Shannon M. Smith’s research while affiliated with University of Rochester Medical Center and other places

Chronic pelvic pain (CPP) in women is characterized by complex etiologies, psychosocial comorbidities, and treatment difficulties. Dysmenorrhea and the associated psychosocial and functional impairment beginning in adolescence may facilitate the transition into more debilitating CPP. This study describes dysmenorrhea history in a clinical sample of women with CPP and identifies predictors of dysmenorrhea catastrophizing (anxiously ruminating about dysmenorrhea symptoms) and functional impairment. From January-August 2020, we recruited 105 female patients (18+ years of age) with CPP receiving care through a tertiary center for chronic pelvic/vulvar pain. Patients completed a questionnaire that elicited dysmenorrhea information prior to the onset of their non-cyclical CPP. Questions included past dysmenorrhea symptoms and treatments, dysmenorrhea catastrophizing, and dysmenorrhea interference with activities of daily living. Multiple linear regression models identified predictors of dysmenorrhea catastrophizing and interference. On average, participants were 36 years of age and predominantly non-Hispanic white (82%). The majority (78%) experienced dysmenorrhea with each or most menstrual cycles, rated as moderate or greater intensity, within 5 years of menarche. Of these, 55% previously sought treatment. Over-the-counter pain medications, heating pad, and birth control pills/patch/ring were the most commonly reported dysmenorrhea treatments, and 10% of patients reported history of prescription opioids and 11% of marijuana use. Duration of dysmenorrhea within each menstrual period and dysmenorrhea intensity were most predictive of dysmenorrhea catastrophizing. Dysmenorrhea intensity and catastrophizing were predictive of dysmenorrhea interference, with catastrophizing mediating 62% (95% CI = 42%-83%) of the effect of dysmenorrhea intensity on interference. The majority of women in our sample reported dysmenorrhea prior to developing CPP, with some using opioids and marijuana for managing dysmenorrhea. The duration and intensity of dysmenorrhea were key predictors of dysmenorrhea catastrophizing, which in turn largely explained dysmenorrhea-associated functional impairment. These findings underscore the importance of early intervention for dysmenorrhea.

Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (e.g., opioid use disorder) and adverse outcomes (e.g., respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents IMMPACT consensus recommendations for the design of opioid sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.

Clinical outcome assessments (COAs) measure outcomes that are meaningful to patients in clinical trials and are critical for determining whether a treatment is effective. The objectives of this study are to (1) describe the different types of COAs and provide an overview of key considerations for evaluating COAs, (2) review COAs and other outcome measures for chronic pain treatments that are recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) or other expert groups, and (3) review advances in understanding pain-related COAs that are relevant to clinical trials. The authors reviewed relevant articles, chapters, and guidance documents from the European Medicines Agency and U.S. Food and Drug Administration. Since the original core set of outcome measures were recommended by IMMPACT 14 years ago, several new advancements and publications relevant to the measurement or interpretation of COAs for chronic pain trials have emerged, presenting new research opportunities. Despite progress in the quality of measurement of several outcome domains for clinical trials of chronic pain, there remain some measurement challenges that require further methodological investigation.

There is tremendous interpatient variability in the response to analgesic therapy (even for efficacious treatments), which can be the source of great frustration in clinical practice. This has led to calls for “precision medicine” or personalized pain therapeutics (ie, empirically based algorithms that determine the optimal treatments, or treatment combinations, for individual patients) that would presumably improve both the clinical care of patients with pain and the success rates for putative analgesic drugs in phase 2 and 3 clinical trials. However, before implementing this approach, the characteristics of individual patients or subgroups of patients that increase or decrease the response to a specific treatment need to be identified. The challenge is to identify the measurable phenotypic characteristics of patients that are most predictive of individual variation in analgesic treatment outcomes, and the measurement tools that are best suited to evaluate these characteristics. In this article, we present evidence on the most promising of these phenotypic characteristics for use in future research, including psychosocial factors, symptom characteristics, sleep patterns, responses to noxious stimulation, endogenous pain-modulatory processes, and response to pharmacologic challenge. We provide evidence-based recommendations for core phenotyping domains and recommend measures of each domain.

Objective: Identifying biomarkers is a priority in translational chronic pain research. Dehydroepiandrosterone (DHEA) and its sulfated form, DHEA-S, are adrenocortical steroids in the blood with neuroprotective properties that also produce sex hormones. They may capture key sex-specific neuroendocrine mechanisms of chronic pain. Design: Cross-sectional study. Methods: Using data from 1,216 community-dwelling adults aged 34–84 from the Midlife in the United States (MIDUS) cohort, we examined blood DHEA and DHEA-S levels in association with chronic pain in men and women, adjusting for demographics, chronic diseases, medications including opioids, and psychosocial factors. If an association was found, we further explored dose-response relationships by the number of pain locations and the degree of pain interference. Results: In women, chronic pain was associated with 0.072 lower (95% confidence interval [CI], –0.127 to –0.017) log10 DHEA-S µg/dL, with pain in one to two locations associated with 0.068 lower (95% CI, –0.131 to –0.006) and in three or more locations 0.071 lower (95% CI, –0.148 to 0.007) log10 DHEA-S (P for trend = 0.074). Furthermore for women, low-interference pain was associated with 0.062 lower (95% CI, –0.125 to –0.000), whereas high-interference pain was associated with 0.138 lower (95% CI, –0.233 to –0.043) log10 DHEA-S (P for trend = 0.004). Chronic pain was not associated with DHEA or DHEA-S levels in men or DHEA levels in women. Conclusions: Chronic pain and its functional interference correspond to lower blood DHEA-S levels in women.

