Effect of nicotine and alpha-7 nicotinic modulators on visceral pain-induced conditioned place aversion in mice

BackgroundPreclinical 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 and ResultsIntraperitoneal acetic acid (AA) administration resulted in a robust stretching behaviour and conditioned place aversion (CPA) in mice. We observed a dose-dependent reduction in AA-induced stretching and CPA by the nonselective nAChRs agonist nicotine. Mecamylamine, a nonselective nAChRs agonist, was able to block its effects; however, hexamethonium, a peripherally restricted nonselective nicotinic antagonist, was able to block nicotine's effect on stretching behaviour but not on CPA. In addition, systemic administration of 7 nAChR full agonists PHA543613 and PNU282987 was failed to block stretching and CPA behaviour induced by AA. However, the 7 nAChR-positive allosteric modulator PNU120596 blocked AA-induced CPA in a dose-dependent manner without reducing stretching behaviours. ConclusionsOur data revealed that while nonselective nAChR activation induces antinociceptive properties on the sensorial and affective signs of visceral pain in mice, 7 nAChRS activation has no effect on these responses. In addition, nonselective nAChR activation-induced antinociceptive effect on stretching behaviour was mediated by central and peripheral mechanisms. However, the effect of nonselective nAChR activation on CPA was mediated centrally. Furthermore, our data suggest a pivotal role of allosteric modulation of 7 nAChRS in the negative affective, but not sensory, component of visceral pain. SignificanceThe present results suggest that allosteric modulation of 7 nAChR may provide new strategies in affective aspects of nociception.