Punctate Administration of Ficin as a human and animal model of non‐histaminergic itch

Abstract

Background Ficin, a cysteine protease derived from fig‐tree latex, has been reported to elicit itch and nociceptive sensations, though quantitative sensory studies are lacking. Cowhage containing the pruritic cysteine Mucunain, on the contrary, has been widely studied as activating polymodal nociceptors and eliciting a histamine‐independent itch. Objectives We tested whether ficin in heat‐inactivated cowhage spicules would elicit itch and nociceptive sensations in humans, and analogous behaviours in mice, which are similar to those evoked by native cowhage, and whether these behaviours in mice were dose‐dependent when ficin was injected intradermally. Methods Human volunteers rated the magnitude of itch and nociceptive sensations evoked by either native cowhage spicules or heat‐inactivated spicules soaked in 1, 10 or 100 mg/mL ficin (0.03, 0.3 and 3 ng of ficin in spicule tip), applied to forearm. In mice, itch‐like scratching and nociceptive‐like wiping were recorded in response to either native cowhage, to heat‐inactivated spicules that were either inactive or contained 100 mg/mL ficin, or to intradermal injections of 1.25, 2.5 or 5 μg/ 5 μL, each treatment applied to the cheek. Results The dose of 100 mg/mL ficin in spicules evoked comparable magnitudes of itch, nociceptive sensations and areas of cutaneous dysesthesia as native cowhage in humans and comparable itch‐like scratching and pain‐like wiping behaviours in mice. But to elicit similar behaviours when injected intradermally in mice a greater amount of ficin (1.25 μg) was required. Conclusion Spicule delivery or intradermal injection of ficin elicits behaviours in mice that model itch and nociceptive sensations in humans, suggesting that ficin may be useful in translating mechanistic research on the neural mechanisms of pruritic and nociceptive effects of cysteine proteases between the two species.

Comparative Analysis of the Immune Response and the Clinical Allergic Reaction to Papain-like Cysteine Proteases from Fig, Kiwifruit, Papaya, Pineapple and Mites in an Italian Population

“…Actually, out of 341, three patients (0.88%) claimed allergy reaction to fig, two of them reporting OAS to the fruit ingestion and the third one reported an itchy reaction following skin contact to pruning but none of them was IgE positive to Fic c Ficin. Indeed, the literature reports describe that cysteine proteases can evoke itch in the absence of any allergic reaction [71,72]. Therefore, at least in the investigated population of allergics, and on the basis of the in vitro tests here reported, the fig cysteine protease does not appear to be the culprit of the reported allergy reactions due to fig exposure.…”

Clinically uninvolved but not healthy—The skin of patients with atopic dermatitis is primed for itch and inflammation

“…30 Chronic exposure to the exogenous cysteine protease Ficin contained in fig plants may promote sensitization to fig aeroallergens. 31 Prolonged contact of the pre-sensitized AD skin with cysteine proteases can lead to the release of alarmins and in consequence may promote Th2-type response and sensitization. 32,33 The sensitization of cowhage-activated mechanosensitive polymodal C-fibres in non-lesional skin of AD might also explain wool intolerance phenomenon, 34,35 which is one of the minor criteria of AD.…”

Halal enzymatic cosmetic ingredients: the role of enzymes in ingredients selection

“…According to a recent study, ficin possesses antioxidant and whitening effects in skin cells and has the potential to be developed as a novel bio-cosmetic substance (Cho et al, 2019). According to a recent study conducted by Malewicz et al, (2022), it has been found that ficin may be effective in translating mechanistic studies on the brain processes of cysteine proteases' pruritic and nociceptive actions. Furthermore, another study by Baidamshina et al, (2020) has demonstrated the stability and beneficial effects of chitosan-immobilized Ficin, which suggests that its addition to materials used in wound dressing may enhance the effectiveness of antimicrobial treatment and promote wound healing by preventing biofouling…”