Research on the analgesic effect and mechanism of gabapentin on rats model with tibia metastatic cancer pain / 中国生化药物杂志

ABSTRACT

Objective To study the analgesic effect and mechanism of gabapentin on tibia metastatic cancer pain rat model constructed by walker-256 breast cancer cells.Methods 30 Female wistar rats were randomly divided into sham group,model group and GBP group(100 mg/kg),each group had 10 rats.Sham operation were used as operation control and tibia metastatic cancer pain operation were done separately.Paw withdrawal mechanical threshold and observation of X-ray were used to evaluate rats’pain behavior.ISCUS biochemical method,radioimmunoassay,and streaming multi-factor detection technique were used to detect glutamate level of cerebrospinal fluid,substance P level in the spinal cord and expression of IL-12P70,IFN-γ,β-NGF in the tumor tissue.Results Compared with sham group,paw withdrawal mechanical threshold of tibia metastatic rat model in operaion group were decreased significantly,and X-ray showed bone destruction,the glutamate level of cerebrospinal fluid and substance P level in the spinal cord were increased significantly(P<0.01 or P<0.05).IL-12P70 and IFN-γlevels were significantly lower andβ-NGF level was higher than that in sham group (P<0.05).Compared with model group,paw withdrawal mechanical threshold of rats in gabapentin group began to rise in 30 min after administration,and peaked in 60~300 min(P<0.01).Gabapentin reduced the glutamate level of cerebrospinal fluid,substance P level in the spinal cord andβ-NGF level of tumor tissue concentrations significantly(P<0.01 or P<0.05),but increased IL-12P70 and IFN-γlevels of tumor tissue.Conclusion Gabapentin can relieve the bone cancer pain of rat model.Its analgesic mechanism may lie indecreasing the levels of central excitatory amino acids,pain-associated neuromodulator and the nerve growth factor,and enhancing the peripheral immune function.