Tumor necrosis factor-Alpha stimulates cytokine expression and transient sensitization of trigeminal nociceptive neurons

Objective: Elevated levels of tumor necrosis factor-alpha (TNF-alpha) in the capsule of the temporomandibular joint (TMJ) are implicated in the underlying pathology of temporomandibular disorders (TMD). TMD are a group of conditions that result in pain in the TMJ and/or muscles of mastication, and are associated with significant social and economic burdens. The goal of this study was to investigate the effect of elevated TNF-alpha levels in the TMJ capsule on nocifensive behavioral response to mechanical stimulation of trigeminal neurons and regulation of cytokines within the trigeminal ganglion. Design: Male Sprague-Dawley rats were injected bilaterally in the TMJ capsule with TNF-alpha and changes in nocifensive head withdrawal responses to mechanical stimulation of cutaneous tissue directly over the capsule was determined using von Frey filaments. Cytokine levels in trigeminal ganglia were determined by protein array analysis at several time points post injection and correlated to nocifensive behavior. Results: TNF-alpha caused a significant increase in the average number of nocifensive responses when compared to naive and vehicle treated animals 2 h post injection, but levels returned to control levels at 24 h. Based on array analysis, the levels of eight cytokines were significantly elevated above vehicle control levels at 2 h following TNF-alpha injection, but all eight had returned to the vehicle control levels after 24 h. Conclusions: Our findings provide evidence that elevated levels of TNF-alpha in the joint capsule, which is reported to occur in TMD, promotes nociception in trigeminal ganglia neurons via a mechanism that temporally correlates with differential regulation of several cytokines. (C) 2016 Elsevier Ltd. All rights reserved.