Neuropathic pain (NPP) is a debilitating clinical condition that presently has few effective treatments. NPP is caused by uncontrolled central oxidative stress and inflammation. Preliminary studies indicate that dexmedetomidine (DEX), an agonist of the alpha-2 adrenergic receptor, is beneficial for treating NPP. In this paper, the effects of administering DEX around injured nerves in a chronic constriction injury- (CCI-) induced neuropathic pain mouse model are investigated. According to the results, the perineural DEX significantly reversed the decline in the mechanical threshold and thermal latency in CCI mice ( p < 0.001 ). In the peripherally affected ischiadic nerve, the perineuronal DEX upregulated the expressions of pAMPK, OPA1, and SNPH but not Drp1 or KIF5B. The aforementioned effects of administering DEX can be partially reversed by compound C, a selective and reversible inhibitor of AMP-activated protein kinase (AMPK). Furthermore, it was found that perineural DEX significantly inhibited the CCI-induced upregulation of the immediate early gene c-Fos, overexpression of the inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), attenuation of the NADH dehydrogenase complexes I, II, III, and IV, and the repression of ATP, SOD, and GSH in the dorsal horn of the spinal cord (DHSC) ( p < 0.01 ). These findings indicate that perineuronal DEX protected the injured ischiadic nerves and attenuated neuropathic pain via AMPK activation to improve energy supply in the peripheral injured nerves, alleviate the inflammatory factor release, and inhibit oxidative stress in the DHSC.

Introduction Adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) can influence energy metabolism. Energy metabolism imbalance is closely associated with the occurrence of neuropathic pain (NeP). Rs10789038 and rs2796498 are genetic polymorphisms of PRKAA2 , the gene encoding AMPK, which is closely related to energy metabolism imbalance. This study aimed to explore the relationship between PRKAA2 and postherpetic neuralgia (PHN) in the southwestern Chinese Han population. Methods This study enrolled 132 PHN patients and 118 healthy subjects. The rs10789038 and rs2796498 PRKAA2 genotypes were identified in all participants. The association between these single nucleotide polymorphisms and PHN susceptibility was evaluated in the dominant and recessive models. Haplotype analysis of patients with PHN and healthy controls was performed. Results The PHN patients were older than the healthy subjects ( P < 0.05); however, the other clinical characteristics between two groups were not significantly different (all P >0.05). Genotypes and allele frequencies differed significantly between PHN patients and healthy subjects in the rs10789038 polymorphism ( P < 0.05), but not in rs2796498 ( P > 0.05). In addition, the GG haplotype of rs10789038-rs2796498 correlated negatively with PHN occurrence in haplotype analysis ( P < 0.05). Conclusion PHN occurrence may be related to the PRKAA2 rs10789038 A>G genetic polymorphism in the southwestern Chinese Han population.

BackgroundPost-stroke depression (PSD) is a common psychiatric complication of mental disorders after stroke. Acupuncture for PSD is effective and has few adverse effects. As a classical complementary and alternative therapy, acupuncture is often used in combination with antidepressants for PSD. However, there is a wide variety of acupuncture therapies, and the efficacy of different acupuncture varies. In this study, a network meta-analysis (NMA) was used to assess the clinical efficacy of different acupuncture combined with antidepressants for the treatment of PSD.MethodsA comprehensive search of PubMed, The Cochrane Library, EMbase, Web of Science, CNKI, CBM, VIP, and Wan-Fang databases for published randomized controlled trials of acupuncture combined with antidepressants for the treatment of PSD was conducted. The time frame for the literature search was from the date of database creation to April 30, 2022. The Cochrane risk of bias tool for randomized trials (RoB 2.0) was used to evaluate the bias risk of the included studies. Data analysis was performed by STATA 14.0 software.ResultsA total of 38 literatures with 2,898 patients involving nine acupuncture therapies were included. NMA results were as follows: moxibustion plus antidepressants had the best efficacy in terms of improving total effective rate. Conventional acupuncture plus antidepressants was the most effective in improving HAMD scores. In terms of improving SDS scores, acupressure plus antidepressants was the most effective. In terms of improving NIHSS scores, moxibustion plus antidepressants showed the best results.ConclusionA comparison of the efficacy indicators of the nine different acupuncture therapies combined showed that moxibustion plus antidepressants, conventional acupuncture plus antidepressants and acupressure plus antidepressants were superior in the treatment of PSD. Based on the shortcomings of the existing studies, this conclusion needs to be validated by additional high-quality randomized controlled trials.