Topical transient receptor potential ankyrin 1 antagonist treatment attenuates nociception and inflammation in an ultraviolet B radiation-induced burn model in mice

• Published in: Journal of dermatological science Vol. 97; no. 2; pp. 135 - 142
• Main Authors: Fialho, Maria Fernanda Pessano, Brum, Evelyne da Silva, Pegoraro, Natháli Schopf, Couto, Ana Claudia Gontijo, Trevisan, Gabriela, Cruz, Letícia, Oliveira, Sara Marchesan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2020
• Subjects: Antinociception; Calcium influx; HC030031; Hydrogen peroxide; Sunburn; UVB; UVB; UV; Hydrogen peroxide; TRPA1; DMSO; HRPO; Antinociception; H2O2; PWT; MPO; Calcium influx; Sf; Sunburn; ANOVA; ROS; Imax; KRB; SEM; SP; HC030031
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2020.01.005

•Peripheral participation of TRPA1 channel in UVB radiation-induced sunburn.•HC030031, a TRPA1 antagonist, reduces UVB radiation-induced nociception.•HC030031 reduces inflammatory parameters in a UVB radiation-induced sunburn model. Ultraviolet B (UVB) radiation exposure promotes sunburn and thereby acute and chronic inflammatory processes, contributing to pain development and maintenance. New therapeutic alternatives are necessary because typical treatments can cause adverse effects. An attractive alternative would be to target the transient receptor potential ankyrin 1 (TRPA1), a calcium-permeable, non-selective cation channel, which is involved in a variety of inflammatory pain models. Evaluate the peripheral participation of TRPA1 using a topical treatment (HC030031 gel formulation; a selective TRPA1 antagonist) in nociception and inflammation caused by a UVB radiation-induced burn model in male mice (25–30 g). The mice were anaesthetised, and just the right hind paw was exposed to UVB radiation (0.75 J/cm2). Topical treatments were applied immediately after irradiation and once a day for 8 days. HC030031 gel presented suitable pH and spreadability factor, ensuring its quality and the therapeutic effect. HC030031 0.05 % reversed UVB-induced mechanical and cold allodynia, with maximum inhibition (Imax) of 69 ± 13 % and 100 % (on day 4), respectively. HC030031 0.05 % also reduced the paw edema and MPO activity, with Imax of 77 ± 6 % (on day 5) and 69 ± 28 %, respectively. Likewise, UVB radiation increased the H2O2 levels (a TRPA1 agonist) and the Ca2+ influx in mice spinal cord synaptosomes. UVB radiation-induced Ca2+ influx was reduced by HC030031. These findings confirm the activation of the TRPA1 channel by UVB radiation, suggesting that topical TRPA1 antagonists can be a new strategy for the adjuvant treatment of sunburn-associated pain and inflammation.