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Pharmacological Inhibition of Tumor Necrosis Factor May Reduce Pain Behavior Changes Induced by Experimental Disc Puncture in the Rat: An Experimental Study in Rats

Nakamae, Toshio MD*,†; Ochi, Mitsuo MD, PhD; Olmarker, Kjell MD, PhD*

doi: 10.1097/BRS.0b013e3181d8bef3
Basic Science

Study Design. Pain behavior assessment in rats following disc puncture (DP) and simultaneous tumor necrosis factor (TNF) inhibition.

Objective. To assess if treatment with TNF inhibition could reduce the pain behavior changes induced by DP in the rat.

Summary of Background Data. Anular tears with leakage of nucleus pulposus have been suggested to be one possible cause of low back pain (LBP). In an experimental model, it was recently shown that DP might induce specific pain behavior changes. The aim of the present study was to a study if inhibition of TNF might reduce such pain behavior changes.

Methods. Sixty rats underwent facetectomy and puncture of the fourth lumbar disc. The rats were simultaneously treated with doxycycline locally at 0.3 and 3.0 mg/kg and systemically at 3.0 mg/kg, or infliximab locally at 0.5 and 5.0 mg/kg, and systemically at 5.0 mg/kg, (n ∇ 10 for each subseries). The rats were videotaped at 1, 3, 7, 14, and 21 days after surgery. The videos were analyzed regarding presence of wet-dog shakes (WDS). Data from a previous study with sham surgery and DP without treatment were included for comparison.

Results. All groups treated with doxycycline resulted in a statistically significant reduction of WDS compared to the group without treatment (DP). In infliximab treated animals, WDS decreased with statistically significance compared to the nontreated DP group at all analyzed days except for the group with high dose local treatment where a statistically significant reduction was obtained only at days 14 and 21.

Conclusion. The present study showed that TNF inhibition induced a marked reduction of wet dog shakes. It is not fully understood if wet-dog shakes may relate to LBP, but in view of recent clinical findings one may consider clinical studies of TNF inhibition for the treatment of LBP.

TNF inhibition markedly reduced pain behavior changes induced by disc puncture in the rat. In view of recent clinical studies on TNF inhibition of sciatica with a simultaneous reduction of Low Back Pain, one might consider clinical studies also for the treatment of Low Back Pain with TNF inhibition.

From the *Department of Medical Chemistry and Cell Biology, Musculoskeletal Research, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

Address correspondence and reprint requests to Kjell Olmarker, MD, PhD, Department of Medical Chemistry and Cell Biology, Musculoskeletal Research, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE–405 30 Gothenburg, Sweden; E-mail: kjell.olmarker@gu.se

Acknowledgment date: November 9, 2009. Acceptance date: February 6, 2010.

The device(s)/drug(s) that is/are the subject of this manuscript is/are not FDA-approved for this indication and is/are not commercially available in the United States.

Foundation funds were received in support of this work. Yes, benefits in some form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. One or more of the author(s) has/have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript, e.g., royalties, stocks, stock options, decision making position.

Supported by the Swedish Research Council grants (521–2007–2956), the Gothenburg Medical Society, AFA Insurance, the Gothenburg Medical Society, the Ollie and Elof Ericsson Foundation for Scientific Research, Stiftelsen Olle Engkvist byggmästare and the Felix Neubergh Foundation.

© 2011 by Lippincott Williams & Wilkins