Herbal
analgesic Xiaozheng Zhitong Paste (XZP) and related modifications are often used in
traditional Chinese medicine to manage
cancer pain. However, its underlying mechanism remains unknown. To investigate the effects and mechanism of XZP on
bone cancer pain in a rat model of
breast cancer-induced bone
pain, a
bone cancer pain model was established by inoculating Walker 256 cells into Wistar rats.
Bone cancer-bearing rats were topically treated with different doses of XZP or injected with 5 mg/kg of
osteoprotegerin (OPG) as positive control. Bone destruction, bone mineral content (BMC) and bone mineral density (BMD) were analyzed by radiology. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were examined to determine
pain levels.
Trypsin, TNF-α and IL-1β serum levels were determined using
enzyme-linked
immunosorbent assay (ELISA). Central sensitization markers such as c-Fos, GFAP, IBA1 and CGRP, as well as
proteinase-activated receptor 2 (PAR2) signaling pathway mediators such as PAR2, PKC-γ, PKA and TRPV1, were determined by quantitative RT-PCR and western blotting assay. XZP treatment significantly mitigated
bone cancer-related nociceptive behavior, bone damage, BMC and BMD; and decreased radiological scores in rats. XZP treatment significantly inhibited IBA1, GFAP, c-Fos and CGRP expressions in the spinal cord; and significantly mitigated
trypsin, TNF-α and IL-1β serum levels. Furthermore, PAR2, PKC-γ, PKA and TRPV1 relative
mRNA levels and
protein expression in bone lesions were significantly reduced in rats treated with XZP. XZP significantly alleviates
breast cancer-induced bone
pain by inhibiting the PAR2 signaling pathway.