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Infliximab Attenuates Immunoreactivity of Brain-derived Neurotrophic Factor in a Rat Model of Herniated Nucleus Pulposus

Onda, Akira, MD, PhD*†; Murata, Yasuaki, MD, PhD*‡; Rydevik, Björn, MD, PhD*; Larsson, Karin, BSc*; Kikuchi, Shinichi, MD, PhD; Olmarker, Kjell, MD, PhD*

doi: 10.1097/01.brs.0000137054.08788.b2
Basic Science
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Study Design. The effect of infliximab, a chimeric monoclonal antibody to TNF-α, on induction of brain-derived neurotrophic factor (BDNF) was examined using an experimental herniated nucleus pulposus (NP) model.

Objectives. To investigate whether treatment of infliximab could attenuate an induction of BDNF, which functions as a modulator of pain, following NP application to the nerve root.

Summary of Background Data. Evidence from basic scientific studies proposes that TNF-α is involved in the development of NP-induced nerve injuries. However, the therapeutic mechanisms of infliximab against pain have not been elucidated experimentally.

Methods. Twenty rats were used in this study. In the test groups, the animals underwent application of NP to the L4 nerve roots and received a single systemic (intraperitoneal) injection of infliximab at the time of surgery (Infli-0 group, n = 5) or at 1 day after operation (Infli-1 group, n = 5). As a control treatment, sterile water was administered intraperitoneally to 5 rats with NP application (NP group) and to 5 sham-operated rats (sham group). On day 3 after surgery, the L4 dorsal root ganglion (DRG) and L4 spinal segment were harvested and assessed regarding BDNF immunoreactivity.

Results. Application of NP induced a marked increase of BDNF immunoreactivity in number in the DRG neurons and within the superficial layer in the dorsal horn compared with the sham group (P < 0.01). Infliximab treatment in the Infli-0 and Infli-1 groups reduced the BDNF induction in both DRG and spinal cord (P < 0.05).

Conclusion. These findings indicate that infliximab attenuates the elevated BDNF levels induced by NP. The present study therefore further indicates the importance of TNF-α in sciatica due to disc herniation and the possible therapeutic use of a TNF-α inhibitor for this condition.

An increase of BDNF immunoreactivity in the DRG and spinal cord was induced by application of nucleus pulposus to the nerve root. Both preoperative and postoperative treatments with infliximab reduced this increase. These data may suggest a therapeutic benefit of a TNF-α inhibitor for sciatica due to lumbar disc herniation.

From the *Department of Orthopaedics, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden; †Department of Orthopaedic Surgery, Fukushima Medical University, School of Medicine, Fukushima, Japan; and ‡Department of Orthopaedics, Chiba University, School of Medicine, Chiba, Japan.

Acknowledgment date: September 8, 2003. Acceptance date: October 6, 2003.

Supported by grants from the Swedish Medical Research Council (8685).

The legal regulatory status of the medical device(s)/drug(s) that is/are the subject of this manuscript is not applicable in my country.

Institutional funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

Address correspondence and reprint requests to Kjell Olmarker, MD, PhD, Department of Orthopaedics, Sahlgrenska University Hospital, Göteborg University, SE-413 45 Göteborg, Sweden; E-mail: kjell.olmarker@orthop.gu.se

© 2004 Lippincott Williams & Wilkins, Inc.