Study on the Analgesic and Compatibility Mechanism of Yuan-Hu Zhi Tong Prescription for Alleviating CCI-induced Neuropathic Pain

Neuropathic pain (NP) is a complex chronic pain due to the nervous system damage or diseases.Yuan-Hu Zhi Tong Prescription (YZP) is a well-known Traditional Chinese Medicine (TCM) formula for pain relief, which is composed of Corydalis Rhizoma (Yuanhu, YH) and Angelicae Dahuricae Radix (Baizhi, BZ). However, understanding of the analgesic and compatibility mechanisms of YZP remains limited. The present study found that YZP was more effective in relieving mechanical allodynia and thermal hypersensitivity than YH and BZ administered alone. To understand the potential analgesic and compatibility mechanisms of YZP on neuropathic pain (NP), RNA-seq and bioinformatics analyses were performed. The results revealed that YZP exerts analgesic effects mainly by relieving inflammation in the spinal cord through various mechanisms, such as suppressing leukocyte activation and cytokine-mediated signaling pathways. Moreover, YZP can relieve NP by modulating the neuropeptide signaling pathway and promoting damaged tissue regeneration. In terms of compatibility, YH and BZ demonstrated synergistic effects on the inflammatory response and neuropeptide signaling pathway. Furthermore, BZ was found to regulate calcium ion transport and promote skeletal muscle tissue regeneration, thereby alleviating concomitant symptoms of NP. Hub genes such as Ucn, Ptgs2, Gal, and others may play a pivotal role in YZP analgesia and the synergistic effects of YH-BZ compatibility. Overall design: The CCI rats were randomly assigned to four groups: the CCI group, the CCI+YZP group, the CCI+YH group, and the CCI+BZ group, with 7 rats in each group. YZP (10.8 g crude drug/kg), YH (7.2 g crude drug/kg,) and BZ (3.6 g crude drug/kg) were administered respectively and continuously for 5 days from the postoperative day (POD) 6 to 10. The ipsilateral L4-L6 SC of rats were collected on POD 10, immersed in TRIzol (Invitrogen, CA, USA), and immediately frozen in liquid nitrogen for the RNA-seq (n=3 per group).