Dissecting Genetic Mechanisms of Differential Locomotion, Depression, and Allodynia after Spinal Cord Injury in Three Mouse Strains.

Strain differences have been reported for motor behaviors, and only a subset of spinal cord injury (SCI) patients develop neuropathic pain, implicating genetic or genomic contribution to this condition. Here, we evaluated neuropsychiatric behaviors in A/J, BALB/c, and C57BL/6 male mice and tested genetic or genomic alterations following SCI. A/J and BALB/c naive mice showed significantly less locomotor activity and greater anxiety-like behavior than C57BL/6 mice. Although SCI elicited locomotor dysfunction, C57BL/6 and A/J mice showed the best and the worst post-traumatic recovery, respectively. Mild (m)-SCI mice showed deficits in gait dynamics. All moderate/severe SCI mice exhibited similar degrees of anxiety/depression. mSCI in BALB/c and A/J mice resulted in depression, whereas C57BL/6 mice did not exhibit depression. mSCI mice had significantly lower mechanical thresholds than their controls, indicating high cutaneous hypersensitivity. C57BL/6, but not A/J and BLAB/c mice, showed significantly lower heat thresholds than their controls. C57BL/6 mice exhibited spontaneous pain. RNAseq showed that genes in immune responses and wound healing were upregulated, although A/J mice showed the largest increase. The cell cycle and the truncated isoform of trkB genes were robustly elevated in SCI mice. Thus, different genomics are associated with post-traumatic recovery, underscoring the likely importance of genetic factors in SCI.

Nociceptive and Transcriptomic Responses in a Swine Diabetic Wound Model Treated With a Topical Angiotensin 1 Receptor Antagonist.

BACKGROUND: Painful, treatment-resistant wounds are prevalent among diabetic patients and significantly affect health-related quality of life (HRQOL). Topical treatments may help alleviate pain without risk of dependence or side effects. However, there is a lack of topical wound compounds targeting pain-specific receptors. One possible target is proinflammatory angiotensin 1 receptor (AT1R), which is upregulated in diabetic skin and has been implicated in nociception. OBJECTIVES: We investigated the effects of topical valsartan, an AT1R antagonist, on pain (nociceptive thresholds) and gene expression changes (transcriptomics) in a swine model of diabetic wounds. METHODS: Eight wounds were surgically induced in diabetic, hyperglycemic Yucatan miniature swine ( n = 4). Topical AT1R antagonist was applied to wounds on one side and vehicle on the other side. Nocifensive testing was conducted at baseline and then weekly, beginning 7 days after wound induction. Mechanical and thermal stimuli were applied to the wound margins until a nocifensive reaction was elicited or a predetermined cutoff was reached. After 7 weeks of testing, tissue from the dorsal horn, dorsal root ganglion, and wounds were sequenced and analyzed with DESeq2. Unbiased pathway analyses using Metascape were conducted on differentially expressed genes. RESULTS: There was no significant difference in mechanical tolerance threshold between AT1R antagonist-treated and vehicle-treated wounds ( p = .106). Thermal tolerance was significantly higher in AT1R antagonist-treated wounds compared to vehicle-treated ( p = .015). Analysis of differentially expressed genes revealed enriched pathways of interest: interleukin-18 signaling in dorsal horn laminae IV-V and sensory perception of mechanical stimulus in wound tissue. DISCUSSION: In this study, wounds modeling diabetic ulcers were created in hyperglycemic swine and treated with a topical AT1R antagonist. AT1R-antagonist-treated wounds had a higher tolerance threshold than vehicle-treated wounds for thermal hyperalgesia, but not mechanical allodynia. Pathway analyses of differentially expressed genes revealed several pathways of interest for future pain research. Although further studies are needed to confirm the findings, this study can improve nursing care by providing information about a potential future treatment that may be used to decrease pain and improve HRQOL in patients with diabetic wounds.

Differential Gene Expression in Pain-Related Genes are not Affected by the Presence of Dementia.

