Role of TNF-alpha in sensitization of nociceptive dorsal horn neurons induced by application of nucleus pulposus to L5 dorsal root ganglion in rats.
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-alpha (TNF-alpha), a third group received autologous NP plus local soluble TNF-alpha receptor type 1 (0.013 microg) which binds TNF-alpha to prevent its action. In each group, neuronal responses to graded heat (38-50 degrees 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-alpha 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-alpha 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.
Cuellar
M J
MJ
Section of Neurobiology, Physiology and Behavior, University of California, 1 Shields Avenue, Briggs Hall, Davis, CA 95616, USA 1650 Lead Hill Blvd. #100, Roseville, CA 95661, USA.
Montesano
X P
XP
Carstens
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E
D000818:Animals; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000502:physiology*; D008159:Lumbar Vertebrae / Q000502:physiology; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D020671:Posterior Horn Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha