Persistent postmastectomy pain (PPMP) is a major individual and public health problem. Increasingly, psychosocial factors such as anxiety and catastrophizing are being revealed as crucial contributors to individual differences in pain processing and outcomes. Furthermore, differences in patients’ responses to standardized quantitative sensory testing (QST) may aid in the discernment of who is at risk for acute and chronic pain after surgery. However, characterization of the variables that differentiate those with PPMP from those whose acute postoperative pain resolves is currently incomplete. The purpose of this study was to investigate important surgical, treatment-related, demographic, psychophysical, and psychosocial factors associated with PPMP by comparing PPMP cases with PPMP-free controls. Pain was assessed using the breast cancer pain questionnaire to determine the presence and extent of PPMP. Psychosocial and demographic information were gathered via phone interview, and women underwent a QST session. Consistent with most prior research, surgical and disease-related variables did not differ significantly between cases and controls. Furthermore, treatment with radiation, chemotherapy, or hormone therapy was also not more common among those with PPMP. In contrast, women with PPMP did show elevated levels of distress-related psychosocial factors such as anxiety, depression, catastrophizing, and somatization. Finally, QST in nonsurgical body areas revealed increased sensitivity to mechanical stimulation among PPMP cases, while thermal pain responses were not different between the groups. These findings suggest that an individual’s psychophysical and psychosocial profile may be more strongly related to PPMP than their surgical treatment.

Intervertebral disc degeneration (IDD) is a common and debilitating disorder that results in reduced flexibility of the spine, pain, and reduced mobility. Risk factors for IDD include age, genetic predisposition, injury, and other environmental factors such as smoking. Loss of proteoglycans (PGs) contributes to IDD with advancing age. Currently there is a lack of a model for rapid investigation of disc aging and evaluation of therapeutic interventions. Here we examined progression of disc aging in a murine model of a human progeroid syndrome caused by deficiency of the DNA repair endonuclease, ERCC1–XPF (Ercc1−/Δ mice). The ERCC1-deficient mice showed loss of disc height and degenerative structural changes in their vertebral bodies similar to those reported for old rodents. Compared to their wild-type littermates, Ercc1−/Δ mice also exhibit other age-related IDD characteristics, including premature loss of disc PG, reduced matrix PG synthesis, and enhanced apoptosis and cell senescence. Finally, the onset of age-associated disc pathologies was further accelerated in Ercc1−/Δ mice following chronic treatment with the chemotherapeutic agent mechlorethamine. These results demonstrate that Ercc1−/Δ mice represent an accurate and rapid model of disc aging and provide novel evidence that DNA damage negatively impacts PG synthesis.

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Te President of the United States Te Speaker of the House Te President of the Senate Dear Sirs:On behalf of the Commission on Evidence-Based Policymaking, and pursuant to Public Law 114-140, we are pleased to submit the following report detailing our fndings and recommendations. We believe that adoption of the recommendations contained in our report will prove transformational, improving both the privacy protections aforded to the American public and the availability of rigorous evidence to inform policymaking.Over the course of its work, the Commission heard from numerous expert witnesses and members of the public, received extensive written public comment, and felded a survey of Federal agencies. Tis fact-fnding phase was followed by several months of deliberations. Te recommendations contained in the report have been agreed to unanimously by the 15 Members of the Commission.Te Commission envisions a future in which rigorous evidence is created efciently, as a routine part of government operations, and used to construct efective public policy. Advances in technology and statistical methodology, coupled with a modern legal framework and a commitment to transparency, make it possible to do this while simultaneously providing stronger protections for the privacy and confdentiality of the people, businesses, and organizations from which the government collects information.We call on the Congress and the President to act to ensure that this vision becomes a reality.