Objective: To explore the analgesic initiation mechanism of the three-manipulation and three-acupoint of tuina on rats with minor CCI model. Methods: 56 SD rats were randomly divided into 8 groups: normal group, sham group, model 1 group, model 2 group, tuina 1 group, tuina 2 group, tuina 1 + TRPA1 antagonist group, and tuina 2 + TRPV1 antagonist group. The model group, tuina group, and tuina + antagonist group were established with minor CCI models. The tuina group and tuina + antagonist group received the three-method three-point intervention (point method, dial method, kneading method, Yinmen point, Chengshan point, Yanglingquan point) 7 days after modeling. The model group and sham group were subjected to grasping restraint, and the normal group was not intervened. After the intervention, each group was tested for changes in thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) to detect different types of pain. The nitrate reductase method was used to observe the NO content in the DRG of each group on the modeling side, and ELISA, Western blot, qPCR, and other methods were used to observe the changes in the protein and gene expression of the TRPV1/TRPA1-NO-cGMP-PKG signaling pathway in the DRG of each group on the modeling side. Results: Compared with the model group, behavioral testing showed that the MWT and TWL were prolonged to varying degrees in the tuina 1 group and tuina 2 group. The expression of TRPV1, TRPA1, NO, sGCβ, cGMP, and PKG1 in the DRG of the tuina 1 group, tuina 2 group, tuina 1 + TRPA1 antagonist group, and tuina 2 + TRPV1 antagonist group were significantly decreased. Conclusion: Tuina intervention can effectively improve the symptoms of thermal and mechanical hyperalgesia caused by peripheral nerve injury after one intervention. Tuina can exert immediate analgesic effects through the TRPV1/ TRPA1-NO-cGMP-PKG signaling pathway.