Mechanisms of Aromatase Inhibitor-induced Musculoskeletal Symptoms.

摘要

The use of aromatase inhibitor (AI) therapies in breast cancer is limited in many patients because they induce musculoskeletal pain; however, the effects of pharmacologic inhibition of estrogen synthesis on nociceptive changes in animal models of pain are unknown. To address this issue, we determined whether administration of the AI letrozole to male rats would alter nociceptive responses to mechanical or thermal stimuli. Daily dosing of 5 mg/kg letrozole in male rats induced mechanical, but not thermal hypernociception. Additionally, we have demonstrated that treatment with the aromatase inhibitors letrozole and exemstane enhances nociceptive response to ATP, suggesting sensitization to ATP may play a role in AI-induced pain. We further demonstrate that aromatase expression in rat dorsal root ganglia is maintained when these cells are cultured. In DRG cultures, letrozole treatment enhances ATP-mediated sensitization, as measured by enhanced capsaicin-evoked release of iCGRP. Further studies are needed to determine whether AIs directly alter sensory neuron function in vivo.