9615 Background: AIAA affect up to half of AI-treated women with early stage breast cancer, and can lead to treatment discontinuation in 20-30%. The etiology is thought to be related to estrogen deprivation although the mechanism is unknown. In premenopausal women, lower estrogen levels have been associated with increased pain. Impaired descending pain inhibitory pathways, which may be a risk factor for developing chronic pain, have also been associated with lower estrogen levels. We prospectively tested whether AI-induced estrogen deprivation alters pain sensitivity, thereby increasing the risk of developing AIAA. Methods: Fifty postmenopausal women with early stage breast cancer initiating AI therapy were enrolled to the study. Subjects underwent experimental pressure pain testing and conditioned pain modulation (CPM) assessment and completed symptom questionnaires prior to AI initiation and after 3 months. Positive CPM values (>0) signify impaired descending pain inhibition. Serum estradiol concentrations were determined using an ultrasensitive assay. T-tests, Fisher’s exact test, and linear regression models were used to assess associations among baseline (BL) experimental pain measures, patient-reported pain, and clinical factors. P values <0.05 were considered statistically significant. Results: All subjects had decreased serum estradiol concentrations with AI therapy. No statistically significant change in pressure pain threshold or CPM with AI therapy was detected. In addition, no association between change in patient-reported pain with AI therapy and change in pain threshold or CPM was identified. Patients demonstrated impaired CPM at baseline (mean 8.0, SD 14.9), and this impairment was greater in patients previously treated with chemotherapy 14.4 vs 2.0, p=0.006), with non-significant trends towards this being more pronounced in those with more severe pain. Conclusions: AI therapy did not impact pressure pain threshold or CPM, suggesting that AIAA is not likely due to pain amplification from estrogen depletion. Studies examining chemotherapy-induced changes in pain processing are needed to better understand how these alterations might contribute to the pain that these patients often develop.