TRPA1, the transient receptor potential ankyrin 1, is a non-selective cation channel permeable to Ca(2+), Na(+), and K(+). It is expressed in pain-sensing neurons, other tissues, and cells of the immune system [2,3,5]. It functions as a promiscuous chemical nocisensor involved in noxious cold, heat, and mechanical sensation, and is also associated with multiple physiological functions like maintaining cell membrane potential and regulating signal transduction [3,7]. It participates in pathways related to pain, inflammation, and potentially in the development of diseases such as pulmonary fibrosis [1,4,7]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

Pre-clinical evidence from murine models of pain diseases shows that numerous mechanisms converge on the oxidative stress-Schwann cell TRPA1 pathway to sustain chronic pain, suggesting TRPA1 as a potential target for pain relief [1]. TRPA1 in immune cells has been linked to various inflammatory conditions like arthritis, anaphylaxis, and inflammatory bowel disease, indicating its role in exacerbating or mediating defensive responses in these diseases [5]. In the context of obesity, TRPA1 agonism has been associated with body weight reduction, hormone secretion, and thermogenesis [6].

In conclusion, TRPA1 is a crucial channel involved in multiple biological functions. Mouse models, especially KO/CKO models, have revealed its significance in pain, inflammation, obesity-related processes, and potentially pulmonary fibrosis. Understanding TRPA1 through these models offers insights into disease mechanisms and potential therapeutic strategies for these disease areas.

References:

1. Souza Monteiro de Araujo, Daniel, Nassini, Romina, Geppetti, Pierangelo, De Logu, Francesco. 2020. TRPA1 as a therapeutic target for nociceptive pain. In Expert opinion on therapeutic targets, 24, 997-1008. doi:10.1080/14728222.2020.1815191. https://pubmed.ncbi.nlm.nih.gov/32838583/

2. Meents, Jannis E, Ciotu, Cosmin I, Fischer, Michael J M. 2018. TRPA1: a molecular view. In Journal of neurophysiology, 121, 427-443. doi:10.1152/jn.00524.2018. https://pubmed.ncbi.nlm.nih.gov/30485151/

3. Zygmunt, Peter M, Högestätt, Edward D. . TRPA1. In Handbook of experimental pharmacology, 222, 583-630. doi:10.1007/978-3-642-54215-2_23. https://pubmed.ncbi.nlm.nih.gov/24756722/

4. Li, Chao, Xu, Jiawen, Abdurehim, Aliya, Xie, Junbo, Zhang, Yanqing. 2023. TRPA1: A promising target for pulmonary fibrosis? In European journal of pharmacology, 959, 176088. doi:10.1016/j.ejphar.2023.176088. https://pubmed.ncbi.nlm.nih.gov/37777106/

5. Naert, Robbe, López-Requena, Alejandro, Talavera, Karel. 2021. TRPA1 Expression and Pathophysiology in Immune Cells. In International journal of molecular sciences, 22, . doi:10.3390/ijms222111460. https://pubmed.ncbi.nlm.nih.gov/34768891/

6. Mahajan, Neha, Khare, Pragyanshu, Kondepudi, Kanthi Kiran, Bishnoi, Mahendra. 2021. TRPA1: Pharmacology, natural activators and role in obesity prevention. In European journal of pharmacology, 912, 174553. doi:10.1016/j.ejphar.2021.174553. https://pubmed.ncbi.nlm.nih.gov/34627805/

7. Yao, Kaifang, Dou, Baomin, Zhang, Yue, Wang, Shenjun, Guo, Yi. 2023. Inflammation-the role of TRPA1 channel. In Frontiers in physiology, 14, 1093925. doi:10.3389/fphys.2023.1093925. https://pubmed.ncbi.nlm.nih.gov/36875034/