A Subpopulation of Amygdala Neurons Mediates the Affective Component of Itch

Abstract

Itch consists of both sensory and affective components. For chronic itch patients, the affective component of itch affects both quality of life (leading to psychological comorbidities) and disease prognosis (by promoting scratching of itchy skin). We found that acute itch stimuli, such as histamine, induced anxiety-like behavior and increased activity (c-Fos expression) in the amygdala in adult male C57BL/6 mice. Itch stimuli also increased activity in projection areas to the amygdala, suggesting that these regions form a circuit for affective itch processing. Electrophysiological characterization of histamine-responsive amygdala neurons showed that this population was active on a behaviorally relevant timescale and partially overlapped with pain signaling. Selective optogenetic activation of histamine-responsive amygdala neurons in adult male and female Fos:CreER T2 ;R26 Ai14 mice using the Targeted Recombination in Active Populations system enhanced both scratching and anxiety-like behavior. These results highlight the importance of itch-responsive amygdala neurons in modulating itch-related affect and behavior.The sensation of itch includes an affective component that leads to stress and anxiety in chronic itch patients. We investigated the neuronal basis of affective itch in mice, with a focus on the amygdala, the key brain region for the generation of anxiety. A subpopulation of amygdala neurons responded to itch stimuli such as histamine. Optogenetic activation of histamine-responsive amygdala neurons affected both scratching and anxiety-like behavior. Therefore, this population appears to be important for mediating the affective component of itch.

Central circuit mechanisms of itch

“…Itch, like many other somatosensations, is a complex experience consisting of sensory, emotional and motivational components. Indeed, animal studies have shown that acute pruritic stimuli can induce conditional place aversion (CPA), as well as anxiety-like behaviors, as revealed by the open field test (OFT) and elevated plus maze (EPM) assay, suggesting a negative emotional component of itch sensation [104][105][106] . As indicated by previous human functional imaging studies, multiple brain regions could be involved in processing the affective components of itch sensation 1,2 .…”

Effects of Stress on Itch

“…84,85 In an experiment in mice, histamine, chloroquine, and serotonin induced significant activation of the laterocapsular and medial divisions of the central amygdala, and the basolateral amygdala was activated as well. 86 Furthermore, injection of a gaminobutyric acid agonist into the amygdala has been shown to suppress itch in rats. 87 In another study, stress-aggravated pruritus was evoked by asking patients with neurodermatoses to think about stressful situations before magnetic resonance imaging.…”

Neural similarities and differences between pain and itch: Reception, transmission and modulation

“…多个研究 发现, 压力情境会使慢性瘙痒患者的瘙痒强度增加 [48] . OFT)中小鼠在中心方框的停留时间显著减少 [49] . 这些 结果说明, 杏仁核在压力情景促进痒感受增强的过程 中承担着一定的作用 [50] .…”

“…这些 结果说明, 杏仁核在压力情景促进痒感受增强的过程 中承担着一定的作用 [50] . 因此杏仁核、臂旁核、中扣 带回以及内侧前额叶也许构成了痒的情感维度环路, 驱动了抓挠行为和其他由瘙痒导致的焦虑样行为 [49] .…”