Functional connectivity impairment of thalamus-cerebellum-scratching neural circuits in pruritus of chronic spontaneous urticaria

Abstract

Pruritus of chronic spontaneous urticaria (CSU) is one of the most common and irritating sensations that severely affects the quality of life. However, the changes in the functional connectivity (FC) between thalamic subregions and other brain regions have not been fully elucidated. This study aimed to explore the potential changes in brain neural circuits by focusing on various subregions of the thalamus in patients with CSU pruritus to contribute to the understanding of chronic pruritus from the perspective of central mechanisms. A total of 56 patients with CSU and 30 healthy controls (HCs) completed the data analysis. Urticaria Activity Score 7 (UAS7), pruritus visual analog score (VAS-P), Dermatological Life Quality Index (DLQI), and immunoglobulin E (IgE) values were collected to assess clinical symptoms. Seed-based resting-state functional connectivity (rs-FC) analysis was used to assess relevant changes in the neural circuits of the brain. Compared to HCs, seeds within the caudal temporal thalamus (cTtha) on the right side of patients with CSU showed increased rs-FC with the cerebellum anterior lobe (CAL). Seeds within the lateral prefrontal thalamus (lPFtha) on the right side showed increased rs-FC with both CAL and pons, while those within the medial prefrontal thalamus (mPFtha) on the right side showed increased rs-FC with both CAL and the dorsal lateral prefrontal cortex (dlPFC) on the right side. Seeds within the posterior parietal thalamus (PPtha) on the right side showed increased rs-FC with the cerebellum posterior lobe (CPL) on the left side. The UAS7 values and IgE levels were positively correlated with the rs-FC of the right dlPFC. Our results suggest that patients with CSU may exhibit stronger rs-FC alterations between certain thalamic subregions and other brain regions. These changes affect areas of the brain involved in sensorimotor and scratching.Trial registration number[http://www.chictr.org.cn], identifier [ChiCTR1900022994].

Higher‐order sensorimotor circuit of the whole‐brain functional network involved in pruritus regulation in atopic dermatitis

“…Its dorsomedial portion encompasses the supplementary motor area (SMA), one of the nodes in the motor control networks 29 . The activation of the SFG in response to pruritus induced by external stimuli has been observed in numerous neuroimaging studies, 12,31–33 even in the absence of scratching 16,34 . As the SMA also mediates the inhibition of motor plans to enhance motor control, 35 the negative correlation between SCORAD scores and DC values of the LSFG in AD participants may be related to weakened motor inhibition, leading to a reduced ability to control the urge to scratch.…”

Itch: from the skin to the brain – peripheral and central neural sensitization in chronic itch

“…Compared with healthy controls, the left fusiform cortex in CSU patients demonstrated significantly decreased functional connectivity with the right orbitofrontal cortex, medial prefrontal cortex, premotor cortex, primary motor cortex, and the cerebellum, and increased functional connectivity with the right posterior insular cortex, primary somatosensory cortex, and secondary somatosensory cortex. Other CSU imaging studies have reported decreased resting state functional connectivity between the right ventral striatum and the right occipital cortex, and between the right putamen and left precentral gyrus, as well as changes in resting-state functional connectivity between thalamic regions and other brain areas associated with sensorimotor function and scratching ( Wang et al, 2018 ; Zhang L. et al, 2022 ).…”

“…Brain imaging studies of chronic itch patients are limited, although current studies show a trend of structural and functional differences in sensory and motor-related brain regions when compared to healthy individuals ( Jin and Wang, 2019 ; Najafi et al, 2020 ). Furthermore, imaging studies of chronic itch with fMRI demonstrate an overlap in brain regions with chronic pain indicating that central sensitization mechanisms are likely to be similar ( Harte et al, 2018 ; Wang et al, 2018 ; Zhang L. et al, 2022 ).…”