Bidirectional effects of serum TNF alpha level and spinal p38MAPK phosphorylation on hyperalgesia variation during...

Regarding the role of TNFα in the induction of hyperalgesia, the dual suggested roles of the Pp38 MAPK intracellular pathway in the emergence of symptomatic inflammation, we aimed to investigate the bidirectional effects of serum TNFα level and p38 MAPK phosphorylation on hyperalgesia variation during different stages of adjuvant-induced arthritis. Hyperalgesia and edema were assessed at 0, 3, 7, 14, and 21 days of study after arthritis induction by CFA. Anti-TNFα and Pp38 inhibitor were administered during the 21 days of study. Receptor and intra-cellular enzyme expression were detected by western blotting. Anti-TNFα administration in the AA group decreased paw volume and hyperalgesia until the 14th day of study; on the 21st day, those symptoms increased. Daily administration of anti-TNFα antibody caused significant decrease in spinal mOR protein and Pp38/p38 MAPK enzyme level expression on the 14th and 21st days compared to the AA control group. Our data suggested that phosphorylation of spinal p38 MAPK enzyme played an important role in bidirectional effects of serum TNFα on inflammatory symptoms via spinal mOR expression variation.