Elevation of Tumor Necrosis Factor Alpha in Dorsal Root Ganglia and Spinal Cord is Associated with Neuroimmune Modulation of Pain in an Animal Model of Multiple Sclerosis

Abstract

Neuropathic pain (NPP) is a frequently reported symptom described by 50-80% of multiple sclerosis (MS) patients. Although Th1 cell activation is known to drive the pathology of MS, this critical step has also been suggested to be involved in the neuroimmune induction of NPP. The release of pain inducing inflammatory cytokines such as tumour necrosis factor alpha (TNFα) from activated Th1 cells may have key implications in the development of MS-induced pain. We hypothesize that immune mediated antigenic induction of inflammatory cytokines such as TNFα within dorsal root ganglia (DRG) and spinal cord (SC) facilitate the cellular events underlying induction of pain. A rat experimental autoimmune encephalomyelitis (EAE) model of MS was utilized to identify the cellular source and expression changes of TNFα protein and mRNA in the DRG and SC. The TNFα levels in the DRG and SC were correlated with the behavioral testing indicative of NPP. We show significant increases in TNFα protein and mRNA expression in DRG and SC of EAE animals at 12days post induction (EAE12) relative to naïve control (NC) and active control (AC) groups. Further, we show increased TNFα protein and mRNA expression at the dorsal root entry point, which suggests the anterograde transport of both protein and mRNA. Further, the onset of NPP coincides with increased TNFα expression in the SC. These results demonstrate that the elevated expression of TNFα in the DRG and SC may be associated with the pathological induction of NPP in an animal model of MS.