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 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.

α‐Conotoxins active at α3‐containing nicotinic acetylcholine receptors and their molecular determinants for selective inhibition

“…Given that α3‐containing nAChRs, including the α3β4 subtype, are predominantly expressed in nociceptive DRG neurons (Fucile et al, ; Spies et al, ), it suggests that this subtype may be involved in neuronal signalling of nociception and inflammation. A recent electrophysiological study on cutaneous rat DRG neurons showing that inflammation induces an increase in current density of slow nicotine‐evoked currents is consistent with the involvement of α3/β4‐containing nAChRs (Zhang et al, ). Furthermore, in cultured mouse sympathetic neurons and adrenal chromaffin cells, α3‐containing nAChRs were identified as key components for the hyperglycaemia‐induced inactivation of nAChR‐mediated currents.…”

Cholinergic Nociceptive Mechanisms in Rat Meninges and Trigeminal Ganglia: Potential Implications for Migraine Pain

“…This is consistent with data from other tissues, such as skin or nasal epithelium, where nicotine can directly activate nociceptive nerve endings (36, 47–50). …”

A review of current theories and treatments for phantom limb pain

“…DRG soma express receptors for acetylcholine (56), glutamate (57,58), and GABA (59) in quantities sufficient to have strong neuromodulatory effects on sensory signaling. The receptors' presence raises two issues.…”