The effect of repetitive topical applications of local anesthetics (EMLA) on experimental pain and itch (histaminergic and nonhistaminergic)

Giulia Erica Aliotta, Silvia Lo Vecchio*, Jesper Elberling, Lars Arendt-Nielsen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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The effects of repeated topical applications of local anesthetics are poorly investigated as they may, in addition to analgesia, impact peripheral nerve endings in a cumulative manner. In the present study, the effects of 6 repetitive applications of eutectic mixture of lidocaine (EMLA 2.5% and prilocaine 2.5%) were investigated on experimentally induced pain, histaminergic and nonhistaminergic itch, and neurogenic inflammation.

Four skin areas on the forearms of 24 subjects were randomized to receive 3 hours of application of EMLA or placebo twice a day for 3 consecutive days. After each application, superficial blood perfusion (SBP), mechanical (mechanically evoked itch, mechanical pain threshold, and mechanical pain sensitivity), and thermal sensitivity (warm detection threshold, heat pain threshold, and suprathreshold heat sensitivity) were assessed. After the last application of EMLA/placebo, histamine and cowhage was applied (2 areas each) and itch and pain intensity and SBP were assessed.

After 3 hours of EMLA application, significant mechanical and thermal hypoalgesia were found with no cumulative efficacy over the 3 days. EMLA alone had no effect on SBP. Significantly increased SBP, reduced cowhage-induced itch, but the unaffected histamine-induced itch was found when applying EMLA ahead of histamine and cowhage.

EMLA induced a reduction of mechanical and thermal sensitivity without a cumulative-dose effect. EMLA reduced nonhistaminergic itch and pain but not the experimentally provoked histaminergic itch. Selective action of EMLA on polymodal C-fibers could explain these effects.
Original languageEnglish
Article numbere70
Issue number2
Number of pages8
Publication statusPublished - 1 Apr 2023

Bibliographical note

Funding: Supported by the Center for Neuroplasticity and Pain (CNAP),
Aalborg University. Center for Neuroplasticity and Pain (CNAP)
is supported by the Danish National Research Foundation


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