The
Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with
pain,
spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar
disc herniation, and the efficacy and mechanism of
Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that
Baimai Ointment significantly improved the pain thresholds(mechanical
pain, thermal
pain, and cold
pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects.
Baimai Ointment inhibited the second-phase nociceptive response of mice in the
formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory
cytokines in the spinal cord. Network analysis showed that
Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and
neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the
pain-relieving effect of
Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive
ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory
element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of
Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.