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J Neurophysiol (October 13, 2004). doi:10.1152/jn.00591.2004
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Submitted on June 8, 2004
Accepted on October 4, 2004

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

Kristofer K. Rau1, Richard D. Johnson2, and Brian Y. Cooper3*

1 Oral and Maxillofacial Surgery and Diagnostic Sciences, University of Florida, Gainesville, FL, USA
2 Physiological Sciences, University of Florida, Gainesville, FL, USA
3 Neuroscience, University of Florida, Gainesville, FL, USA

* To whom correspondence should be addressed. E-mail: Bcooper{at}dental.ufl.edu.

Abstract Nociceptive cells of the DRG were subclassified, in vitro, according to patterns of voltage activated currents. The distribution and form of nicotinic AChR (nAChR) were determined. nAChR were present on both capsaicin sensitive and capsaicin insensitive nociceptors, but were not universally present in unmyelinated nociceptors. In contrast, all A{delta} 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 {alpha}7 in two classes of capsaicin sensitive, unmyelinated nociceptors (types 2 and 8). In type 2 cells, {alpha}7 mediated currents were found in isolation. Whereas {alpha}7 was co-expressed with other nAChR in type 8 cells. These were the only classes in which {alpha}7 was identified. Other nociceptive classes expressed slowly decaying currents with {beta}4 pharmacology. Based upon concentration response curves formed by nicotinic agonists (ACh, nicotine, DMPP, cytisine) evidence emerged of two distinct nAChR differentially expressed in type 4 ({alpha}3{beta}4) and types 5 and 8 ({alpha}3{beta}4{alpha}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 upon an {alpha}3{beta}4 platform. Studies conducted on one non-nociceptive class (type 3) failed to reveal any nAChR. Following multiple injections of DiI 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 3 nicotinic AChR are diversely distributed into discrete subclasses of nociceptors that innervate hairy skin.




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