Effects of Intrathecal Administration LXM-10 on the Expression of FOS Protein and P2X3 Receptor in Neuropathic Pain Rat Models
PANG Hong-Jie;JIN Xu;WANG Bao-Guo.
2010, 5(03):
34-39.
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Objective To investigate the changes of Fos protein and P2X3 receptor's expression in rats withneuropathic pain in spinal cord dorsal horn and dorsal root ganglion (DRG) after intrathecalinjection of new analgesic drugs LXM-10.Methods One hundred and eight adult SD rats were randomly divided into three groups (n=36each): the sham operation group (S group), the control group (C group) and the LXM-10 group(L group). The control group and XM-10 group were made into the chronic constriction injury ofthe sciatic nerve(CCI-SN) model. The operation group, control group and XM-10 group had beendivided into three sub-groups (n=12 each) according to the injection time points. On the day 1, 5,12 after CCI-SN, control group and XM-10 group were subarachnoid injected with correspondingdrugs: normal saline 10μl for C3 group, C7 group, C14 group, or LXM-10 6.0μg/kg for L3group, L7 group and L14 groupcontinuous 3 days, respectively. The sham operation group wereintrathecally injected with normal saline 10μl for S3 group, S7 group, S14 group. After intrathecallyadministrating relevant drugs (normal saline or LXM-10) for 3 days, the rats were sacrificed in two hours after the last administration, and their spinal cord and L4-6 DRG were collected immediately.The expression of Fos protein and P2X3 receptor were measured with immunohistochemistry tests.Results The expression of Fos protein in the control group at each time point increased with time,and it was mainly expressed in the spinal cord dorsal horn. Compared with the control group ateach time point,the Fos-like immunoreactivity(F-LI) cells in LXM-10 group decreased significantly.(The L3 group compared with the C3 group, P =0.003; the L7 group compared with the C7 group,P =0.023; the L14 group compared with the C14 group, P =0.005.) The changes of Fos proteinexpression in DRG was similar to relevant spinal cord. (The L3 group compared with the C3 group,P =0.002; the L7 group compared with the C7 group, P =0.003; the L14 group compared with theC14 group, P =0.002.) The expression of P2X3 was up-regulated in all CCI-SN groups. The P2X3positive expression could be easily observed in L4-6 DRG. Compared with the control group, theexpression of P2X3 positive cells in the LXM-10 group at each time point decreased in the spinalcord dorsal horn. (L3 group compared with C3 group, P =0.043; L7 group compared with C7 group,P =0.008; L14 group compared with C14 group, P =0.005.) After intrathecal administration in DRG,the expression of P2X3-positive cells significantly reduced at each time point. (L3 group comparedwith C3 group, P =0.034; L7 group compared with C7 group, P =0.001; L14 group compared withC14 group, P =0.003.)Conclusion For the neuropathic pain rats, after CCI of rats’ sciatic nerve, both Fos proteinand P2X3 receptor’s expression were up-regulated in the dorsal horn of spinal cord and DRG.Intrathecally administrated LXM-10 could significantly inhibit the expression of Fos and P2X3proteins. Intrathecal administration LXM-10 can significantly reduce the expression of the two.
