Intrathecal injection of monocyte chemoattractant protein-2 neutralizing antibody reduces mechanical allodynia in a rat model of bone cancer pain

Objective To observe the effect of intrathecal administration of monocyte chemoattractant protein-2(CCL2) neutralizing antibody on pain behavior and explore its possible mechanisms. Methods Thirty-two female SD rats weighting 180-220 g were randomly divided into 4 groups(n=8): sham+IgG group (groupⅠ), sham+Anti-CCL2 intrathecal group (groupⅡ), model+IgG group (group Ⅲ), model+Anti-CCL2 group(group Ⅳ). Rats in group Ⅰ and group Ⅱ were injected with 10 μl Hank's solution into the left proximal tibial medullary cavity, rats in group Ⅲ and group Ⅳ were injected with 10 μl Walker 256 breast cancer cells(1×107/ml) into the same area. Von-Frey thresholds and thermal radiation reflection threshold were measured before modeling and at 1st, 3rd, 6th, 7th, 8th, and 9th day after surgery. The altered expression of phosphorylate extracellular signal-regulated kinases 1/2(p-ERK1/2) in spinal dorsal horn at different time point was detected by Western blot. Results Compared with rats in groupⅠ, von-Frey thresholds and thermal radiation reflection threshold significantly decreased in rats of group Ⅲ at the 6th day post-inoculation(P 0.05). Conclusions Intrathecal injection of CCL2 neutralizing antibody can partially release the mechanical and thermal allodynia induced by bone cancer pain, which may be related to blockade of p-ERK1/2 in the spinal dorsal horn. These results indicated that spinal CCL2 may be involved in the development of rats bone cancer pain via activation of p-ERK1/2 in the spinal dorsal horn. Key words: Bone cancer pain; Spinal cord; Monocyte chemoattractant protein-2; Phosphorylate extracellular signal-regulated kinases 1/2