Nicotinic AChR in Subclassified Capsaicin-Sensitive and -Insensitive Nociceptors of the Rat DRG

1 Department of Oral Surgery and Diagnostic Sciences, Division of Neurosciences, College of Dentistry, 2 Department of Physiological Sciences, College of Veterinary Medicine, and 3 Department of Neuroscience, College of Medicine and University of Florida McKnight Brain Institute, Gainesville, Florida Submitted 8 June 2004; accepted in final form 4 October 2004 Nociceptive cells of the dorsal root ganglion (DRG) were subclassified, in vitro, according to patterns of voltage-activated currents. The distribution and form of nicotinic ACh receptors (nAChRs) were determined. nAChRs were present on both capsaicin-sensitive and -insensitive nociceptors but were not universally present in unmyelinated nociceptors. In contrast, all A nociceptors (types 4, 6, and 9) expressed slowly decaying nAChR. Three major forms of nicotinic currents were identified. Specific agonists and antagonists were used to demonstrate the presence of 7 in two classes of capsaicin-sensitive, unmyelinated nociceptors (types 2 and 8). In type 2 cells, 7 -mediated currents were found in isolation. Whereas 7 was co-expressed with other nAChR in type 8 cells. These were the only classes in which 7 was identified. Other nociceptive classes expressed slowly decaying currents with 4 pharmacology. Based on concentration response curves formed by nicotinic agonists [ACh, nicotine, dimethyl phenyl piperazinium (DMPP), cytisine] evidence emerged of two distinct nAChR differentially expressed in type 4 ( 3 4 ) and types 5 and 8 ( 3 4 5 ). Although identification could not be made with absolute certainty, patterns of potency (type 4: DMPP > cytisine > nicotine = ACh; type 5 and type 8: DMPP = cytisine > nicotine = ACh) and efficacy provided strong support for the presence of two distinct channels based on an 3 4 platform. Studies conducted on one nonnociceptive class (type 3) failed to reveal any nAChR. After multiple injections of Di-I (1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) into the hairy skin of the hindlimb, we identified cell types 2, 4, 6, 8, and 9 as skin nociceptors that expressed nicotinic receptors. We conclude that at least three nicotinic AChR are diversely distributed into discrete subclasses of nociceptors that innervate hairy skin. Address for reprint requests and other correspondence: B. Cooper, Dept. of Oral Surgery and Diagnostic Sciences, Div. of Neuroscience, Box 100416, JHMC, University of Florida College of Dentistry, Gainesville, FL 32610 (E-mail: Bcoop