The Anterior Insula and its Projection to the Prelimbic Cortex are Involved in the Regulation of 5-HT-Induced Itch
Juan Yao1,2 · Xuan Li1 · Guang‑Yan Wu1 · Bing Wu1 · Jun‑Hui Long3 · Pu‑Jun Wang3 · Shu‑Lei Liu3 · Jie Gao4 · Jian‑Feng Sui1,21 Experimental Center of Basic Medicine, Army Medical University, Chongqing 400038, China
2 Department of Physiology, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China
3 Department of Dermatology, The 958th Army Hospital of the People’s Liberation Army, Chongqing 400020, China
4 State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical Centre of the PLA, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing 400042, China
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 subcortical 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 photometry 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 neurons, or selective inhibition of the activity of glutaminergic 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. However, 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, pharmacogenetic 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.
Keywords
Itch · Insular cortex; Prelimbic cortex; Conditioned place aversion; Pharmacogenetic inhibition
