title: Inflammation-induced increase in nicotinic acetylcholine receptor current in cutaneous nociceptive DRG neurons from the adult rat.
abstract: The goals of the present study were to determine (1) the properties of the nicotinic acetylcholine receptor (nAChR) currents in rat cutaneous dorsal root ganglion (DRG) neurons; (2) the impact of nAChR activation on the excitability of cutaneous DRG neurons; and (3) the impact of inflammation on the density and distribution of nAChR currents among cutaneous DRG neurons. Whole-cell patch-clamp techniques were used to study retrogradely labeled DRG neurons from naïve and complete Freund's adjuvant inflamed rats. Nicotine-evoked currents were detectable in ∼70% of the cutaneous DRG neurons, where only one of two current types, fast or slow currents based on rates of activation and inactivation, was present in each neuron. The biophysical and pharmacological properties of the fast current were consistent with nAChRs containing an α7 subunit while those of the slow current were consistent with nAChRs containing α3/β4 subunits. The majority of small diameter neurons with fast current were IB4- while the majority of small diameter neurons with slow current were IB4+. Preincubation with nicotine (1 μM) produced a transient (1 min) depolarization and increase in the excitability of neurons with fast current and a decrease in the amplitude of capsaicin-evoked current in neurons with slow current. Inflammation increased the current density of both slow and fast currents in small diameter neurons and increased the percentage of neurons with the fast current. With the relatively selective distribution of nAChR currents in putative nociceptive cutaneous DRG neurons, our results suggest that the role of these receptors in inflammatory hyperalgesia is likely to be complex and dependent on the concentration and timing of acetylcholine release in the periphery.
authors.affiliation: Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: X-L
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15213, United States; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15213, United States.
authors.forename: K M
authors.initials: KM
authors.lastname: Albers
authors.affiliation: Department of Anesthesiology, University of Pittsburgh, Pittsburgh, PA 15213, United States; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15213, United States. Electronic address: msg22@pitt.edu.
authors.forename: M S
authors.initials: MS
authors.lastname: Gold
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006614:Hindlimb; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D056347:Neuroanatomical Tract-Tracing Techniques; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D018689:Sensory System Agents / Q000494:pharmacology; D012867:Skin / Q000294:innervation*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D018689:Sensory System Agents; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403530:nicotinic receptor alpha3beta4; D009538:Nicotine; D005620:Freund's Adjuvant; D000109:Acetylcholine; D002211:Capsaicin
keywords: current clamp; inflammatory pain; ligand-gated ion channel; nociceptor sensitization; voltage-clamp