Antipruritic Effect of Topical Acetaminophen Gel in Histaminergic and Non-histaminergic Itch Provocation: A Double-blind, Vehicle-controlled Pilot Study

Authors

  • Leigh A. Nattkemper Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami Miller School of Medicine, 33136 Miami, FL, USA
  • Kaining Zhi
  • Kaeli E. Romero
  • Serena M. Shah
  • Teresa Ju
  • Kayla Fourzali
  • Rachel Shireen Golpanian
  • Flor MacQuhae
  • Yiong Huak Chan
  • David B. Lebo
  • Gil Yosipovitch

DOI:

https://doi.org/10.2340/00015555-3910

Keywords:

pruritus, antipruritic, acetaminophen, itch model, topical therapy

Abstract

There is a need for new topical antipruritics that are effective on many types of itch. This study examined the antipruritic efficacy of a new formulation of topical acetaminophen. In vitro skin permeability studies showed that 2.5% and 5% formulations are able to rapidly deliver an adequate amount of the drug into the skin. In a double-blind, vehicle-controlled, randomized study in 17 healthy volunteers, 1%, 2.5% and 5% acetaminophen gels and a vehicle gel were applied to the skin prior to histaminergic and non-histaminergic itch induction and assessment of thermal pain thresholds. The 2.5% and 5% gel formulations significantly reduced the itch intensity time course and the area under the curve for both histamine and cowhage itch. No effect was noted on heat pain thresholds and no adverse effects were observed. These results suggest that topical acetaminophen would be a safe and effective over-the-counter medication for itch.

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References

Fourzali K, Golpanian RS, Yosipovitch G. Emerging drugs for the treatment of chronic pruritic diseases. Expert Opin Emerg Drugs 2020; 25: 273-284.

https://doi.org/10.1080/14728214.2020.1801632 DOI: https://doi.org/10.1080/14728214.2020.1801632

Greaves MW, McDonald-Gibson W. Itch: role of prostaglandins. Br Med J 1973; 3: 608-609.

https://doi.org/10.1136/bmj.3.5881.608 DOI: https://doi.org/10.1136/bmj.3.5881.608

Kassis V, SØndergaard J. Heat separation of normal human skin for epidermal and dermal prostaglandin analysis. Arch Dermatol Res 1982; 273: 301-306.

https://doi.org/10.1007/BF00409259 DOI: https://doi.org/10.1007/BF00409259

Papoiu AD, Tey HL, Coghill RC, Wang H, Yosipovitch G. Cowhage-induced itch as an experimental model for pruritus. A comparative study with histamine-induced itch. PLoS One 2011; 6: e17786.

https://doi.org/10.1371/journal.pone.0017786 DOI: https://doi.org/10.1371/journal.pone.0017786

Andersen HH, Sørensen A-KR, Nielsen GAR, Mølgaard MS, Stilling P, Boudreau SA, et al. A test-retest reliability study of human experimental models of histaminergic and non-histaminergic itch. Acta Derm Venereol 2017; 97: 198-207.

https://doi.org/10.2340/00015555-2502 DOI: https://doi.org/10.2340/00015555-2502

Saglam G, Gunduz O, Ulugol A. Blockade of cannabinoid CB1 and CB2 receptors does not prevent the antipruritic effect of systemic paracetamol. Acta Neurol Belg 2014; 114: 307-309.

https://doi.org/10.1007/s13760-013-0272-9 DOI: https://doi.org/10.1007/s13760-013-0272-9

Hawro T, Fluhr JW, Mengeaud V, Redoulès D, Church MK, Maurer M, et al. Polidocanol inhibits cowhage - but not histamine-induced itch in humans. Exp Dermatol 2014; 23: 922-923.

https://doi.org/10.1111/exd.12555 DOI: https://doi.org/10.1111/exd.12555

Yosipovitch G, Ademola J, Lui P, Amin S, Maibach HI. Topically applied aspirin rapidly decreases histamine-induced itch. Acta Derm Venereol 1997; 77: 46-48.

Papoiu AD, Valdes-Rodriguez R, Nattkemper LA, Chan YH, Hahn GS, Yosipovitch G. A novel topical formulation containing strontium chloride significantly reduces the intensity and duration of cowhage-induced itch. Acta Derm Venereol 2013; 93: 520-526.

https://doi.org/10.2340/00015555-1564 DOI: https://doi.org/10.2340/00015555-1564

Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A. The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors. Eur J Pharmacol 2006; 531: 280-281.

https://doi.org/10.1016/j.ejphar.2005.12.015 DOI: https://doi.org/10.1016/j.ejphar.2005.12.015

Klinger-Gratz PP, Ralvenius WT, Neumann E, Kato A, Nyilas R, Lele Z, et al. Acetaminophen relieves inflammatory pain through CB1 cannabinoid receptors in the rostral ventromedial medulla. J Neurosci 2018; 38: 322-234.

https://doi.org/10.1523/JNEUROSCI.1945-17.2017 DOI: https://doi.org/10.1523/JNEUROSCI.1945-17.2017

Nattkemper LA, Tey HL, Valdes-Rodriguez R, Lee H, Mollanazar NK, Albornoz C, et al. The genetics of chronic itch: gene expression in the skin of patients with atopic dermatitis and psoriasis with severe itch. J Invest Dermatol 2018; 138: 1311-1317.

https://doi.org/10.1016/j.jid.2017.12.029 DOI: https://doi.org/10.1016/j.jid.2017.12.029

Valdes-Rodriguez R, Kaushik SB, Yosipovitch G. Transient receptor potential channels and dermatological disorders. Curr Top Med Chem 2013; 13: 335-343.

https://doi.org/10.2174/15680266112129990090 DOI: https://doi.org/10.2174/15680266112129990090

Eberhardt MJ, Schillers F, Eberhardt EM, Risser L, de la Roche J, Herzog C, et al. Reactive metabolites of acetaminophen activate and sensitize the capsaicin receptor TRPV1. Sci Reports 2017; 7: 1-18.

https://doi.org/10.1038/s41598-017-13054-3 DOI: https://doi.org/10.1038/s41598-017-13054-3

Tiippana E, Hamunen K, Kontinen V, Kalso E. The effect of paracetamol and tropisetron on pain: experimental studies and a review of published data. Basic Clin Pharmacol Toxicol 2013; 112: 124-131.

https://doi.org/10.1111/j.1742-7843.2012.00935.x DOI: https://doi.org/10.1111/j.1742-7843.2012.00935.x

Ramachandran A, Jaeschke H. Acetaminophen hepatotoxicity. Semin Liver Dis 2019; 39: 221-234.

https://doi.org/10.1055/s-0039-1679919 DOI: https://doi.org/10.1055/s-0039-1679919

Leheup BF, Ducousso S, Picard S, Alluin R, Goetz C. Subcutaneous administration of paracetamol - good local tolerability in palliative care patients: an observational study. Palliat Med 2018; 32: 1216-1221.

https://doi.org/10.1177/0269216318772472 DOI: https://doi.org/10.1177/0269216318772472

Published

2022-01-31

How to Cite

Nattkemper, L. A., Zhi, K., Romero, K. E., Shah, S. M., Ju, T., Fourzali, K., … Yosipovitch, G. (2022). Antipruritic Effect of Topical Acetaminophen Gel in Histaminergic and Non-histaminergic Itch Provocation: A Double-blind, Vehicle-controlled Pilot Study. Acta Dermato-Venereologica, 102, adv00640. https://doi.org/10.2340/00015555-3910