was decreased following treatment with osthole. Osteoprotegerin (Opg)/receptor activator for nuclear factor­κB ligand (Rankl) was upregulated by osthole treatment in the L4 vertebrae and in primary cultures of calvarial osteoblasts. Osthole inhibited osteoclast formation and partially reversed the bone loss induced by 5/6 nephrectomy in mice through the upregulation of OPG/RANKL.

Analgesic mechanism of electroacupuncture in a rat L5 spinal nerve ligation model.

The aim of this study was to investigate the analgesic mechanism of electroacupuncture (EA) in the treatment of neuropathological pain. A total of 60 Sprague-Dawley rats were randomly divided into three groups, namely the spinal nerve ligation (SNL), electroacupuncture (SNL + EA) and normal control groups, with 20 rats in each group. The up-down method was used to determine the bipedal 50% mechanical paw withdrawal threshold (PWT). The ultrastructure of the injured-side L5 nerve root (n=6) was observed by electron microscopy. The mRNA levels of brain-derived neurotrophic factor (BDNF) and purinergic receptor P2X, ligand-gated ion channel 4 (P2X4) in the spinal cord (n=14) were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The postoperative PWT of the injured-side hindpaw in the SNL group at each time point was lower than that in the control group (P<0.01); there were differences of statistical significance between the PWT values of the SNL + EA and SNL groups on postoperative days 14 and 21 (P<0.05). Postoperatively, the PWT of the hindpaw on the uninjured-side was significantly lower in the SNL group when compared with that of the control group on days 10, 14 and 21 (P<0.05). Following the EA treatment, axonal demyelination was reduced and vascular proliferation was observed within the visual field. In addition, following the EA treatment, BDNF expression levels in the spinal dorsal horn increased (P<0.05), while the expression of P2X4 was not different from that in the SNL group. EA exerted an analgesic effect on the SNL model in a time-dependent manner, and improved the blood supply to the nerve root. Following the EA treatment, the expression of P2X4 did not change significantly compared with that in the SNL group, whereas the spinal secretion of BDNF increased. However, the exact mechanism requires further study.