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. 2024 Jan-Dec:20:17448069241254455.
doi: 10.1177/17448069241254455.

A novel anti-pruritic: Topical co-administration of high molecular weight hyaluronan (HMWH) with protamine, a transdermal transport enhancer

Paul G Green  1   2 , Jon D Levine  1   3
Affiliations

A novel anti-pruritic: Topical co-administration of high molecular weight hyaluronan (HMWH) with protamine, a transdermal transport enhancer

Paul G Green et al. Mol Pain. 2024 Jan-Dec.

Abstract

Pruritis, the sensation of itch, is produced by multiple substances, exogenous and endogenous, that sensitizes specialized sensory neurons (pruriceptors and pruri-nociceptors). Unfortunately, many patients with acute and chronic pruritis obtain only partial relief when treated with currently available treatment modalities. We recently demonstrated that the topical application of high molecular weight hyaluronan (HMWH), when combined with vehicles containing transdermal transport enhancers, produce potent long-lasting reversal of nociceptor sensitization associated with inflammatory and neuropathic pain. In the present experiments we tested the hypothesis that the topical formulation of HMWH with protamine, a transdermal transport enhancer, can also attenuate pruritis. We report that this topical formulation of HMWH markedly attenuates scratching behavior at the nape of the neck induced by serotonin (5-hydroxytryptamine, 5-HT), in male and female rats. Our results support the hypothesis that topical HMWH in a transdermal transport enhancer vehicle is a strong anti-pruritic.

Keywords: 5-hydroxytryptamine; Hyaluronan; itch; topical anti-pruritic; transdermal transporter.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Topical HMWH attenuates 5-HT-induced scratching behavior in male and female rats. Rats received an intradermal (i.d.) injection of 5-HT, alone or after topically administered HMWH dissolved in protamine-containing vehicle. Data are presented here as cumulative number of scratches. Topical hyaluronan in a transdermal transport enhancer vehicle, protamine, markedly attenuated the number of 5-HT-induced scratches in both female and male rats (one-tailed paired Student’s t-test, females: p < .0001; males: p < .0004); all groups n = 6.
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