The functional and structural alterations of the striatum in chronic spontaneous urticaria

Abstract

The brain has long been known to be the regulation center of itch, but the neuropathology of chronic itch, such as chronic spontaneous urticaria (CSU), remains unclear. Thus, we aimed to explore the brain areas involved in the pathophysiology of CSU in hopes that our results may provide valuable insights into the treatment of chronic itch conditions. 40 CSU patients and 40 healthy controls (HCs) were recruited. Urticaria activity scores 7 (UAS7) were collected to evaluate patient's clinical symptoms. Amplitude of low frequency fluctuations (ALFF), voxel-based morphometry (VBM), and seed-based resting-state functional connectivity (rs-FC) analysis were used to assess brain activity and related plasticity. Compared with HCs, CSU patients exhibited 1) higher ALFF values in the right ventral striatum / putamen, which were positively associated with clinical symptoms as measured by UAS7; 2) gray matter volume (GMV) increase in the right ventral striatum and putamen; and 3) decreased rs-FC between the right ventral striatum and the right occipital cortex and between the right putamen and the left precentral gyrus. Using multiple-modality brain imaging tools, we demonstrated the dysfunction of the striatum in CSU. Our results may provide valuable insights into the neuropathology and development of chronic itch.Chronic spontaneous urticaria (CSU) is a common disorder characterized by the spontaneous eruption of short-lived (<24 h) itchy wheals, with or without angioedema, for a period longer than 6 weeks 1 . CSU affects 0.5-1.0% of the population at any given time and severely diminishes the quality of life of patients 2,3 . Despite its prevalence, there is a lack of understanding of the pathology of CSU and consequently, limited treatment options. Standard therapy with regular doses of non-sedating second-generation H1 antihistamines (H1AH) are ineffective for more than 50% of patients with CSU 2 .Accumulating evidence suggests that the skin and brain are functionally connected 4,5 . For instance, the brain shares numerous mediators with skin through the hypothalamic-pituitary-adrenal axis (HPA axis) 4 . Studies have shown that the HPA axis may be altered in stress-related skin diseases, resulting in the activation of mast cells 6,7 , which are the primary effector cells in CSU 8 .The most common clinical manifestation of CSU is repeated itching and scratching. Studies suggest that the brain plays a key role in the itch-scratch cycle 9 . Functional brain imaging studies have identified brain regions associated with the itch-scratch cycle, such as the primary somatosensory cortex (SI), secondary somatosensory cortex (SII), primary motor cortex (MI), premotor cortex (PM), supplementary motor area (SMA), cerebellum, the prefrontal cortex (PFC), the striatum, and thalamus [10][11][12][13][14] .In recent years, resting-state functional magnetic resonance imaging (rs-fMRI) has been applied to investigate the intrinsic functional organization of the brain [15][16][17] . There are many resting-state fMRI data analysis methods,...

Functional and anatomical brain connectivity in psoriasis patients and healthy controls: a pilot brain imaging study after exposure to mentally induced itch

“…Other studies have observed changes in grey matter caused by chronic pruritus in end‐stage renal disease 42 and chronic spontaneous urticaria 3 . Therefore, changes in the white matter structure are not surprising if interconnected regions also exhibit structural modifications in the grey matter.…”

“…Other studies have observed changes in grey matter caused by chronic pruritus in end-stage renal disease 42 and chronic spontaneous urticaria. 3 Therefore, changes in the white matter structure are not surprising if interconnected regions also exhibit structural modifications in the grey matter. Connectivity analysis showed that a large network was significantly more interconnected in the psoriasis patient group than in the healthy control group, while all nodes in this network are activated in itch.…”

“…The brain networks that are responsible for pain and itch are similar but distinct 1,2 . Recent studies have shown that the brains of patients with chronic pruritus, such as chronic spontaneous urticaria or atopic dermatitis, process itch in a different manner than healthy subjects, 3–5 as previously observed with pain 6–9 . Clinical trials of psoriasis treatments have increasingly focused on itch, 10 but itch processing in psoriasis patients is poorly understood.…”

The Dysfunction of the Cerebellum and Its Cerebellum-Reward-Sensorimotor Loops in Chronic Spontaneous Urticaria

“…In addition, we also found that the rs-FC between the cerebellum and brain regions associated with reward and sensorimotor processing were significantly altered, and these results are consistent with previous neuroanatomy studies, as well as a recent study from our group using the same data set. We found that compared with controls, CSU patients exhibited higher amplitude of low frequency fluctuations (ALFF) values in the right ventral striatum/putamen and increased gray matter volume in the right ventral striatum and putamen [ 42 ].…”

Addiction and the itch‐scratch cycle. What do they have in common?

“…Most evidence of impulsive to compulsive shift comes from classic animal studies on addiction, suggesting a shift from ventral to more dorsal domains of the striatum in animals with compulsive drug use . However, activation and increased grey matter density of the ventral striatum was reported in chronic itch patients . Although the ventral striatum may play an important role in modulation of chronic itch condition, it is unclear whether ventral‐to‐dorsal shift occurs in chronic itch condition.…”