Recently we reported that nicotine in vitro at low 1 µM concentration suppresses hyperexcitability of colonic dorsal root ganglia (DRG) (L1-L2) neurons in the dextran sodium sulfate (DSS)-induced mouse model of acute colonic inflammation (1). Here we show that multiple action potential firing in colonic DRG neurons persisted at least for 3 weeks post DSS administration while the inflammatory signs were diminished. Similar to that in DSS-induced acute colitis, bath-applied nicotine (1 µM) gradually reduced regenerative multiple-spike action potentials in colonic DRG neurons to a single action potential in 3 weeks post-DSS neurons. Nicotine (1 µM) shifted the activation curve for tetrodotoxin (TTX)-resistant sodium currents in inflamed colonic DRG neurons (V0.5 changed from -37 to -32 mV) but did not affect TTX-sensitive currents in control colonic DRG neurons. Further, subcutaneous nicotine administration (2 mg/kg b.i.d.) in DSS-treated C57Bl/J6 male mice resulted in suppression of hyperexcitability of colonic DRG (L1-L2) neurons and the number of abdominal constrictions in response to intraperitoneal injection of 0.6% acetic acid. Collectively the data suggest that neuronal nAChR-mediated suppression of hyperexcitability of colonic DRG neurons attenuates reduction of visceral hypersensitivity in DSS mouse model of colonic inflammation.
- dorsal root ganglia
- nicotinic receptor
- Copyright © 2011, American Journal of Physiology- Gastrointestinal and Liver Physiology