Reply

Abstract

We appreciate the interesting comments by Dr Kwatra.1Kwatra S.G. Role of neurokinin-1 receptor in artemin-induced warmth-provoked pruritus.J Allergy Clin Immunol. 2013; 131: 928Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Indeed, we also hoped that the identification of the function of artemin, a substance P (SP)–inducible neurotrophic factor, in skin would lead to new effective therapies for intractable warmth-provoked pruritus, especially if mechanisms to regulate the adverse effect of artemin through decreasing its expression could be found. As Dr Kwatra pointed out, blockade of neurokinin-1 receptor (NK1R) offers therapeutic potential for such cases of pruritus. To provide a better understanding of our study,2Murota H. Izumi M. Abd El-Latif M.I.A. Nishioka M. Terao M. Tani M. et al.Artemin causes hypersensitivity to warm sensation, mimicking warmth-provoked pruritus in atopic dermatitis.J Allergy Clin Immunol. 2012; 130: 671-682.e4Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar we offer further information about the artemin-inducible concentration of SP. In our in vitro study SP increased the expression of artemin mRNA (see Fig 1, C, in Murota et al2Murota H. Izumi M. Abd El-Latif M.I.A. Nishioka M. Terao M. Tani M. et al.Artemin causes hypersensitivity to warm sensation, mimicking warmth-provoked pruritus in atopic dermatitis.J Allergy Clin Immunol. 2012; 130: 671-682.e4Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). Artemin mRNA expression levels in the presence of SP at 1 × 10−6 or 1 × 10−4 mol/L were statistically different than control levels, as determined by means of 1-way ANOVA and the Bonferroni multiple comparison test. A low concentration (1 × 10−10 mol/L) of SP also significantly increased the expression of artemin mRNA compared with that seen in untreated control subjects according to the results of an unpaired t test (artemin/glyceraldehyde-3-phosphate dehydrogenase ratios [mean ± SD] in the 1 × 10−10 mol/L SP-treated and control groups, 0.26 ± 0.07 and 0.62 ± 0.16, respectively; P = .0001). SP was dissolved before use to avoid degradation. Thus we conclude that relatively low concentrations of SP had an effect on the increased expression of artemin in vitro. Although we did not examine the involvement of NK1R in the SP-mediated increase in expression of artemin in vitro and in vivo, this interesting issue will be the subject of future investigations, especially in light of the availability of an NK1R inhibitor, as Dr Kwatra mentioned in his comment. Role of neurokinin-1 receptor in patients with artemin-induced warmth-provoked pruritusJournal of Allergy and Clinical ImmunologyVol. 131Issue 3PreviewI read with great interest the study by Murota et al1 implicating a role for artemin, which is released by dermal fibroblasts in response to substance P (SP), in patients with warmth-provoked pruritus. The authors suggest that artemin might be a novel target for treating pruritic skin disorders, particularly atopic dermatitis. Although the authors have extensively studied the interplay between artemin, SP, and end-stream peripheral nerve sprouting, the role of neurokinin-1 receptor (NK1R), the main physiologic target of SP,2 remains unexplored. Full-Text PDF