{'fraction_non_alphanumeric': 0.0323242688558235, 'fraction_numerical': 0.004104669061056952, 'mean_word_length': 5.701030927835052, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Nicotinic receptor modulation of primary afferent excitability with selective regulation of Aδ-mediated spinal actions.

Somatosensory input strength can be modulated by primary afferent depolarization (PAD) generated via presynaptic GABAA receptors on afferent terminals. We investigated whether acetylcholine (ACh) also provides modulatory actions on PAD via nicotinic acetylcholine receptors (nAChRs) using in vitro murine spinal cord nerve-attached models. Primary afferent stimulation-evoked dorsal root potentials (DRPs) were used as an indirect measure of PAD while evoked afferent transmission was recorded in the deep dorsal horn as extracellular field potentials (EFPs). Changes in afferent membrane excitability were inferred from DC-shifts in recorded dorsal roots or peripheral nerves. Of nAChR antagonists tested, D-tubocurarine (D-TC) depressed DRP amplitude the most (43% of control) and actions were restricted to the A-fiber-evoked DRP and selective depression of Aδ-evoked synaptic EFPs (36% of control). These actions occurred centrally as afferent excitability was unchanged. In comparison, ACh depressed evoked responses by different mechanisms. ACh produced coincident depolarizing DC-shifts in peripheral axons and intraspinally that corresponded temporally with reductions in the DRP and all afferent-evoked synaptic actions (31-37% of control). DC-shifts were produced via nAChRs on primary afferents: they were also seen with nAChR agonists (epibatidine and nicotine), blocked with D-TC but not GABAA receptor blockers, and retained after block of voltage-gated Na+ channels. Notably, prominent actions on evoked responses were comparably altered between two mouse strains, in rat, and when performed in different labs. Thus, nAChRs can regulate afferent excitability via two distinct mechanisms: by modulating central Aδ-afferent actions, and by broadly changing membrane polarization of all classes of primary afferents.