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P75 NEUROTROPHIN RECEPTOR (P75NTR) MODULATES THE NGF SIGNALING PATHWAY RATHER THAN TROPOMYOSIN‐RELATED KINASE A (TRKA) IN RAT DISCOGENIC PAIN MODELS: GP99.

Orita, Sumihisa; Nagata, Maiko; Horii, Manato; Yamashita, Masaomi; Yamauchi, Kazuyo; Inoue, Gen; Suzuki, Munetaka; Eguch, Yawara; Kamoda, Hiroto; Arai, Gen; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Suzuki, Miyako; Morinaga, Tatsuo; Ohtori, Seiji; Takahashi, Kazuhisa

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Spine Journal Meeting Abstracts: October 2010 - Volume - Issue - p 241
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INTRODUCTION: Nerve growth factor (NGF) has been reported to cause discogenic pain by inducing abnormal nerve ingrowth into degenerative discs. NGF has two receptors: a high affinity tropomyosin‐related kinase A (TrkA) and a low affinity p75 neurotrophin receptor (p75NTR). The NGF‐TrkA complex has been reported to play a primary role in transmitting inflammatory pain. However, their involvement in discogenic pain is unclear. The present study aimed to investigate the role of these receptors in a rat discogenic low back pain model.

METHODS: Twenty‐eight female Sprague Dawley rats were equally divided into four groups: control, puncture, anti‐TrkA, and anti‐p75. In the groups except for the control group, the L5–L6 intervertebral disc was exposed and injured by repeated puncture, and then neurotracer Fluoro‐Gold (FG) and appropriate agents were applied: sterilized saline for the puncture group, anti‐TrkA antibody for the anti‐TrkA group, and anti‐p75NTR antibody for the anti‐p75 group. In the control group only FG was applied into the uninjured disc. Lumbar DRGs were harvested and immunostained for the inflammatory pain marker calcitonin related‐gene peptide (CGRP). The expression of CGRP in the DRG neurons was investigated.

RESULTS: FG‐labeled DRG neurons were observed in all the DRGs with a dominant population in L1 and L2 DRGs. In FG‐labeled CGRP‐ir DRG neurons innervating discs, CGRP expression was elevated in all the injured‐disc groups compared with the control group, while the expression in the two antibody‐treated groups was significantly decreased compared with the puncture group (P < 0.05). Furthermore, the expression was significantly lower in the anti‐p75NTR group than in the anti‐TrkA group (P < 0.05).

DISCUSSION: The elevated CGRP expression in the DRGs innervating injured rat discs suggests a pathogenesis for discogenic low back pain. Decreased CGRP expression by p75NTR inhibition suggests the possibility of a more crucial role of p75NTR than TrkA in discogenic pain pathogenesis.

© 2010 Lippincott Williams & Wilkins, Inc.