Intrathecal MCP-1Neutralizing Antibody Injection Reduces Mechanical Allodynia In A Rat Model Of Bone Cancer Pain

Objective To investigate expression change of MCP-1in the spinal cord of bonecancer pain rats.Methods34female SD rats weighing180～200g were randomly divided into2groups: Sham group (J group, n=17), Model group (M group, n=17). Rats in J group and Mgroup were respectively injected with10μl Hank’s solution or Walker256breast cancercells (1×10~/ml) into the left proximal tibial medullary cavity. At the day before and6,12,18d after inoculation, the change of Von-Frey threshold for mechanical allodynia wasobserved. Rats of the two groups were sacrificed pre-inoculation and on the6th,12th,18thpost-inoculaition, the L4~6spinal cord was removed. The expression of the spinal MCP-1was detected by real-time PCR.Results From the6th to18th day post-inoculation, Von-Frey threshold of rats in Mgroup significantly decreased (P<0.01) and rats appeared visible mechanical allodynia. Atthe same time, the expression profile of spinal MCP-1increased accordingly, on the6th,P<0.05vs. sham, on the12th and18th, P<0.01vs. sham.Conclusion MCP-1in the spinal cord may be involved in the generation andmaintenance of rat’s bone cancer pain.Part two: The effect of intrathecal MCP-1neutralizing antibody injectionon mechanical allodynia in a rat model of bone cancer painObjective To observe the effection of intrathecal MCP-1neutralizing antibody injection on pain behavior and the level of microglia expression in spinal cord in a ratmodel of bone cancer pain, then explore its possible mechanisms.Methods40female SD rats weighing180～220g were randomly divided into5groups(n=8): group Ⅰ,control group; group Ⅱ, model group; group Ⅲ, control+Anti-MCP-1intrathecal (i. t.); group Ⅳ, model+IgG i. t.; group Ⅴ, model+Anti-MCP-1i. t…Rats in group Ⅰ and group Ⅲ were injected with10μl Hank’s solution into the leftproximal tibial medullary cavity; Rats in group Ⅱ, group Ⅳ and group Ⅴ were injectedwith10μl Walker256breast cancer cells (1×107/ml) into the left proximal tibial medullarycavity.Results Compared with rats in group Ⅰ or group Ⅲ,Von-Frey thresholdssignificantly decreased in rats of group Ⅱ, Ⅳ and Ⅴ at the6th day post-inoculation;Atthe same time, Von-Frey thresholds profoundly elevated in rats of group Ⅴcompared withthose in group Ⅱ and Ⅳ. Compared with rats in group Ⅰ, the expression of OX-42(microglia marker) in spinal dorsal horn from group Ⅱ and Ⅳ apparently increased(P<0.01).Spinal dorsal horn OX-42protein levels of rats in group Ⅴ were lower relativeto group Ⅱ and group Ⅳ. There was no remarkable difference between group Ⅲ andgroupⅠ in the expression of spinal dorsal horn OX-42.Conclusion Intrathecal MCP-1neutralizing antibody injection can partialy releasemechanical allodynia induced by bone cancer pain, and this effect may be related toblockade of microglia activation in the spinal dorsal horn. These results indicate that spinalMCP-1may be involved in the development of rats bone cancer pain via activation ofmicroglia in the spinal dorsal horn.