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Advances in dermatology and venereology Acta Dermato-Venereologica
Effects of Film Dressings on Itch Hypersensitivity Using Murine Dry Skin Models
Tomoyuki IWANAGA 1 , 2 # , Mitsutoshi TOMINAGA 1 # , Yui HIRATA 2 , Hironori MATSUDA 1 , Tomomasa SHIMANUKI 2 , Hideoki OGAWA 1 , 3 and Kenji TAKAMORI 1 , 4 *
1
Institute for Environmental and Gender Specific Medicine , Juntendo University Graduate School of Medicine , 2-1-1 Tomioka , Urayasu , Chiba 279-0021 , 2 R & D laboratories , Pola Pharma Inc ., 560 Kashio-cho , Totsuka-ku , Yokohama , Kanagawa , 3 Atopy ( Allergy ) Research Center , Juntendo University Graduate School of Medicine , Tokyo 113-8421 , and 4 Department of Dermatology , Juntendo University Urayasu Hospital , Chiba , Japan . * E-mail : ktakamor @ juntendo . ac . jp
#
These authors contributed equally to this work . Accepted Jun 26 , 2018 ; Epub ahead of print Jun 29 , 2018
Atopic dermatitis ( AD ) is characterized by chronic cutaneous inflammation and dryness with skin barrier dysfunction . Chronic and intractable itch in patients with AD markedly diminishes their quality of life ( 1 , 2 ). Low-threshold mechanical stimuli , such as wool fibres , are irritants to the skin of patients with AD ( 3 ). This phenomenon is known as alloknesis ( touch-evoked itch ) ( 4 ), and the hypersensitivity results in an itch-scratch cycle , which causes refractory AD ( 5 ). The number of epidermal nerve fibres in patients with AD is higher than in healthy individuals , and a reduction in intraepidermal nerve fibres by psoralen and ultraviolet A ( PUVA ) therapy improves both pruritus and dermatitis scores in patients with AD ( 6 ). Topical treatment of the nerve repulsion factor semaphorin 3A significantly reduced intraepidermal nerve density , which suppressed scratching behaviour and improved dermatitis scores in AD model NC / Nga mice induced by Dermatophagoides farina body ointment ( 7 ). Therefore , intraepidermal nerve fibres are a likely pathogenic factor for itch hypersensitivity , including alloknesis in AD ( 8 ), but conventional treatments for alloknesis are limited . Therefore , it is necessary to develop preventative and therapeutic approaches for alloknesis in AD .
Film dressings are transparent sheets coated with an adhesive , and some are thin enough ( several 10 µ m ) to be almost invisible on the skin and do not interfere with tactile transmission . They are used for wound treatment to provide an appropriately moist environment and act as a barrier to contamination . However , it is unclear whether film dressings prevent epidermal hyper-innervation or alloknesis in dry skin-based diseases , such as AD . This study evaluated 2 different thicknesses of film dressings ; Tegaderm™ ( TDM , 24 µ m ; 3M Japan , Tokyo , Japan ) and Perme Roll™ Lite ( PMR , 8 µ m ; Nitto , Tokyo , Japan ), using 2 murine dry skin models for evaluation of epidermal hyper-innervation or alloknesis efficacies .
MATERIALS AND METHODS
All animals were housed in the experimental animal facility of Juntendo University Graduate School of Medicine , and all animal procedures were approved by the Animal Care and Use Committee of Juntendo University Graduate School of Medicine . The study conformed to the National Institute for Health guidelines for animal research .
The protocol for induction of epidermal hyper-innervation of male ICR mice ( 10 weeks old ; SLC Japan , Shizuoka , Japan ) by cutaneous barrier disruption has been described previously ( 9 ). A 20-mm square of TDM , PMR , or nothing ( positive control ) was applied to an acetone-treated area immediately after 5 min of acetone treatment , and distilled water-treated mice were used as a negative control ( n = 6 per group ). Skin samples were taken after an additional 48 h , and the nerve fibres in 20- µ m cryosections were stained immunohistochemically using rabbit anti-protein gene product 9.5 ( PGP9.5 , 1:400 dilution ; Enzo Life Sciences Inc ., NY , USA ).
The protocol for the alloknesis assay by cutaneous barrier disruption has been described previously ( 4 ). Briefly , a cotton soaked with a mixture of acetone and diethylether ( 1:1 ) was applied to the rostral section of the shaved back of C57BL / 6NCrSlc mice ( 10 weeks old ; SLC Japan , Shizuoka , Japan ) for 15 s , followed immediately by applying distilled water for 30 s ( AEW treatment ), and the negative control group was treated only with distilled water for 45 s , twice daily for 8 days . On the day after the last AEW treatment , 5 separate innocuous mechanical stimuli were applied using a von Frey filament ( 0.7 mN ; DanMic Global , CA , USA ) to the AEW- or water-treated site to determine the sections suitable for alloknesis assessment ( AEW ; n = 12 , water ; n = 4 ). Next , we applied TDM , PMR , or nothing ( positive control ) with a diameter of 8 mm on the right or left rostral section ( alloknesis spot ) of the AEW-treated site on the day after 8 days of AEW treatment ( n = 8 per group ). The evaluation sites of each group were assigned equally on the left and right ( Table SI 1 ). An alloknesis score with a maximum score of 10 was evaluated immediately after application of the film dressings .
RESULTS
Epidermal hyper-innervation model . The numbers of PGP9.5-immunoreactive nerve fibres in and penetrating into the epidermis were significantly increased in the acetone-treated group ( Fig . 1a , b , e , f ). Both the number of nerve fibres in , and penetrating into , the epidermis were significantly decreased by TDM or PMR treatment ( Fig . 1c – f ).
Alloknesis model . The AEW- or water-treated site was divided into 9 sections ( Fig . S1a 1 ). Alloknesis scores on the right or left rostral section of the AEW-treated site were significantly higher than those on the same sections of the water-treated site and on the other 7 sections of the AEWtreated site ( Fig . S1b 1 ). TDM or PMR with a diameter of 8 mm was applied on the alloknesis spot of the AEW-treated site on the day after 8 days of AEW treatment ( Fig . S1c 1 ). TDM and PMR application significantly prevented induction of alloknesis on the right or left rostral section of the AEW-treated site Fig . S1d 1 ).
1 https :// www . medicaljournals . se / acta / content / abstract / 10.2340 / 00015555-2998 doi : 10.2340 / 00015555-2998 Acta Derm Venereol 2018 ; 98 : 902 – 903
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2018 Acta Dermato-Venereologica .