Calca, encoding the neuropeptide calcitonin gene-related peptide (CGRP), is involved in multiple biological functions. It plays a role in relaying aversive sensory information and is associated with functions such as pain perception, learning and memory, and taste processing. The gene is expressed in certain neurons of the parabrachial nucleus (PBN), and its associated pathways are crucial for maintaining homeostasis and neural plasticity [1-4, 9]. Genetic models, like KO/CKO mouse models, are valuable tools for studying Calca's functions.

In KO mouse models, CALCA-/-mice show increased cartilage degeneration, subchondral bone loss, and elevated osteoclast numbers in a post-traumatic osteoarthritis (ptOA) model compared to αCGRP-/-and WT mice, indicating that CALCA-encoded peptides may be novel targets for ptOA treatment [4]. Preventing PBN Calca neurons from releasing neurotransmitters demonstrated that activation of these neurons is necessary for chronic pain manifestation and maintenance, and direct stimulation shows they are sufficient to drive nociplasticity [1,2]. Chemogenetic inhibition of Calca neurons during CS1-CS2 pairing attenuated second-order conditioning, suggesting their role in associative learning [3].

In conclusion, Calca is essential for functions related to pain, learning, and taste. Studies using KO/CKO mouse models have revealed its significance in diseases like ptOA and nociplastic pain. These models contribute to understanding the role of Calca in specific biological processes and offer potential therapeutic targets for related diseases.