Many cases of acute pain can be resolved with few side effects. However, some cases of acute pain may persist beyond the time required for tissue injury recovery and transit to chronic pain, which is hard to treat. The mechanisms underlying pain transition are not entirely understood, and treatment strategies are lacking. In this study, the hyperalgesic priming model was established on rats to study pain transition by injection of carrageenan (Car) and prostaglandin E2 (PGE2). The expression levels of protein kinase C epsilon (PKCε) and transient receptor potential vanilloid 1 (TRPV1) in the L4–L6 dorsal root ganglion (DRG) were investigated. Electroacupuncture (EA) is a form of acupuncture in which a small electric current is passed between a pair of acupuncture needles. EA was administrated, and its effect on hyperalgesia and PKCε and TRPV1 expression was investigated. The PKCε–TRPV1 signaling pathway in DRG was implicated in the pain transition. EA increased the pain threshold of model animals and regulated the high expression of PKCε and TRPV1. Moreover, EA also regulated hyperalgesia and high TRPV1 expression induced by selective PKCε activation. We also found that EA partly increased chronic pain threshold, even though it was only administered between the Car and PGE2 injections. These findings suggested that EA could prevent the transition from acute to chronic pain by inhibiting the PKCε and TRPV1 expression in the peripheral nervous system.

Background and Objective Dan-Hong injection, which comprises extracts of Salvia miltiorrhiza and Carthamus tinctorius, promotes blood circulation and reduces blood stasis. Combination of S. miltiorrhiza and C. tinctorius is more effective in treating cerebral ischemia than S. miltiorrhiza alone. This study aimed to examine the pharmacokinetic characteristics of four active ingredients of S. miltiorrhiza and C. tinctorius, namely danshensu (DSS), hydroxysafflor yellow A (HSYA), and salvianolic acid A (SAA) and B (SAB) in normal and cerebral ischemia rats. Methods Normal and cerebral ischemia rats were injected via the tail vein with each active ingredient, and blood was collected through the jaw vein at different time points. The plasma concentration of the compatibility group was analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using Pharmacokinetic Kinetica 4.4 software. Results The pharmacokinetics of the four active ingredients in the normal and cerebral ischemia rats were consistent with a two-compartment model. The area under the concentration–time curve was higher in normal rats than in cerebral ischemia rats, with a highly significant difference for SAA (P < 0.01). Clearance rates were lower in normal rats than in cerebral ischemia rats, with DSS showing the most significant difference (P < 0.01). Furthermore, there were significant differences between normal and cerebral ischemia rats in the distribution phase-elimination half life for DSS, SAA, and HSYA, as well as in the apparent volume of distribution for the central compartment for DSS and HSYA (P < 0.01). The plasma concentrations of the four active ingredients were higher in normal rats than in cerebral ischemia rats. Conclusion Cerebral ischemia rats showed higher drug clearance rates and longer retention times than normal rats, which may be due to destruction of the blood–brain barrier during cerebral ischemia–reperfusion. The four active ingredients likely integrated and interacted with each other to affect target sites in the brain to protect against cerebral ischemic injury.

Pain is a complex physiological phenomenon driven by dynamic microglial(MG) regulation in the CNS. Aberrant microglial activation mediates neuroinflammation, neuronal hyperexcitability, and synaptic plasticity, exhibiting spatiotemporal and sex-specific heterogeneity. While early pharmacological interventions show time-limited efficacy, electroacupuncture (EA) emerges as a potent non-pharmacological strategy that disrupts microglia-neuron crosstalk via multiple pathways. Critically, EA’s efficacy depends on intervention timing, with early application preventing microglial active in neuropathic models. Recent advances reveal CD11c⁺ microglia as dual regulators of pain resolution and relapse—clearing myelin debris acutely but driving recurrence via MMP-9-mediated synaptic remodeling. This review synthesizes microglial heterogeneity, stage-specific interventions, and EA’s translational potential in rebalancing microglial phenotypes for precision pain management.

The pathogenesis of chronic pain is complex and poorly treated, seriously affecting the quality of life of patients. Electroacupuncture (EA) relieves pain by preventing the transition of acute pain into chronic pain, but its mechanism of action is still unclear. Here, we aimed to investigate whether EA can inhibit pain transition by increasing KCC2 expression via BDNF-TrkB. We used hyperalgesic priming (HP) model to investigate the potential central mechanisms of EA intervention on pain transition. HP model male rats showed significant and persistent mechanically abnormal pain. Brain derived neurotrophic factor (BDNF) expression and Tropomyosin receptor kinase B (TrkB) phosphorylation were upregulated in the affected spinal cord dorsal horn (SCDH) of HP model rats, accompanied by K⁺-Cl^-- Cotransporter-2 (KCC2) expression was down-regulated. EA significantly increased the mechanical pain threshold in HP model male rats and decreased BDNF and p-TrkB overexpression and upregulated KCC2 expression. Blockade of BDNF with BDNF neutralizing antibody attenuated mechanical abnormal pain in HP rats. Finally, administration of exogenous BDNF by pharmacological methods reversed the EA-induced resistance to abnormal pain. In all, these results suggest that BDNF-TrkB contributes to mechanical abnormal pain in HP model rats and that EA ameliorates mechanical abnormal pain through upregulation of KCC2 by BDNF-TrkB in SCDH. Our study further supports EA as an effective treatment to prevent the transition of acute pain into chronic pain.