Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus

Momose, Akishi; Yabe, Micihihiro; Chiba, Shigetoshi; Kumakawa, Kenjirou; Shiraiwa, Yasuo; Mizukami, Hiroki

doi:10.3390/medicines6040110

Cited by 9 publications

(19 citation statements)

References 35 publications

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“…This is particularly the case for patients on dialysis who frequently suffer from uremic itch, with about 40% of patients with end-stage renal disease being afflicted with moderate to severe pruritus [ 15 ]. In this context it is interesting to note that Cav3.2 channel expression is upregulated in the skin of uremic itch patients (presumably in nerve endings) [ 16 ], hinting at a possible role of these channels in uremic itch pathology. While we did not examine mouse models of chronic pruritus here, there is accumulating evidence that Cav3.2 channels are involved in the development of histamine and non-histamine dependent itch in rodents.…”

Section: Resultsmentioning

confidence: 99%

Ethosuximide inhibits acute histamine- and chloroquine-induced scratching behavior in mice

Gadotti

Zamponi

2021

Mol Brain

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We have recently reported that the Cav3.2 T-type calcium channel which is well known for its key role in pain signalling, also mediates a critical function in the transmission of itch/pruritus. Here, we evaluated the effect of the clinically used anti-seizure medication ethosuximide, a well known inhibitor of T-type calcium channels, on male and female mice subjected to histaminergic- and non-histaminergic itch. When delivered intraperitoneally ethosuximide significantly reduced scratching behavior of mice of both sexes in response to subcutaneous injection of either histamine or chloroquine. When co-delivered subcutaneously together with either pruritogenic agent ethosuximide was also effective in inhibiting scratching responses in both male and female animals. Overall, our results are consistent with an important role of Cav3.2 T-type calcium channels in modulating histamine-dependent and histamine-independent itch transmission in the primary sensory pathway. Our findings also suggest that ethosuximide could be explored further as a possible therapeutic for the treatment of itch.

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Section: Resultsmentioning

confidence: 99%

Ethosuximide inhibits acute histamine- and chloroquine-induced scratching behavior in mice

Gadotti

Zamponi

2021

Mol Brain

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“…They found a significantly elevated expression of Cav3.2, BKCa, and anoctamin1, and reduced expression of TRPV1 in CKD-aP patients. They concluded that these changes in expression of ion channels in CKD patients might increase generator potential related to itching [ 31 ].…”

Section: Etiopathogenesismentioning

confidence: 99%

Chronic Kidney Disease-Associated Pruritus

Agarwal

Garg²,

Karagaiah

et al. 2021

Toxins

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Pruritus is a distressing condition associated with end-stage renal disease (ESRD), advanced chronic kidney disease (CKD), as well as maintenance dialysis and adversely affects the quality of life (QOL) of these patients. It has been reported to range from 20% to as high as 90%. The mechanism of CKD-associated pruritus (CKD-aP) has not been clearly identified, and many theories have been proposed to explain it. Many risk factors have been found to be associated with CKD-aP. The pruritus in CKD presents with diverse clinical features, and there are no set features to diagnose it.The patients with CKD-aP are mainly treated by nephrologists, primary care doctors, and dermatologists. Many treatments have been tried but nothing has been effective. The search of literature included peer-reviewed articles, including clinical trials and scientific reviews. Literature was identified through March 2021, and references of respective articles and only articles published in the English language were included.

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“…Chronic kidney disease-associated pruritus CKD-aP is thought to involve an alteration in nerve fibers and increased amounts of circulating pruritogens such as uremic toxins, which also stimulate reactive oxygen species (ROS) [26]. One study sought to further understand how the interact between uremic toxins and nerve fibers in patients with CKD-aP resulted in itch [27]. Momose et al obtained skin biopsies from the forearm and elbow of two cohorts of patients.…”

Section: Pathophysiologymentioning

confidence: 99%