The Reactions of Glial Cells and Endoneurial Macrophages in the Dorsal Root Ganglion and Their Contribution to Pain-Related Behavior After Application of Nucleus Pulposus Onto the Nerve Root in Rats

Abstract

Controlled, interventional, animal study. To observe the reaction of glial cells and endoneurial macrophages in the dorsal root ganglion (DRG) after application of nucleus pulposus (NP) and investigate whether activated DRG glial cells play a role in the pathogenesis of neuropathic pain. Peripheral nerve injury activated DRG and spinal cord glial cells and several cytokines and neurotrophins released from these activated glial cells might induce pain hypersensitivity. Adult male Sprague-Dawley rats were used. NP harvested from the tail was applied to the left L5 DRG. Behavioral testing was performed to investigate the mechanical withdrawal threshold. The numbers of activated satellite glial cells and endoneurial macrophages were counted, and the expressions of tumor necrosis factor-alpha (TNF-alpha) and glial cell-line derived neurotrophic factor (GDNF) were examined by double-labeled immunohistochemistry and immunoblotting. The mechanical withdrawal threshold was significantly decreased for 28 days and then gradually recovered (P < 0.05). Long-term activation of endoneurial macrophages and satellite glial cells in the DRG was observed, and the reactions of these cells correlated well with pain-related behavior. TNF-alpha was expressed in both endoneurial macrophages and activated satellite glial cells, and TNF-alpha expression was significantly increased in the early stage (P < 0.05). Activated satellite glial cells also expressed GDNF, and its expression was significantly increased and persisted for 28 days (P < 0.05). Activation of DRG glial cells and endoneurial macrophages plays an important role in the pathogenesis of the neuropathic pain state. TNF-alpha actively released from activated glial cells and endoneurial macrophages in the DRG might initiate and maintain the neuropathic pain together with TNF-alpha derived from the applied NP. In the recovery phase, persistent expression of GDNF from activated satellite glial cells might play an important role to restore the function of damaged neurons and recover from neuropathic pain.