Dorsal root sensitivity to interleukin-1 beta, interleukin-6 and tumor necrosis factor in rats.
The release of inflammatory cytokines caused by a disrupted disc may play a critical role in pain production at nerve endings, axons, and nerve cell bodies. Herniated disc tissue has been shown to release inflammatory cytokines such as interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor (TNF), and other algesic chemicals. This study was designed to characterize the effects of these proinflammatory cytokines on the somatosensory neural response at the dorsal root level in rats. It is hypothesized that their effects on nerve endings in disc and adjacent tissue contribute to low-back pain, and the effects on dorsal root axons and ganglia contribute to radiculopathy and sciatica. Surgically isolated sacral dorsal roots were investigated by electrophysiologic techniques. IL-1beta, IL-6, or TNF (100 ng, each) were applied onto the dorsal roots. Neural responses and mechanosensitivity of the receptive fields were evaluated over time. The results showed that 3 h after each cytokine application, the neural activity was statistically decreased. The mechanical sensitivity of the receptive fields increased at 90 min following IL-1beta or TNF application, and returned to normal more than 3 h after IL-1beta application. IL-1beta, IL-6, and TNF may be neurotoxic to dorsal root axons. Furthermore IL-1beta and TNF may sensitize the peripheral receptive fields. This study suggests that dorsal roots may be impaired by these proinflammatory cytokines.
Ozaktay
A Cüneyt
AC
Wayne State University, Bioengineering Center, 818W Hancock, Detroit, MI 48201, USA. ozaktay@wayne.edu
Cavanaugh
John M
JM
Asik
Ibrahim
I
DeLeo
Joyce A
JA
Weinstein
James N
JN
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D007405:Intervertebral Disc Displacement / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017116:Low Back Pain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D011843:Radiculopathy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012585:Sciatica / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D014110:Touch / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha