Astilbin exerts anti-hypersensitivity by regulating metabolic demand and neuronal activity in rodent model of neuropathic pain

Objective Astilbe chinensis, is a traditional Chinese medicine commonly employed for pain management. However, its primary active ingredient remains a subject of debate.Methods Spinal nerve ligation (SNL) and formalin-induced pain models were employed. Network pharmacology and bioinformatics were utilized to identify targets. Verification was performed through spinal cord double immunofluorescence staining, quantitative PCR and whole-cell recording techniques.Results In experiments conducted on neuropathic rats, both systemic and intrathecal administration of astilbin, an essential constituent, exhibited a noteworthy and dose-dependently decrease in chronic and acute pain behaviours. The ED50 value, which represents the dose at which 50% effectiveness is achieved, was measure at 7.59 μg, while the Emax value, indicating the maximum attainable effect, was found to be 60% of the maximal possible effect (% MPE). Forty-two shared targets were identified, enriching the metabolic and synaptic pathways in the network pharmacology analysis, as confirmed by transcriptomic analysis. Weighted gene co-expression network analysis (WGCNA) revealed a strong correlation between the anti-nociceptive effects of astilbin and neuronal metabolic processes. Spinal functional ultrasound (FUS) analysis indicated increased spinal blood flow intensity and changes in metabolism-related enzyme activity, including stearoyl-CoA desaturase (Scd), 17beta-hydroxysteroid dehydrogenase (Hsd17b7) and sterol 14alpha-demethylase (Cyp51) in neuropathic rats, pretreatment with astilbin decreased formalin-induced blood flow in acute pain. Bath application of astilbin dose-dependently inhibited neuronal activity by reducing the frequency and amplitude of miniature excitatory postsynaptic currents (mEPSCs) without affecting miniature inhibitory postsynaptic currents (mIPSCs).Conclusions In summary, this study provides evidence that astilbin alleviates pain by modulating neuronal metabolic processes and synaptic homeostasis.