Role of neuronal nicotinic-acetylcholine receptors in the activation of neurons in trigeminal subnucleus caudalis by nicotine delivered to the oral mucosa.
To characterize the role of neuronal nicotinic acetylcholine receptors (nAChRs) in oral irritation and pain, we employed the method of c-fos immunohistochemistry to map the locations and numbers of brainstem neurons that express the immediate-early gene, c-fos, after application of nicotine to the tongue, either alone or after pretreatment with cholinergic antagonists. Groups of anesthetized rats received the following chemicals delivered bilaterally to the dorsal tongue: (1) 0.9% NaCl followed by nicotine (1%, 61 mM), (2) the nAChR antagonist, mecamylamine 0.1% (= 4.9 mM) followed by nicotine, (3) the muscarinic antagonist atropine (0.1% 1.46 mM) followed by nicotine, (4) atropine (1%, 14.6 mM) followed by nicotine, (5) 0.9% NaCl as a control, and (6) unstimulated controls. Two hours later, animals were perfused with phosphate-buffered saline followed by 4% paraformaldehyde through the aorta. Post-fixed brainstems were cut in 50-micron frozen sections and immunohistochemically processed for fos-like immunoreactivity (FLI). Following application of nicotine, there were significant increases in FLI compared with saline-treated controls in dorsomedial and ventrolateral aspects of the trigeminal caudalis. Pretreatment with either mecamylamine or the high (1%) concentration of atropine significantly reduced nicotine-evoked FLI in these areas, while pretreatment with the low (0.1%) atropine concentration did not significantly affect FLI. These results are consistent with the idea that nicotine activates nAChRs residing on lingual nociceptive fibers, which, in turn, excite neurons in trigeminal caudalis.
Carstens
E
E
Section of Neurobiology, Physiology and Behavior, University of California at Davis 95616, USA. eecarstens@ucdavis.edu
Simons
C T
CT
Dessirier
J M
JM
Carstens
M I
MI
Jinks
S L
SL
D000284:Administration, Oral; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009061:Mouth Mucosa / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D013618:Tachyphylaxis / Q000502:physiology; D014059:Tongue / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D014275:Trigeminal Caudal Nucleus / Q000737:chemistry / Q000166:cytology / Q000502:physiology*
D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D001285:Atropine