Role of TNF-alpha in sensitization of nociceptive dorsal horn neurons induced by application of nucleus pulposus to L5 dorsal root ganglion in rats

J. M. Cuellar, P. X. Montesano, Earl Carstens

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66 Scopus citations

Abstract

Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain and paresthesia (sciatica). While traditionally considered the result of mechanical compression of the dorsal root ganglion (DRG) and/or spinal nerve root, recent studies implicate pro-inflammatory mediators released from or evoked by NP, a possibility that was presently investigated. Single-unit recordings were made from L5 wide dynamic range dorsal horn neurons in pentobarbital-anesthetized rats. Autologous NP was harvested from a coccygeal disc and placed onto the exposed L5 DRG. A control group had subcutaneous adipose tissue or saline placed similarly. To test involvement of tumor necrosis factor-α (TNF-α), a third group received autologous NP plus local soluble TNF-α receptor type 1 (0.013 μg) which binds TNF-α to prevent its action. In each group, neuronal responses to graded heat (38-50°C) and mechanical (von Frey filaments 4-76 g) stimuli were recorded prior to and at three successive hourly intervals following each treatment. Responses to noxious heat and mechanical stimuli were significantly enhanced 1 h post-NP and remained elevated thereafter. Thermally and mechanically evoked responses were not significantly affected in control rats or those treated with NP+soluble TNF-α receptor type 1. These results indicate that sensitization of nociceptive spinal neuronal responses develops quickly following exposure of the DRG to NP, and that TNF-α is involved. This electrophysiological model of herniated NP may prove useful in further characterizing the role of inflammatory mediators in hyperalgesia and allodynia resulting from lumbar disc herniation.

Original languageEnglish (US)
Pages (from-to)578-587
Number of pages10
JournalPain
Volume110
Issue number3
DOIs
StatePublished - Aug 2004

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Keywords

  • Dorsal horn
  • Electrophysiology
  • Factor-alpha
  • Nucleus pulposus
  • Radicular pain
  • Sciatica
  • Sensitization
  • Tumor necrosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

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