Abstract: Objective · To investigate the effects of CC chemokine ligand 2 (CCL2) on pain behavior in a rat model of bone cancer pain (BCP) and the underlying peripheral mechanisms. Methods · BCP models were developedinoculation of Walker256 mammary gland carcinoma cells into the tibia medullary cavities of right hind limbs SD rats. The same volume of saline was injected in sham operation (sham) group. The mechanical pain threshold was measured to judge the success of BCP model. Expression of CCL2 in L4 and L5 dorsal root ganglion (DRG) was detectedimmunofluorescence staining. CCL2 (500 ng, 25 μL) was injected into plantar of the operated side to observe its effects on leg-raising and foot-licking behaviors of hind paws in BCP and sham rats. Whole-cell patch-clamp recording was used to investigate the effects of CCL2 on membrane potential of acutely dissociated DRG neurons the two groups. Results · Fourteen days after operation, the mechanical pain threshold in the right hind paws of BCP rats was significantly lower than that in sham rats. Compared with the Sham rats, the of CCL2 in L4 and L5 DRG of BCP rats was significantly higher. Plantar injection of CCL2 increased paw lift time in BCP rats. The rate and amplitude of depolarization inducedCCL2 in BCP DRG neurons were significantly higher than those in sham neurons. Conclusion · CCL2 facilitates pain behavior in BCP rats, and its peripheral mechanism maybe involves CCL2-induced neuron depolarization to enhance excitability of DRG neurons. These results indicate that CCL2 plays an important role in development of BCP.

Key words: CC chemokine ligand 2, bone cancer pain, dorsal root ganglion, membrane potential, depolarization