Transient Receptor Potential (TRP) channels are multifunctional sensory molecules that are abundant in the skin and are involved in the sensory pathways of itch, pain, and inflammation. In this review article, we explore the complex physiology of different TRP channels, their role in modulating itch sensation, and their contributions to the pathophysiology of acute and chronic itch conditions. We also cover small molecule and topical TRP channel agents that are emerging as potential anti-pruritic treatments; some of which have shown great promise, with a few treatments advancing into clinical trials—namely, TRPV1, TRPV3, TRPA1, and TRPM8 targets. Lastly, we touch on possible ethnic differences in TRP channel genetic polymorphisms and how this may affect treatment response to TRP channel targets. Further controlled studies on the safety and efficacy of these emerging treatments is needed before clinical use.
Chronic pain and chronic pruritus are both debilitating conditions that cause a significant burden to patients. Oxidative stressdriven by an imbalance between reactive oxygen species and antioxidants-has been shown to play a role both in pain disorders and conditions in which chronic itch is a prominent symptom. Antioxidants can be useful in treating oxidative stress-driven diseases and have shown promise in treating chronic pain conditions such as fibromyalgia and osteoarthritis. However, their role in treating pruritus and pruritic conditions such as psoriasis and atopic dermatitis remains unclear. Many of the current treatments for chronic itch are costly, associated with side effects, and have limited efficacy. Therefore, further controlled studies exploring antioxidants as a potential therapeutic option for chronic pruritus are warranted.
Chronic spontaneous urticaria (CSU) is a condition in which wheals, angioedema, and pruritus occur spontaneously and recurrently for at least 6 weeks. The etiology of this disease is partially dependent on production of autoantibodies that activate and recruit inflammatory cells. Although the wheals can resolve within 24 h, symptoms have a significant detrimental impact on the quality of life of these patients. Standard therapy for CSU includes second-generation antihistamines and omalizumab. However, many patients tend to be refractory to these therapies. Available treatments such as cyclosporine, dapsone, dupilumab, and tumor necrosis factor alpha (TNFa) inhibitors have been used with success in some cases. Furthermore, various biologics and other novel drugs have emerged as potential treatments for this condition, and many more are currently under investigation in randomized clinical trials.
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