Effect of estrogen depletion on pain sensitivity in aromatase inhibitor-treated women with early-stage breast cancer

N Lynn Henry, Anna Conlon, Kelley M Kidwell, Kent Griffith, Jeffrey B Smerage, Anne F Schott, Daniel F Hayes, David A Williams, Daniel J Clauw, Steven E Harte, N Lynn Henry, Anna Conlon, Kelley M Kidwell, Kent Griffith, Jeffrey B Smerage, Anne F Schott, Daniel F Hayes, David A Williams, Daniel J Clauw, Steven E Harte

Abstract

Aromatase inhibitors (AIs), which are used to treat breast cancer, inhibit estrogen production in postmenopausal women. AI-associated musculoskeletal symptoms occur in approximately half of treated women and lead to treatment discontinuation in 20 to 30%. The etiology may be due in part to estrogen deprivation. In premenopausal women, lower estrogen levels have been associated with increased pain as well as with impairment of descending pain inhibitory pathways, which may be a risk factor for developing chronic pain. We prospectively tested whether AI-induced estrogen deprivation alters pain sensitivity, thereby increasing the risk of developing AI-associated musculoskeletal symptoms. Fifty postmenopausal breast cancer patients underwent pressure pain testing and conditioned pain modulation (CPM) assessment prior to AI initiation and after 3 and 6 months. At baseline, 26 of 40 (65%) assessed patients demonstrated impaired CPM, which was greater in those who had previously received chemotherapy (P = .006). No statistically significant change in pressure pain threshold or CPM was identified following estrogen deprivation. In addition, there was no association with either measure of pain sensitivity and change in patient-reported pain with AI therapy. AI-associated musculoskeletal symptoms are not likely due to decreased pain threshold or impaired CPM prior to treatment initiation, or to effects of estrogen depletion on pain sensitivity.

Perspective: This article presents our findings of the effect of estrogen deprivation on objective measures of pain sensitivity. In postmenopausal women, medication-induced estrogen depletion did not result in an identifiable change in pressure pain threshold or CPM. Impaired CPM may be associated with chemotherapy.

Keywords: Pain threshold; aromatase inhibitor; breast cancer; conditioned pain modulation; estrogen deprivation.

Conflict of interest statement

Potential conflicts of interest: NLH receives research funding from AstraZeneca, Lilly Pharmaceuticals, and sanofi aventis. DFH received research funding from AstraZeneca, Novartis, Pfizer, and Veridex LLC. DJC has received consulting income and grant support from Pfizer, Forest, Wyeth, Cerephex and Nuvo, and consulting income from Lilly, UCB, Cerephex, Tonix, and Purdue Labs. SEH has received grant support from Cerephex, Merck and Forest Laboratories. No other authors reported conflicts of interest.

Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Patient flow diagram.
Figure 2. Effect of estrogen depletion on…
Figure 2. Effect of estrogen depletion on quantitative sensory testing measures
Change in (A) patient-reported pain, (B) pressure pain threshold (Pain50) and (B) conditioned pain modulation (CPM) with aromatase inhibitor therapy. Individual patients are represented by circles at baseline (BL), squares at 3 months (mo), and triangles at 6 months. Points above the horizontal dotted line in C reflect impaired CPM.
Figure 3. Mean conditioned pain modulation (CPM)…
Figure 3. Mean conditioned pain modulation (CPM) for those who were or were not treated with chemotherapy (chemo)
Circles represent individual patients who received chemotherapy, squares represent individual patients who did not receive chemotherapy, and horizontal lines represent mean values.

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