Increased sensitivity of sensory neurons to tumor necrosis factor alpha in rats with chronic compression of the lumbar ganglia.
Proinflammatory cytokines may sensitize primary sensory neurons and facilitate development of neuropathic pain processes after peripheral nerve injury. The goal of this study was to determine whether responses of dorsal root ganglion (DRG) neurons to exogenous tumor necrosis factor alpha (TNF-alpha) are altered in a chronically compressed DRG (CCD) injury model. Extracellular recordings from teased dorsal root microfilaments demonstrated that acute topical application of TNF-alpha to the DRG for 15 min evoked C- and Abeta-fiber responses in both normal and CCD rats. However, the response latency was significantly shorter, and the peak discharge rate was higher, in CCD fibers than in normal fibers. Intracellular recordings from small- and large-sized neurons showed that TNF-alpha induced greater depolarization and greater decrease in rheobase in CCD neurons than in normal neurons. The proportion of both small- and large-sized neurons that were responsive to TNF-alpha increased significantly after CCD injury. Furthermore, TNF-alpha altered the discharge patterns of large, spontaneously active neurons in addition to enhancing their discharge rates. However, the depolarization caused by TNF-alpha in such neurons was minor (<2 mV). Inflammatory cytokines such as TNF-alpha increased the sensitivity of sensory neurons in normal and CCD rats. The CCD injury itself, on the other hand, increased neuronal responses to inflammatory cytokines.
Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Baogang
B
Liu
Huiqing
H
Li
Sorin J
SJ
Brull
Jun-Ming
JM
Zhang
D000818:Animals; D002908:Chronic Disease; D004594:Electrophysiology; D005260:Female; D005727:Ganglia, Spinal / Q000503:physiopathology*; D007424:Intracellular Fluid / Q000502:physiology; D008161:Lumbosacral Region; D008839:Microelectrodes; D009408:Nerve Compression Syndromes / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha