Leukemia inhibitory factor differentially regulates capsaicin and heat sensitivity in cultured rat dorsal root ganglion neurons.
Thermal hyperalgesia is one hallmark of neuropathic pain conditions. Although the exact pathophysiological mechanisms remain elusive, nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are considered key mediators. Their local availability or synthesis are altered by nerve damage and, in turn, they entail changes in phenotype of affected neurons. We examined the effects of LIF on capsaicin sensitivity, heat responsiveness, and galanin immunoreactivity in rat dorsal root ganglion neurons cultured for up to 6 days without supplemented NGF. Using double labeling, the proportions of heat-sensitive/galanin-immunoreactive (GAL-IR) and capsaicin-sensitive/GAL-IR neurons were compared over time in culture with galanin immunoreactivity being a marker for nociceptive neurons. The time course of the proportions of neurons responding to heat (44 degrees C) or capsaicin (1 microM) which also were GAL-IR was differently affected by LIF. In the absence of LIF, within the population of heat-sensitive neurons, the proportion of neurons also GAL-IR increased from 17% to 32% between 6h and 1 day in culture to stay at this level. For the capsaicin-sensitive neurons, the proportion of neurons also GAL-IR increased from 10% after 6h to 18% at day 2 and then decreased to 4% at day 4. In contrast, LIF prevented the increase in the proportion of heat-sensitive/GAL-IR neurons and the decrease of capsaicin-sensitive/GAL-IR neurons. The results suggest that LIF partially prevents TRPV-1 downregulation in NGF-deprived nociceptive galaninergic DRG neurons. Furthermore, there is evidence that LIF regulates the expression of a heat receptor distinct from TRPV-1.
Engert
Sabine
S
Department of Obstetrics and Gynecology, University of Würzburg, 97080 Würzburg, Germany.
Wendland
Jens R
JR
Schwab
Albrecht
A
Petersen
Marlen
M
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002478:Cells, Cultured; D019004:Galanin / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000378:metabolism
D053605:Leukemia Inhibitory Factor; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D019004:Galanin; D020932:Nerve Growth Factor; D002211:Capsaicin