Plasticity in Brainstem Mechanisms of Pain Modulation by Nicotinic Acetylcholine Receptors in the Rat

Overview

Journal eNeuro

Specialty Neurology

Date 2017 Feb 16

PMID 28197544

Citations 8

Authors

Francis J Jareczek

Stephanie R White

Donna L Hammond

Affiliations

Soon will be listed here.

Abstract

Individuals with chronic pain may be driven to smoke more because the analgesic efficacy of nicotine diminishes. To determine whether persistent pain diminishes the actions of a nicotinic acetylcholine receptor (nAChR) agonist in pain modulatory pathways, we examined the effects of epibatidine in the rostral ventromedial medulla (RVM) of rats with and without inflammatory injury induced by intraplantar injection of complete Freund's adjuvant (CFA). In uninjured rats, epibatidine produced a dose-dependent antinociception that was completely blocked by dihydro-β-erythroidine (DHβE; α4β2 antagonist) and partially blocked by methyllycaconitine (MLA; α7 antagonist). Epibatidine reversed heat hyperalgesia when microinjected in the RVM 4 h, 4 d, or 2 weeks after CFA treatment. Although DHβE completely blocked epibatidine's antihyperalgesic effect at 4 h, at 2 weeks it elicited only partial antagonism. Methyllycaconitine was ineffective at both time points. Epibatidine's antinociceptive efficacy in the uninjured hind paw progressively declined, and it was without effect 2 weeks after CFA. Moreover, as early as 4 h after CFA, the antinociceptive effect of epibatidine was no longer antagonized by DHβE. Neither antagonist alone altered paw withdrawal latency in uninjured or CFA-treated rats, suggesting that neither α4β2 nor α7 nAChRs are tonically active in the RVM. The and of α4β2 nAChRs in the RVM were unchanged after CFA treatment. These observations provide the first evidence of pharmacological plasticity of the actions of α4β2 nAChR agonists in a critical brainstem pain modulatory pathway and may in part explain why people with chronic pain smoke more than the general population.

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