Neuropathic Pain in Animal Models of Nervous System Autoimmune Diseases
BACKGROUND Inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) are pleiotropic molecules with widespread action in autoimmune diseases. OBJECTIVE This study characterizes the distribution of iNOS and TNF-alpha in the spinal nerve roots, dorsal root ganglia and sciatic nerve of Lewis rats during experimental autoimmune neuritis (EAN). METHODS Macrophages and neutrophils were identified by immunofluorescence as cellular sources of iNOS and TNF-alpha at various stages of EAN induced by synthetic peptide 26. RESULTS As the disease progressed, iNOS- and TNF-alpha-bearing cells gradually infiltrated the cauda equina, dorsal root ganglia, Th12-L3 spinal roots, and the sciatic nerve. A severer EAN profile developed when more iNOS- and TNF-alpha-bearing cells were present, and the recovery from EAN was related to the disappearance of these cells and the regeneration of nerve fibers. CONCLUSIONS This is the first report to show iNOS- and TNF-alpha-immunoreactive cells in dorsal root ganglia during EAN, suggesting an underlying pathology for the neuropathic pain behavior in EAN. Our results suggest that the cells bearing iNOS and TNF-alpha in the different parts of the peripheral nervous system are involved in the development of the clinical signs observed at each stage of EAN.