The overall goal of this proposal is to evaluate the change in clinical and experimental pain in men with prostate cancer (PCa) undergoing androgen deprivation therapy (ADT) and compare them with men with PCa not receiving ADT (non-ADT). The use of ADT is associated with a significant decrease in quality of life (QOL).This decrease is evident in both physical and mental composites of SF-36 QOL questionnaire. One of the aspects of the physical composite is the perception of pain. Preliminary cross-sectional studies have shown that men undergoing ADT report more clinical pain when compared with men in the non-ADT group and with age-matched healthy controls. As this increased pain perception is seen even in those androgen-deprived men without any metastatic disease, these findings implicate profound hypogonadism as the main etiology for these symptoms. Male hypogonadism is an inflammatory state associated with an increase in pro-inflammatory cytokines like IL-6 and TNF-?, both of which have been associated with clinical and experimental pain. Androgen deprivation therapy is also associated with metabolic abnormalities such as insulin resistance and hyperglycemia. Hence, it is unclear whether the increased prevalence/severity of pain in men on ADT is due to direct effects of hypogonadism or secondary to these metabolic abnormalities. We propose a prospective study in which: 1) we will compare changes in clinical pain reports and psychophysical pain responses between men undergoing ADT vs. non-ADT over a 6-month time period, and 2) We will assess the associations of various metabolic and inflammatory markers with pain perception and pain threshold in men undergoing ADT. The proposed study, in addition to advancing our understanding of the mechanism of pain development in men on ADT, is likely to have a significant clinical impact on the overall health-management of patients on ADT. The results of this study will guide physicians to use ADT for appropriate indications and to screen these patients for incident pain during ADT. Since androgen replacement is contraindicated in men with PCa, this study will lay the groundwork for prospective trials assessing the role of novel anti-inflammatory agents, insulin- sensitizing agents or SARMS (selective androgen receptor modulators) in the prevention and treatment of pain during ADT.

Public Health Relevance

Preliminary cross-sectional studies have shown that men undergoing androgen deprivation therapy have increased pain perception. This prospective observational study will compare changes in clinical pain reports and psychophysical experimental pain responses in men undergoing androgen deprivation therapy. The information obtained from this study will guide clinicians to use androgen deprivation therapy judiciously based on solid indications and will also lead to future studies evaluating various modalities for the prevention and treatment of pain during androgen deprivation therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA171316-02
Application #
8639503
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
O'Mara, Ann M
Project Start
2013-04-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
2
Fiscal Year
2014
Total Cost
$191,059
Indirect Cost
$70,330
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115