Inhibiting Nerve Growth Factor or Its Receptors Downregulates Calcitonin Gene-Related Peptide Expression in Rat Lumbar Dorsal Root Ganglia Innervating Injured Intervertebral Discs

Nerve growth factor (NGF) and its dual structurally unrelated receptors tropomyosin related kinase A (TrkA) or p75 neurotrophin receptor (p75(NTR)) cause the pathogenesis of discogenic pain To investigate the sensory innervation of injured rat lumbar intervertebral disc (IVD) we examined the expression of neuropeptides such as calcitonin gene related peptide (CGRP) at dorsal root ganglia (DRG) by inhibiting NGF or its dual receptors Sprague Dawley rats with multiply punctured L5-L6 IVD were used Six experimental groups were prepared naive, sham control, and four agent treated groups with punctured IVD (vehicle, anti NGF antibody anti TrkA antibody, and anti p75NTR antibody) Retrograde neurotracer Fluoro Gold (FG) was applied together except for the naive group Their lumbar DRG were harvested and immunolabeled for CGRP FG labeled DRG neurons were most prevalent at L1 and L2 DRG, and the proportion of FG labeled CGRP immunoreactive DRG neurons in the vehicle group was significantly elevated (p < 0 05) compared with the sham group while those of antibody treated groups especially in the anti p751(NTR) group significantly decreased compared with the vehicle group (p < 0 05) Direct intradiscal application of antibody to NGF or its receptors suppressed CGRP expression, and p75NTR antagonism induced the most profound suppression (c) 2010 Orthopaedic Research Society Published by Wiley Periodicals Inc J Orthop Res 28 1614-1620, 2010