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THE EFFECT OF IκB KINASE (IKKB) INHIBITION ON LUMBAR VERTEBRAL DISC HERNIATION IN A RAT MODEL: GP9.

Hirosawa, Naoya; Ishikawa, Tetsuhiro; Miyagi, Masayuki; Ohtori, Seiji; Inoue, Gen; Eguchi, Yawara; Kamoda, Hiroto; Arai, Gen; Suzuki, Miyako; Kubota, Gou; Sakuma, Yoshihiro; Oikawa, Yasuhiro; Takahashi, Kazuhisa

Spine Journal Meeting Abstracts: October 2011 - Volume - Issue - [no page #]
GENERAL POSTERS
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Chiba University, Department of Orthopedic Surgery, Chiba city, Japan

INTRODUCTION: Radicular pain is a common symptom of lumbar disc herniation (LDH). Given that it is induced by many inflammatory cytokines, pain cannot be controlled by inhibiting an individual cytokine. Recent reports suggest that Nuclear Factor‐kappa B (NF‐κB) and an IκB kinase‐beta (IKKβ) protein complex may regulate inflammatory cytokines. Thus, this study investigated the effects of IKKβ inhibition on pain behavior and calcitonin gene‐related peptide (CGRP: painful neuropeptide) expression in dorsal root ganglion (DRG) neurons.

METHODS: For the LDH model, the right sciatic nerve was exposed and the nucleus pulposus (NP) was harvested from amputated tails. The sciatic nerve was then pinched and NP was applied. IKKβ inhibitor was applied to the sciatic nerve in the LDH+IKKβ group. Nerve exposure and tail amputation without pinch and NP application was performed in the control group. Mechanical allodynia was measured for 2 weeks. Seven days post‐surgery, DRGs were sectioned and immunostained; CGRP‐immunoreactive neurons were classified as either small (<30μm in diameter) or large (>30μm).

RESULTS: Significantly more mechanical allodynia and more CGRP‐immunoreactive neurons were observed in the LDH group compared with control. However, application of IKKβ inhibitor significantly reduced pain behavior and the number of CGRP‐immunoreactive neurons. The size‐distribution pattern of CGRPimmunoreactive neurons shifted from small to large cells in the LDH group. However, there were fewer small and large CGRP‐immunoreactive cells in the LDH+IKKβ groups.

DISCUSSION: CGRP is not produced in large neurons under physiologic conditions, however, in this study CGRP expression was shifted to large neurons after nerve injury. This change in cell‐size distribution suggests that the CGRP expression in large neurons is related to neuropathic pain in LDH. Our results indicate that IKKβ inhibitor might be effective at improving radiculopathy induced by LDH.

© 2011 Lippincott Williams & Wilkins, Inc.