Role of TRPA1 in allodynia and hyperalgesia in rats with bone cancer

Objective To establish bone cancer pain model by injecting Walker 256 tumor cells into tibial medullary canal of rats,and investigate the role of TRPA1 in occurrence and development of bone cancer pain. Methods Twelve female SpragueDawley rats were randomly divided into sham operation group(10μl of 0.9 sodium chloride injection)and bone cancer pain model group(10μl of Walker 256 tumor cells),with 6 rats in each group.The paw mechanical withdraw threshold and the paw thermal withdraw latency in the two groups at 1 day before operation and at 3,5,7,9,11,13,14 days after operation were detected X-ray and pathological examination were performed at 14 days after operation.The expression of TRPA1 protein in the two groups was detected by western blot.Another 10 female Sprague-Dawley rats were randomly divided into bone cancer pain+TRPA1 antagonist(A967079)group(10 mg/kg 10 μl)and bone cancer pain+ saline group(10μl),with 5 rats in each group.The paw mechanical withdraw threshold and the thermal withdraw latency in each group were measured at 1 hour before administration and at 2,4,6 and 8 hours after administration. Results At 14 days after operation,X-ray imaging showed that tibial bone was destructed,and HE pathological sections showed atypia tumor cells,indicating that the bone cancer pain model was successfully induced.Compared with sham operation group,the weight,paw mechanical withdraw threshold,thermal withdraw latency-hot,thermal withdraw latencycold in rats of bone cancer pain group were significantly lower(all P<0.01),and the relative protein expression of TRPA1 in rats of bone cancer pain group was higher(P<0.01).After TRPA1 antagonist(A967079)was administrated at 7 days after operation,mechanical allodynia alleviated at 2 h and 4 h after treatment in rats with bone cancer pain; and the paw thermal withdraw latencyhot was also elevated(all P<0.01). Conclusion TRPA1 mediates mechanical hyperalgesia and temperature allodynia in bone cancer pain model.