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.

Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling.

Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show potential as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves as an osteoclast differentiation regulator without causing cytotoxicity. However, the in vivo functions of AC in various OP models need clarification. To address this, we administered intraperitoneal injections of AC to ovariectomy (OVX)-induced OP mice for 8 weeks and found that AC effectively reversed the OP phenotype of OVX mice, leading to a reduction in vertebral bone loss and restoration of high bone turnover markers. Specifically, AC significantly suppressed osteoclastogenesis in vivo and in vitro by decreasing the expression of osteoclast-specific genes such as NFATc1, c-Fos, Cathepsin K, and Mmp9. Importantly, AC can regulate osteoclast ferroptosis by suppressing Gpx4 and upregulating Acsl4, which is achieved through inhibition of the phosphorylation of I-κB and p65 in the NF-κB signaling pathway. These findings suggest that AC is a potential therapeutic option for managing OP by suppressing NF-κB signaling-mediated osteoclast ferroptosis and formation.