Proinflammatory cytokines may sensitize primary sensory neurons and facilitate development of neuropathic pain processes after peripheral nerve injury. The goal of this study was to determine whether responses of dorsal root ganglion (DRG) neurons to exogenous tumor necrosis factor α (TNF-α) are altered in a chronically compressed DRG (CCD) injury model. Extracellular recordings from teased dorsal root microfilaments demonstrated that acute topical application of TNF-α to the DRG for 15 min evoked C- and Aβ-fiber responses in both normal and CCD rats. However, the response latency was significantly shorter, and the peak discharge rate was higher, in CCD fibers than in normal fibers. Intracellular recordings from small- and large-sized neurons showed that TNF-α induced greater depolarization and greater decrease in rheobase in CCD neurons than in normal neurons. The proportion of both small- and large-sized neurons that were responsive to TNF-α increased significantly after CCD injury. Furthermore, TNF-α altered the discharge patterns of large, spontaneously active neurons in addition to enhancing their discharge rates. However, the depolarization caused by TNF-α in such neurons was minor (<2 mV). Inflammatory cytokines such as TNF-α increased the sensitivity of sensory neurons in normal and CCD rats. The CCD injury itself, on the other hand, increased neuronal responses to inflammatory cytokines.
Anti-Inflammatory and Chondroprotective Effect of TSG-6 (Tumor Necrosis Factor-α-Stimulated Gene-6) in Murine Models of Experimental Arthritis