Genetic enhancement of behavioral itch responses in mice lacking phosphoinositide 3-kinase-gamma (PI3Kg)

Abstract

Phosphoinositide 3-kinases (PI3Ks) are important for synaptic plasticity and various brain functions. The only class IB isoform of PI3K, PI3K gamma, has received the most attention due to its unique roles in synaptic plasticity and cognition. However, the potential role of PI3K gamma in sensory transmission, such as pain and itch has not been examined. In this study, we present the evidence for the first time, that genetic deletion of PI3K gamma enhanced scratching behaviours in histamine-dependent and protease-activated receptor 2 (PAR-2)-dependent itch. In contrast, PI3K gamma-deficient mice did not exhibit enhanced scratching in chloroquine-induced itch, suggesting that PI3K gamma selectively contributes to certain types of behavioal itch response. Furthermore, PI3K gamma-deficient mice exhibited normal acute nociceptive responses to thermal and mechanical noxious stimuli. Behavioral licking responses to intraplantar injections of formalin and mechanical allodynia in a chronic inflammatory pain model (CFA) were also not affected by PI3K gamma gene deletion. Our findings indicate that PI3K gamma selectively contributes to behavioral itching induced by histamine and PAR-2 agonist, but not chloroquine agonist.