Calca, which encodes the neuropeptide calcitonin gene-related peptide (CGRP), is involved in multiple biological functions. It is expressed in certain subpopulations of neurons, and these neurons participate in relaying aversive sensory information, taste processing, and are likely involved in homeostatic functions [4,6].

In KO mouse models, CALCA-/-mice show increased cartilage degeneration and subchondral bone loss with elevated osteoclast numbers in a post-traumatic osteoarthritis (ptOA) model, suggesting that Calca-encoded peptides may play a role in ptOA progression [5]. In addition, preventing parabrachial Calca neurons from releasing neurotransmitters demonstrated that their activation is necessary for the manifestation and maintenance of chronic pain, and directly stimulating these neurons can drive nociplasticity [1,2]. Chemogenetic inhibition of Calca neurons during second-order conditioning (SOC) pairing attenuated SOC, indicating their role in forming second-order memories [3].

In conclusion, Calca is crucial for functions related to pain, nociplasticity, taste, and osteoarthritis. Mouse models, especially KO models, have been instrumental in revealing these functions, providing insights into potential therapeutic targets for chronic pain and osteoarthritis.