Inflammation-induced increase in nicotinic acetylcholine receptor current in cutaneous nociceptive DRG neurons from the adult rat. (22nd January 2015)

• Record Type: Journal Article
• Authors: Zhang, X.-L.; Albers, K.M.; Gold, M.S.
• Is Part Of: Neuroscience. Volume 284(2015)
• Page Start: 483
• Page End: 499
• Publication Date: 2015-01-22
• Subjects: AITC allyl isothiocyanate -- ANOVA analysis of variance -- Cap capsaicin -- CFA complete Freund's adjuvant -- DiI 1, 1′-dioctadecyl-3, 3, 3′, 3′-tetramethylindocarbocyanine perchlorate -- DMSO dimethyl sulfoxide -- DRG dorsal root ganglion -- EGTA ethylene glycol tetraacetic acid -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- Hex hexamethonium -- IB4 isolectin B4 -- Mec mecamylamine -- MLA methyllycaconitine citrate -- nAChR nicotinic acetylcholine receptor -- TRPA1 transient receptor potential ankyrin type 1; nociceptor sensitization -- inflammatory pain -- ligand-gated ion channel -- voltage-clamp -- current clamp; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2014.10.018
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Nicotine-evoked α7-like and α3β4-like currents are in distinct populations constituting ∼70% of all cutaneous DRG neurons. Nicotine (1 μM) transiently increases α7-like neuron excitability and decreases capsaicin current in α3β4-like neurons. Nicotine (60 μM) transiently increases the excitability of neurons with both α7-like and α3β4-like current. Inflammation alters the distribution and increases the density of α3β4-like and α7-like currents in cutaneous neurons. The impact of nicotine on pain and hypersensitivity will depend on both concentration and timing of acetylcholine release. 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.