Hemodialysis-Related Pruritus: A Double-Blind, Placebo-Controlled, Crossover Study of Capsaicin 0.025% Cream

Abstract

Pruritus is a significant symptom among patients receiving hemodialysis. However, its underlying mechanisms remain obscure. Substance P, a neuropeptide, has been implicated in the mediation of pain and some itch sensations. Local application of capsaicin depletes the peripheral neurons of substance P and may block the conduction of pain or pruritus. This study aims to assess the efficacy and safety of capsaicin 0.025% cream in the treatment of hemodialysis-related pruritus and to further explore the underlying pathomechanism. Nineteen hemodialysis patients with idiopathic, moderate (n = 5) to severe (n = 14) pruritus were examined in a double-blind, placebo-controlled, crossover study and 17 of them completed the study. Topical agent of capsaicin or placebo base cream was applied to localized areas of pruritus 4 times a day. The severity of pruritus and treatment-related side effects (cutaneous burning/stinging sensations, dryness, or erythema) were evaluated weekly. The results showed (1) that 14 of 17 patients reported marked relief and 5 of these 14 patients had complete remission of pruritus during capsaicin treatment (Wilcoxon signed-ranks test, 2p < 0.001); (2) capsaicin was significantly more effective than placebo (Mann-Whitney rank sum test, 2p < 0.001) and a prolonged antipruritic effect was observed 8 weeks posttreatment; (3) no serious side effects were noted during the study and (4) there were no significant changes in serum concentrations of albumin, calcium, phosphorus, alkaline phosphatase, or intact parathyroid hormone during the treatment with either capsaicin or placebo. In summary, the present study indicates indirectly that idiopathic pruritus in some patients on maintenance hemodialysis may be transmitted by substance P from the peripheral sensory neurons to the central nervous system. Topical capsaicin with the unique pharmacological effect is demonstrated to markedly improve the pruritus of these patients.

HbA1c Is Related with Uremic Pruritus in Diabetic and Nondiabetic Hemodialysis Patients

“…16,28 Additionally, as uremia progresses, peripheral nervous system becomes more affected, especially the sensory parts. 21 On the other hand, reports showing the efficacy of lidocaine, 29 capsaicin, [30][31][32] and gabapentin 33,34 in controlling UP are in favor of a relationship between neuropathy and pruritus in HD patients. Thus, we can only hypothesize that even in nondiabetic patients, disturbed glucose metabolism as demonstrated by higher HbA1c levels, at least by inducing permissive role for the development of neuropathy, may result in increased sensation of itching.…”

Recent Advances in Treatment for Uremic Pruritus

“…Further, Tarng et al [40] reported that 19 HD patients with idiopathic, moderate (n = 5) to severe (n = 14) pruritus were examined in a double-blind, placebo-controlled, crossover study, and 17 of them completed the study. Topical capsaicin or placebo base cream was applied to localized areas of pruritus 4 times a day.…”

Uremic pruritus – a review

“…Proteases are pruritogenic substances and protease receptors have been described in the distal end of C fibers. Stimulation of these release substance P. Capsaicin inhibits substance P and inturn itching [25,26]. CKD associated pruritus patients also have neuropathy which is relieved with gabapentin [27].…”

“…Capsaicin desensitizes the nociceptive nerve endings depletes the substance P in peripheral neurons and blocks the pain of pruritus. Side effect like burning sensation sometimes may make the patient to stop using it [26,47]. Similarly pramoxine based anti-itch lotion which is also a local anesthetic agent has reduced pruritus significantly.…”