ABSTRACT
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 AND RESULTS: Intraperitoneal 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 α7 nAChR full agonists PHA543613 and PNU282987 was failed to block stretching and CPA behaviour induced by AA. However, the α7 nAChR-positive allosteric modulator PNU120596 blocked AA-induced CPA in a dose-dependent manner without reducing stretching behaviours. CONCLUSIONS: Our data revealed that while nonselective 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, 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 α7 nAChRS in the negative affective, but not sensory, component of visceral pain. SIGNIFICANCE: The present results suggest that allosteric modulation of α7 nAChR may provide new strategies in affective aspects of nociception.
ABSTRACT
This study examined relationships of stress (negative event frequency during the last year) to reports of illness among 92 children, aged 10 to 13 years. Children's health status was reported separately by children and parents, and children's skill in identifying and communicating their feelings was tested for direct and buffering relationships on illness reports. Analyses controlled for demographics and negative affect of both children and parents, and children's verbal ability was also tested for confounding. Results showed that stress correlated positively with children's poor health, whether the children's health status was reported by children or by parents. Children's emotional skill was correlated with better health when health was reported by children, but with worse health when health was reported by parents. Further, moderator analyses indicated that the relationship between negative event frequency and children's poor health as reported by parents held only for children with high levels of skill in identifying and communicating feelings. These findings suggest that negative life events impair children's health, but that the health reports of children and parents are quite different, and parents' views may be affected by children's skill in communicating their internal states.