Duhuo Jisheng Mixture attenuates neuropathic pain by inhibiting S1PR1/P2Y1R pathway after Chronic Constriction Injury in mice

• Published in: Phytomedicine (Stuttgart) 2025-01, Vol.138, p.156413, Article 156413
• Main Authors: Li, Ruili, Zhang, Wei, Bai, Xiaodan, Wang, Fan, Yao, Minna, Zhao, Chao, Wang, Jingwen
• Format: Article
• Language: English
• ISSN: 0944-7113; 1618-095X; 1618-095X
• DOI: 10.1016/j.phymed.2025.156413

The pathogenesis of neuropathic pain is complex and lacks effective clinical treatment strategies. Medical plants and herbal extracts from traditional Chinese medicine with multi-target comprehensive effects have attracted great attention from scientists.BACKGROUNDThe pathogenesis of neuropathic pain is complex and lacks effective clinical treatment strategies. Medical plants and herbal extracts from traditional Chinese medicine with multi-target comprehensive effects have attracted great attention from scientists.To investigate the pharmacological active components and mechanism underlying the anti-neuralgia effect of classic analgesic formulas Duhuo Jisheng Mixture (DJM).PURPOSETo investigate the pharmacological active components and mechanism underlying the anti-neuralgia effect of classic analgesic formulas Duhuo Jisheng Mixture (DJM).Chronic Constriction Injury (CCI) surgery was used to assess the efficiency of DJM in treating neuropathic pain. Forty-two C57BL/6 mice were evenly divided into seven groups: sham-operated, sham treatment with DJM (20 ml/kg), CCI treatment with DJM (0, 10, 20, or 40 ml/kg) and CCI treatment with Morphine (3 mg/kg). DJM irrigation stomach was implemented from post-operative day (POD) 0 to POD 21. Paw withdrawal threshold and Thermal latency were conducted on POD 0, 1, 3, 5, 7, 14 and 21. On POD 14, eEPSP in spinal dorsal horn neurons was recorded by patch-clamp. mRNA transcription in spinal cord was also monitored to screen molecular targets and signaling pathways on POD 14. To further validate the influence of DJM on the S1PR1 signaling pathway, 1 mg/kg W146 was infused into mice intrathecally and delivered to the cerebral spinal fluid through one 30 G needle with a whole 20 μl intervertebral between the L5 and L6. Furthermore, the active ingredients of DJM were identified through LC/MS equipment and predicted through Molecular Docking.STUDY DESIGN AND METHODSChronic Constriction Injury (CCI) surgery was used to assess the efficiency of DJM in treating neuropathic pain. Forty-two C57BL/6 mice were evenly divided into seven groups: sham-operated, sham treatment with DJM (20 ml/kg), CCI treatment with DJM (0, 10, 20, or 40 ml/kg) and CCI treatment with Morphine (3 mg/kg). DJM irrigation stomach was implemented from post-operative day (POD) 0 to POD 21. Paw withdrawal threshold and Thermal latency were conducted on POD 0, 1, 3, 5, 7, 14 and 21. On POD 14, eEPSP in spinal dorsal horn neurons was recorded by patch-clamp. mRNA