NGF-induced hyperexcitability causes spontaneous fluctuations of intracellular Ca2+ in rat nociceptive dorsal root ganglion neurons.
NGF is a candidate for a pathogenic mediator of neuropathic pain after nerve injury and inflammation. It has been reported that adult rat dorsal root ganglion (DRG) neurons cultured in the presence of NGF at 100 ng/ml generate spontaneous action potentials. However, it is unclear what types of subpopulation of DRG neurons are affected by NGF and how the intracellular Ca(2+) concentration ([Ca(2+)](i)) changes in such neurons. To elucidate these points, we measured [Ca(2+)](i) in adult rat DRG neurons cultured with or without NGF. [Ca(2+)](i) fluctuated spontaneously in the absence of any stimuli in subpopulations of NGF-treated neurons, but such fluctuations were not observed in all NGF-untreated neurons. NGF-induced [Ca(2+)](i) fluctuations were inhibited by decreases in extracellular Na(+) concentration, TTX and Lidocaine, suggesting that spontaneous action potentials provoked the [Ca(2+)](i) fluctuation. NGF-induced [Ca(2+)](i) fluctuation was observed in small and medium sized neurons and in Capsaicin-sensitive neurons more frequently than in Capsaicin-non-responsive neurons. These results suggest that NGF acted on the nociceptive neurons and made them hyperexcitable to generate spontaneous action potentials and spontaneous [Ca(2+)](i) fluctuations. The [Ca(2+)](i) fluctuation induced by NGF may play some role in the regulation of membrane excitability of nociceptive sensory neurons and neuropathic pain.
Ozaki
Yui
Y
Department of Veterinary Physiology, Faculty of Agriculture, Tottori University, 101, South 4th, Koyama, Tottori 6808553, Japan.
Kitamura
Naoki
N
Tsutsumi
Atsushi
A
Dayanithi
Govindan
G
Shibuya
Izumi
I
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D048429:Cell Size; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects* / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology
D020932:Nerve Growth Factor; D012964:Sodium; D011188:Potassium; D002211:Capsaicin