Exogenous tumor necrosis factor-alpha induces abnormal discharges in rat dorsal horn neurons.
METHODS
An electrophysiologic study to examine effects of exogenous application of tumor necrosis factor-alpha (TNF-alpha ) activities and nociresponses of dorsal horn neurons in the spinal cord at L5.


OBJECTIVE
To investigate the role of TNF-alpha in the induction and development of hyperalgesia in neural mechanisms responsible for a radicular pain.


BACKGROUND
TNF-alpha is found in the herniated disc and known to play a pivotal role in the development of inflammatory hyperalgesia; however, it is not known whether TNF-alpha causes abnormal discharge in the dorsal horn neurons and enhances nociresponse.


METHODS
Single-unit activities of neurons in the L5 superficial dorsal horn were extracellularly recorded, using 28 urethane-anesthetized rats. The wide dynamic range and nociceptive-specific neurons activated by stimulation of the hind paw were selected. Effects of exogenous TNF-alpha were examined regarding 1) spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) responses of wide dynamic range neurons to noxious stimulation, and 3) morphologic changes in the dorsal root ganglion.


RESULTS
Application of TNF-alpha to the nerve root induced 1) a significant increase in spikes/sec in spontaneous discharges of wide dynamic range and nociceptive-specific neurons, 2) enhanced responses of wide dynamic range neurons to noxious stimulation, and 3) inflammatory changes in the ganglion.


CONCLUSIONS
These results suggest the possibility that TNF-alpha produced in the vicinity of nerve roots due to disc herniation might cause ectopic discharges in primary afferent fibers and thereby induce the prolonged excitation in pain-processing neurons responsible for radicular pain.
Onda
Akira
A
Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. aonda@fmu.ac.jp
Hamba
Michiko
M
Yabuki
Shoji
S
Kikuchi
Shinichi
S
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004333:Drug Administration Routes; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004558:Electric Stimulation; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D006614:Hindlimb / Q000294:innervation / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology*; D008161:Lumbosacral Region; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha