Abstract
Itch is an unpleasant sensation that urges people and animals to scratch.Neuroimaging studies on itch have yielded extensive correlations with diverse cortical and sub-cortical regions,including the insular lobe.However,the role and functional specificity of the insular cortex(IC)and its subdivisions in itch mediation remains unclear.Here,we demonstrated by immunohistochemistry and fiber photom-etry tests,that neurons in both the anterior insular cortex(AIC)and the posterior insular cortex(PIC)are activated during acute itch processes.Pharmacogenetic experiments revealed that nonselective inhibition of global AIC neu-rons,or selective inhibition of the activity of glutaminer-gic neurons in the AIC,reduced the scratching behaviors induced by intradermal injection of 5-hydroxytryptamine(5-HT),but not those induced by compound 48/80.How-ever,both nonselective inhibition of global PIC neurons and selective inhibition of glutaminergic neurons in the PIC failed to affect the itching-scratching behaviors induced by either 5-HT or compound 48/80.In addition,pharmacoge-netic inhibition of AIC glutaminergic neurons effectively blocked itch-associated conditioned place aversion behavior,and inhibition of AIC glutaminergic neurons projecting to the prelimbic cortex significantly suppressed 5-HT-evoked scratching.These findings provide preliminary evidence that the AIC is involved,at least partially via aversive emotion mediation,in the regulation of 5-HT-,but not compound 48/80-induced itch.
基金项目
National Natural Science Foundation of China(82271542)
Natural Science Foundation of Chongqing(cstc2020jcyjmsxm X0391)
Natural Science Foundation of Chongqing(cstc2019jcyjmsxm X0269)
Chongqing Medical Scientific Research Project(Joint project of Chongqing Health Commission and Science and Technology Bureau(2023ZDXM001)