BACKGROUND: Preclinical assays of affective and sensorial aspects of nociception play a key role in research on both the neurobiology of pain and the development of novel analgesics. Therefore, we investigated the effects of nicotine and alpha-7 nicotinic acetylcholine receptor (nAChR) modulators in the negative affective and sensory components of visceral pain in mice.
METHODS & RESULTS: Intraperitoneal acetic acid (AA) administration resulted in a robust stretching behavior and conditioned place aversion (CPA) in mice. We observed a dose-dependent reduction of AA-induced stretching and CPA by the non-selective nAChRs agonist nicotine. Mecamylamine, a non-selective nAChRs agonist, was able to block its effects, however, hexamethonium, a peripherally-restricted non-selective nicotinic antagonist, was able to block nicotine's effect on stretching behavior but not on CPA. In addition, systemic administration of α7 nAChR full agonists PHA543613 and PNU282987 were failed to block stretching and CPA behavior induced by AA. However, the α7 nAChR positive allosteric modulator PNU120596 blocked AA-induced CPA in a dose-dependent manner without reducing stretching behaviors.
CONCLUSIONS: Our data revealed that while non-selective nAChR activation induces antinociceptive properties on the sensorial and affective signs of visceral pain in mice, α7 nAChRS activation has no effect on these responses. In addition, non-selective nAChR activation induced antinociceptive effect on stretching behavior was mediated by central and peripheral mechanisms. However, the effect of non-selective nAChR activation on CPA was mediated centrally. Furthermore, our data suggest a pivotal role of allosteric modulation of α7 nAChRS in the negative affective, but not sensory, component of visceral pain. This article is protected by copyright. All rights reserved.