Predicting chronic postsurgical pain: current evidence and a novel program to develop predictive biomarker signatures.

ABSTRACT: Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.

Health care utilization differences between First Nations people and the general population with inflammatory bowel disease: a retrospective cohort study from Saskatchewan, Canada.

BACKGROUND: Indigenous people in Canada often face barriers to access specialized care, with limited data in evaluating health care utilization among Indigenous people with inflammatory bowel disease (IBD). We aimed to compare health care utilization between First Nations patients and those in the general population diagnosed with IBD in Saskatchewan. METHODS: We conducted a patient-oriented, population-based, retrospective cohort study by linking administrative health databases of Saskatchewan between fiscal years 1998/99 and 2017/18. We designed and completed this study in partnership with Indigenous patients and family advocates. We applied a validated algorithm to identify IBD incident cases and then used the self-declared First Nations status variable to divide those cases. We applied a 1:5 ratio for age and sex matching and used Cox proportional models to assess associations. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. RESULTS: We created a matched cohort with 696 IBD incident cases: 116 First Nations patients and 580 patients in the general population. We observed differences between the groups for IBD-specific hospital admissions (HR 1.33, 95% CI 1.01-1.75), IBD-related hospital admissions (HR 1.55, 95% CI 1.20-2.01), medication claims for IBD (HR 0.52, 95% CI 0.41-0.65) and 5-aminosalicylic acid claims (HR 0.56, 95% CI 0.45-0.71) adjusting by rural or urban residence and diagnosis type. There were no significant differences in the hazard rate of outpatient gastroenterology visits (HR 1.13, 95% CI 0.90-1.41), colonoscopies (HR 1.14, 95% CI 0.92-1.41) and surgeries for IBD (HR 1.14, 95% CI 0.80-1.64). INTERPRETATION: We identified that First Nations patients diagnosed with IBD had a higher rate of hospital admissions owing to IBD than patients in the general population diagnosed with IBD. We also found an inverse association between First Nations status and having prescription medication claims for IBD.

Opioid pharmacotherapy for chronic non-cancer pain in the United States: a research guideline for developing an evidence-base.

UNLABELLED: This document reports the consensus of an interdisciplinary panel of research and clinical experts charged with reviewing the use of opioids for chronic noncancer pain (CNCP) and formulating guidelines for future research. Prescribing opioids for chronic noncancer pain has recently escalated in the United States. Contrasting with increasing opioid use are: 1) The lack of evidence supporting long-term effectiveness; 2) Escalating misuse of prescription opioids including abuse and diversion; and 3) Uncertainty about the incidence and clinical salience of multiple, poorly characterized adverse drug events (ADEs) including endocrine dysfunction, immunosuppression and infectious disease, opioid-induced hyperalgesia and xerostomia, overdose, falls and fractures, and psychosocial complications. Chief among the limitations of current evidence are: 1) Sparse evidence on long-term opioid effectiveness in chronic pain patients due to the short-term time frame of clinical trials; 2) Insufficiently comprehensive outcome assessment; and 3) Incomplete identification and quantification of ADEs. The panel called for a strategic interdisciplinary approach to the problem domain in which basic scientists and clinicians cooperate to resolve urgent issues and generate a comprehensive evidence base. It offered 4 recommendations in 3 areas: 1) A research strategy for studying the effectiveness of long-term opioid pharmacotherapy; 2) Improvements in evidence-generation methodology; and 3) Potential research topics for generating new evidence. PERSPECTIVE: Prescribing opioids for CNCP has outpaced the growth of scientific evidence bearing on the benefits and harms of these interventions. The need for a strong evidence base is urgent. This guideline offers a strategic approach to creating a comprehensive evidence base to guide safe and effective management of CNCP.

Effects of dopamine and estrogen upon cortical neurons that express parvalbumin in vitro.

The purpose of these experiments was to study the effects of dopamine (DA) and 17 beta-estradiol (EST) upon parvalbumin expression in rodent frontal cortex during development. Organotypic slice cultures of the frontal cortex were prepared from neonatal rats (postnatal day 2/3) and maintained for 14 days in vitro in serum-enriched medium and medium treated with either DA, EST or DA+EST. Cultured slices were then fixed and immunostained for parvalbumin immunoreactivity. Under control conditions, parvalbumin immunoreactive somata and fibers were primarily found in the deep laminae. In comparison, slices in all treatment groups exhibited a pattern of parvalbumin expression that was significantly different than controls. Specifically, DA treatment increased the percentage of parvalbumin immunoreactive somata, dendritic length and density in the deep cortical layers, but not in the superficial cortical layers. Both EST and DA+EST treatments induced similar changes in both the deep and the superficial cortical layers. These treatment induced changes represent more mature patterns of parvalbumin expression when compared to controls, indicating that both DA and EST enhance cortical expression of the protein.