The Role And Mechanism Of Sympathetic Sprouting In A Rat Model Of Neuropathic Pain

ObjectiveTo investigate the regulatory mechanism of sympathetic nerve on neuropathic pain.We inject the sympathetic blocking agent guanethidine to the rats with chronic compression of the dorsal root ganglion(CCD),and observe the distribution of sympathetic sprouting in dorsal root ganglion(DRG).Investigating the effect of sympathetic sprouting on the pain behavior of rats contributes to explore the role of sympathetic sprouting in the mechanism of neuropathic pain.Methods1.Male SD rats were randomly divided into Sham group and CCD group.The von Frey filaments were used to quantify the 50% paw mechanical withdrawal threshold of the rats in each groups.Separated DRGs of each group at the28 thday after modeling,and fixed with paraformaldehyde.The distribution of sympathetic sprouting in DRG was observed with immunofluorescence staining method to analyse the relationship with rats pain behavior.2.Male SD rats were randomly divided into Sham group,CCD+NS group and CCD+Guanethidine(CCD+GU)group.The von Frey filaments were used to quantify the 50% mechanical withdrawal threshold of the rats in each groups before and after intraperitoneal injection of the sympathetic blocking agent guanethidine.Besides,separated DRGs of each group at the28 thday after modeling,and fixed with paraformaldehyde.Finally,the distribution of sympathetic sprouting in DRG were measured and compared in different groups in order to study the influence of sympathetic nerve on the neuropathic pain.Results1.We found that the 50% paw mechanical withdrawal threshold of the CCD group decreased remarkably after operation,and it was much lower than the Sham group(P<0.01).In addition,the distribution of sympathetic sprouting in DRG of rats increased significantly at the 28 th day after CCD operation which was much higher than the Sham group(P<0.01).2.Intraperitoneal injection of the sympathetic blocking agent guanethidine can obviously increase the 50% mechanical withdrawal threshold of the CCD group.Compared with CCD+NS group,the 50% Paw withdrawal threshold in CCD+GU group was obviously different(P<0.01).Immunofluorescence staining showed that guanethidine can decrease the distribution of sympathetic sprouting of CCD model significantly.Comparing with the CCD+NS group,there was statistical difference(P<0.01).Conclusion1.The distribution of sympathetic sprouting in DRG of CCD rats increased significantly,and persistent compression of DRG can also reduced the mechanical pain threshold.This showed that sympathetic sprouting in DRG may be involved in the generation and maintenance of neuropathic pain.2.Sympathetic blocking agent guanethidine obviously relieved the mechanical hyperalgesia induced by CCD operation,in the meantime reduced the distribution of sympathetic sprouting in DRG of CCD rats,which further explained the sympathetic nerve system may be associated with the generation and maintenance of neuropathic pain.