Objective: To investigate the manifestation of ethology and the immunohistochemistry results of the 2B Subunits of N-methyl-D-aspartate receptors (NR2B) in the spinal cord dorsal horn and dorsal root ganglia (DRG) in mice with bone cancer pain and their correlation, and to discuss the role of NR2B in the generation and maintenance of bone cancer pain.
Methods: Forty-five male C57BL/6 mice were randomly divided into 3 groups: a model group (n=15), 2×10(6) cells in 10 μL D-Hank's were injected into the left femur of mice;a sham group(n=15), only 10 μL D-Hank's injected into the left femur of mice;and a normal control group(n=15), no treatment. Spontaneous lifting duration and mechanical withdrawal threshold of the hind paw of mice were measured on alternative days throughout the experiment. Bones from 5 mice in each group were stained with HE on Day 7, 15, and 23 after the inoculation and segments of lumbar spinal cord and L(4) DRG were taken to detect NR2B by immunohistochemistry.
Results: Bone cancer pain models were successfully established and confirmed by ethology and histology. The immunohistochemical positive indexes of NR2B were significantly higher in the model group than in the sham group and the control group. In the model group there were obvious differences either between Day 7 and Day 15, or between Day 7 and Day 23 (P<0.05). On Day 23, the immunohistochemical positive indexes of NR2B in the ipsilateral spinal cord dorsal horn of all groups, and L(4) DRG were positively correlated with the spontaneous lifting duration of ipsilateral hindpaw (r=0.976, P<0.001; r=0.882, P<0.001, respectively), negatively correlated with the mechanical withdrawal threshold of ipsilateral hindpaw (r=-0.879, P<0.001; r=-0.760, P=0.001, respectively).
Conclusion: The immunohistochemical positive indexes of NR2B are increased and significantly correlated with the manifestation of ethology. NR2B in the spinal cord and L(4) DRG may participate and mediate in forming and developing hyperalgesia in bone cancer pain.