Novel TRPM8 agonist cooling compound against chronic itch: results from a randomized, double-blind, controlled, pilot study in dry skin.

BACKGROUND: Patients suffering from chronic pruritus (CP) due to dry skin with are often applying emollients containing menthol. However, topical menthol may be irritating and of weak potency in severe pruritus. Two TRPM8 agonists, (1R,2S,5R)-N-(2-(2-pyridinyl)ethyl)-2-ispropyl-5-methylcyclohexancarboxamide and menthoxypropanediol, combined as cooling compound (CC) have shown stronger activation of TRPM8 than menthol. OBJECTIVES: Objective of this study was to evaluate the efficacy and safety of CC in alleviating pruritus in patients with dry itchy skin. METHODS: In this vehicle-controlled, double-blind, randomized (1 : 1) study, 70 dry skin patients with pruritus intensity measured by Numerical Rating Scale (NRS) ≥3, were treated twice daily over 4 weeks, either with a lotion containing CC or with its vehicle. RESULTS: At treatment end, pruritus, assessed by a global score, improved significantly more in the CC than in the vehicle group (79.2% vs. 47.1%; P < 0.05; primary endpoint). Also assessed by verbal rating scale (VRS) and percentual improvement, pruritus decreased significantly more in the CC group (P = 0.007/P = 0.015) compared to vehicle arm after treatment. Up to 84% of CC-treated patients reported a significant, sometimes too strong, long-lasting cooling effect. The health-related quality of life improved significantly more in the CC group (P = 0.023). Skin roughness, dryness and hydration improved significantly in both groups without significant differences in-between them. There were no severe adverse events reported. CONCLUSIONS: Treatment of dry and pruritic skin with a lotion containing the TRPM8 agonist combination ameliorates severe pruritus and represents a possible novel treatment for the burdensome symptom. The most suitable treatment concentration needs still to be identified. ClinicalTrials.gov: NCT00669708.

[Clinical features and prurigo nodularis in nephrogenic pruritus]. / Klinische Charakteristika und Prurigo nodularis bei nephrogenem Pruritus.

BACKGROUND: Nephrogenic pruritus (NP) is a well-known associated symptom in patients with chronic renal failure. The aim of the present study was to make a detailed dermatological analysis including distribution of excoriations and their correlation with pruritus characteristics. PATIENTS AND METHODS: Data on a total of 17 patients with NP (14 males, mean 65.4 ± SD 14.3 years) were subjected to retrospective analysis. Most of the patients developed NP after start of kidney disease; however, in 20 % of the patients, there was premonitory appearance of the symptom 18 months (median) earlier. A majority of patients reported neuropathic symptom qualities (burning, stinging). In 94.1 % of patients xerosis was present; in 58.8 %, prurigo nodularis. The latter group of patients had a longer duration of pruritus as well as up to 10 years longer duration of renal disease than those without prurigo. RESULTS: Pruritus characteristics of NP show a wide variance without a clear profile that is useful for clinical diagnosis. NP can occur premonitorily, and, if of long duration and with coexistent metabolic diseases, can develop into prurigo.

Brief treatment of children's dental pain and anxiety.

Pain interferes with children's dental care, but anxiety and pain are often confounded. We tested a classical-conditioning model of dental pain with 45 8- to 11-yr.-old children but found little support for it. Instead, different treatments for pain were effective in reducing the children's expectations of discomfort. Expected discomfort may be the most important part of dental pain, so expectations might well be the focus of such treatments.

Motivational deficit in depressed cancer patients.

A motivational theory of depression states that depression consists of low expectations and low values for rewards. This theory accurately describes one class of depression, the affective disorders. The present study tested its accuracy for another class of depression, adjustment disorder with depressed mood. This class of depression is precipitated by environmental stresses, such as chronic illness. The focus was therefore on people (N = 48) who were experiencing terminal cancer and nonterminal cancer. Results supported each prediction generated by the motivational theory. The cancer patients exhibited low expectations and low values; hence, they were unmotivated and depressed. Implications are that some of the symptoms exhibited by cancer patients may be manifestations of negative beliefs rather than physical impairments.