A new clinically-relevant rat model of letrozole-induced chronic nociceptive disorders

Among postmenopausal women with estrogen receptor-positive breast cancer, more than 80% receive hormone therapy including aromatase inhibitors (AIs). Half of them develop chronic arthralgia - characterized by symmetric articular pain, carpal tunnel syndrome, morning stiffness, myalgia and a decrease in grip strength which is associated treatment discontinuation. Only few animal studies have linked AI to nociception, none arthralgia. Thus, we developed new AI-induced nociceptive disorder model mimicking clinical symptoms induced AIs, using subcutaneous letrozole pellets ovariectomized (OVX) rats. Following plasma dosage at the end experiment (day 73), only rats least 90 ng/ml were considered significantly exposed (OVX + high LTZ group), whereas treated animals less pooled OVX low group. Chronic set rapidly was maintained for 70 days Furthermore, saw no alteration locomotion, or experimental anxiety during this period. Bone parameters femora altered all compared Sham+vehicle pellet. A mechanistic analysis focused on TRPA1, receptor suspected mediate AI-evoked showed modification its expression DRG. This long-lasting rat model, efficiently reproduces affecting patients' daily activities quality-of-life. It should help study pathophysiology promote development therapeutic strategies.