title: Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation.
abstract: Recently, we reported that nicotine in vitro at a low 1-μM concentration suppresses hyperexcitability of colonic dorsal root ganglia (DRG; L(1)-L(2)) 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 wk 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 wk post-DSS neurons. Nicotine (1 μM) shifted the activation curve for tetrodotoxin (TTX)-resistant sodium currents in inflamed colonic DRG neurons (voltage of half-activation 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 (L(1)-L(2)) neurons and the number of abdominal constrictions in response to intraperitoneal injection of 0.6% acetic acid. Collectively, the data suggest that neuronal nicotinic acetylcholine receptor-mediated suppression of hyperexcitability of colonic DRG neurons attenuates reduction of visceral hypersensitivity in DSS mouse model of colonic inflammation.
authors.affiliation: Dept. of Pharmacology and Toxicology, Virginia Commonwealth Univ., Richmond, VA 23298, USA. gabdrakhmano@vcu.edu
authors.forename: Galya R
authors.initials: GR
authors.lastname: Abdrakhmanova
authors.forename: Minho
authors.initials: M
authors.lastname: Kang
authors.forename: M
authors.initials: M
authors.lastname: Imad Damaj
authors.forename: Hamid I
authors.initials: HI
authors.lastname: Akbarali
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003106:Colon / Q000294:innervation* / Q000473:pathology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology
chemical_list: D015222:Sodium Channels; D009538:Nicotine; D016264:Dextran Sulfate