Biomolecular network-based synergistic drug combination discovery:a combination of paeoniflorin and liquiritin alleviates neuropathic pain by inhibiting neuroinflammation via suppressing the chemokine signaling pathway

Dear Editor,Neuropathic pain(NP)resulting from injuries or diseases affecting the somatosensory nervous system is highly prevalent in various pathological conditions.1 Since NP is debilitating and impacts health and the quality of life,there is an urgent need for effective non-addictive new therapies.Traditional Chinese medicine(TCM)has been increasingly used for its benefits in relieving pain in clinics.Wu-Tou Decoction(WTD),which was first described by the famous TCM classic“Jin Gui Yao Lue”,is one of the most effective TCM herbal prescriptions for pain management.A growing body of clinical evidence shows that WTD markedly alleviates different types of NP,such as trigeminal neuralgia,inflammatory pain,and cancer-induced pain,with a total effectiveness of~80%.2 Our previous data demonstrated the analgesic effects of WTD via suppression of glial cell activation and neuroinflammation and further revealed that WTD attenuated NP partially by inhibiting spinal astrocytic IL-1R1/TRAF6/JNK signaling and regulating the glutamatergic system in CA3 in spinal nerve ligation(SNL)-induced NP in vivo.3,4 However,the bioactive compounds(BACs)of WTD that have an effect on NP and the underlying mechanisms remain unclear.