Interpreting randomized clinical trials (RCTs) is crucial to making decisions regarding the use of analgesic treatments in clinical practice. In this article, we report on an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), the purpose of which was to recommend approaches that facilitate interpretation of analgesic RCTs. We review issues to consider when drawing conclusions from RCTs, as well as common methods for reporting RCT results and the limitations of each method. These issues include the type of trial, study design, statistical analysis methods, magnitude of the estimated beneficial and harmful effects and associated precision, availability of alternative treatments and their benefit-risk profile, clinical importance of the change from baseline both within and between groups, presentation of the outcome data, and the limitations of the approaches used.

OBJECTIVE To synthesize the epidemiological findings for the associations between dysmenorrhea, including primary dysmenorrhea and endometriosis-associated dysmenorrhea, and any chronic pain conditions, including chronic pelvic pain, and chronic non-pelvic pain. DATA SOURCES PubMed, Embase, and CINAHL from inception to December 2019. STUDY ELIGIBILITY CRITERIA Observational population-based studies in which the relationship between dysmenorrhea and the presence or severity of chronic pain was examined. STUDY APPRAISAL AND SYNTHESIS METHODS Each study was double-coded and evaluated for bias based on the modified Newcastle and Ottawa Scale. Random-effect meta-analyses were conducted to quantify the associations between dysmenorrhea and the presence of chronic pelvic and non-pelvic pain. RESULTS Out of 9,452 records, 32 studies were included, with 14 reporting associations between dysmenorrhea and chronic pelvic pain, and 20 for dysmenorrhea and chronic non-pelvic pain. Primary dysmenorrhea and endometriosis-associated dysmenorrhea were examined in 7 studies, respectively. Over 30% of the studies were categorized as poor quality, 56% as moderate, and 12.5% as high. Dysmenorrhea was positively associated with both the presence and severity of chronic pelvic and non-pelvic pain conditions. Based on 6,689 women from 8 studies, those with chronic pelvic pain had 2.43 (95% confidence interval = 1.98, 2.99, I² = 42%) times the odds of having dysmenorrhea compared to those without. Based on 3,750 women from 11 studies, those with chronic non-pelvic pain had 2.62 (95% confidence interval = 1.84, 3.72, I² = 72%) times the odds of having dysmenorrhea compared to those without. Overall, dysmenorrhea was associated with 2.50 (95% confidence interval = 2.02, 3.10) times the odds of chronic pain, which did not differ by chronic pelvic vs chronic non-pelvic pain, community vs clinical populations, or different geographical regions. CONCLUSIONS Dysmenorrhea may be a general risk factor for chronic pain, although whether primary dysmenorrhea increases the risk for chronic pain is unclear. Given that adolescence is a sensitive period for neurodevelopment, elucidating the role of primary dysmenorrhea in pain chronicity in future longitudinal studies is important for preventing both chronic pelvic and non-pelvic pain.

Objective: Current treatments for chronic pain have limited effectiveness and tolerability. With growing interest in the potential of cannabinoids, there is a need to inform risk-benefit considerations. Thus, this focused systematic review assesses the quality of safety assessment and reporting in chronic noncancer pain cannabinoid trials. Methods: The protocol for this review has been published, and, registered in PROSPERO. We searched MEDLINE, EMBASE, The Cochrane Library, Scopus and PsychINFO for double-blind, placebo-controlled, randomized controlled trials of cannabinoids for chronic pain, with a primary outcome related to pain. The primary review outcome is adherence to the 2004 CONSORT Harms extension. Secondary outcomes included type, reporting method, frequency and severity of AEs, trial participant withdrawals, and reasons for withdrawals. Results: In total, 43 studies (4,436 participants) were included. Type of cannabinoid (number of studies) included nabiximols (12), dronabinol (8), nabilone (7), oral cannabis extract preparations (5), smoked THC (5), vaporised THC (3), novel synthetic cannabinoids (2), sublingual cannabis extract preparations (1). The median CONSORT score was 7. On average, 3-4 recommendations of the CONSORT guidelines were not being met in trials. Seventeen trials did not provide their method of adverse event (AE) assessment, fourteen trials did not report on serious adverse events (SAEs) and, seven trials provided no quantitative data about AEs. Discussion: Better harms assessment and reporting are needed in chronic pain cannabinoid trials. Improvements may be achieved through: expanded education/knowledge translation, increased research regulation by ethics boards, funding agencies and journals, and greater emphasis on safety assessment and reporting throughout research training.

Introduction: The subjective experience of drug craving is a prominent and common clinical phenomenon for many individuals diagnosed with opioid use disorder (OUD), and could be a valuable clinical endpoint in medication development studies. The purpose of this scoping review is to provide an overview and critical analysis of opioid craving assessments located in the published literature examining OUD. Method: Studies were identified through a search of PubMed, Embase, and PsychInfo databases and included for review if opioid craving was the focus and participants were diagnosed with or in treatment for OUD. Results: Fifteen opioid craving assessment instruments were identified across the 87 studies included for review. The most common were the Visual Analog Scale (VAS, 41 studies), Desires for Drug Questionnaire (DDQ, 12 studies), Heroin Craving Questionnaire (HCQ, 10 studies), and Obsessive-Compulsive Drug Use Scale (OCDUS, 10 studies). Craving assessments varied considerably in their format, content, time frame, and underlying subscales, and only 6 of 15 had been psychometrically evaluated. Discussion: This review identified a variety of opioid craving assessments, but few had been evaluated for their psychometric properties making it difficult to ascertain whether craving is being assessed optimally in studies of OUD. Thus, the development of a reliable and valid opioid craving assessment would be worthwhile and could be guided by recently published Food and Drug Administration Clinical Outcome Assessment (COA) guidelines. Importantly, a COA focused on opioid craving could be a valuable addition to research studies designed to evaluate novel treatments for OUD.