Pharmacological inhibition of tumor necrosis factor may reduce pain behavior changes induced by experimental disc puncture in the rat: an experimental study in rats

Spine (Phila Pa 1976). 2011 Feb 15;36(4):E232-6. doi: 10.1097/BRS.0b013e3181d8bef3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Behavior, Animal / drug effects*
  • Behavior, Animal / physiology
  • Doxycycline / administration & dosage
  • Doxycycline / pharmacology
  • Drug Therapy, Combination
  • Female
  • Infliximab
  • Injections, Intraperitoneal
  • Intervertebral Disc / drug effects*
  • Intervertebral Disc / physiopathology
  • Intervertebral Disc / surgery
  • Laminectomy / adverse effects
  • Low Back Pain / etiology
  • Low Back Pain / physiopathology
  • Low Back Pain / prevention & control*
  • Pain Measurement / methods
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Puncture / adverse effects
  • Tumor Necrosis Factor-alpha / analysis*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Doxycycline