BACKGROUND: Prior work has demonstrated differences in the transcriptome between those with and without chronic musculoskeletal pain. AIMS: The aim of this study was to explore whether pain-related gene expression is similar between individuals with and without dementia. DESIGN: This was a descriptive study using a one-time assessment. SETTINGS: PARTICIPANTS/SUBJECTS: A total of 20 older adults living in a continuing care retirement community, 50% of whom had dementia were inlcuded in this study. All were female and the mean age of participants was 89 (SD = 6). METHODS: Pain was evaluated based on the PROMIS Pain Intensity Short Form 3a. Whole blood was collected by venipuncture into Tempus vacutainer tubes (3 ml) and the RNA was extracted at the Translational Genomics Laboratory at the University of Maryland Baltimore. Analyses included a differential expression analysis, a weighted gene co-expression network analysis, and a pathway enrichment analysis. RESULTS: Eighty-three genes were differentially expressed between individuals with and without pain (p <.05). After normalizing gene counts and removing the low expressed genes, 18,028 genes were left in the final analysis. There was no clustering of the samples related to study variables of pain or dementia. CONCLUSION: The findings from this study provided some preliminary support that pain-related gene expression is similar between individuals with and without dementia.

Dietary Composition, Meal Timing, and Cancer-Related Fatigue: Insights From the Women's Healthy Eating and Living Study.

BACKGROUND: Cancer-related fatigue is difficult to treat, and dietary interventions are promising yet underused. OBJECTIVE: We explored associations between dietary patterns and fatigue, and the effect of a dietary intervention versus control on fatigue using Women's Healthy Eating and Living study data, plus mediators and moderators of the intervention effect. METHODS: The Women's Healthy Eating and Living study was a randomized controlled trial among early-stage breast cancer survivors. The 4-year intervention encouraged fruits, vegetables, fiber, and 15% to 20% calories from fat. Fatigue outcomes included a 9-item energy scale and a single-item tiredness question. Dietary quality was estimated using a modified Healthy Eating Index (24-hour dietary recall) and serum carotenoid concentrations. Nutrient timing was obtained from 4-day food logs. RESULTS: Among 2914 total participants, lower body mass index was associated with less tiredness and more energy at baseline (P < .001 for both). Earlier start and end times for daily eating windows were associated with less tiredness (P = .014 and P = .027, respectively) and greater energy (P = .006 and P = .102, respectively). The intervention did not lead to improvements in fatigue on average (P > .125). However, the intervention was more effective for participants who were younger, had fewer comorbidities, and did not have radiation treatment. Mediators included increases in serum carotenoids, increases in the modified Healthy Eating Index, and weight loss/maintenance. CONCLUSION: Diet quality and earlier eating windows were associated with less fatigue. IMPLICATIONS FOR PRACTICE: Programs that encourage high diet quality and a morning meal and discourage nighttime eating should be tested for efficacy in reducing cancer-related fatigue in survivorship.

Feasibility and Acceptability of an Online Yoga Study Among Individuals with Irritable Bowel Syndrome (IBS).

Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain that is often comorbid with psychiatric disorders and other pain-related conditions. The practice of yoga improves symptoms among patients with IBS, although the virtual delivery of yoga in this patient population remains understudied. The purpose of this article is to report feasibility and acceptability of a 6-week pilot yoga intervention among IBS and healthy control participants, which was transitioned to an online format in response to the COVID-19 pandemic. Participants attended 3 virtual study visits and received 60-minute private yoga sessions twice weekly for 6 weeks via Zoom. Sixteen females (n = 8 in IBS group, n = 8 in control group) with a mean age of 34.7 identified as White (87.5%) and Asian (12.5%). All participants attended all 3 study visits; 14 participants attended 12 yoga sessions, 1 attended 11, and 1 attended 9. At the end of the study, 81.3% of participants strongly agreed that participating in the online study was beneficial and convenient, and 87.5% strongly agreed that participating in the online yoga program was beneficial. Our online study and yoga intervention was feasible and acceptable; future studies with larger and more diverse populations will be conducted to investigate health effects among individuals with IBS.

Neurophysiological and transcriptomic predictors of chronic low back pain: Study protocol for a longitudinal inception cohort study.

Chronic low back pain is one of the most common, costly, and debilitating pain conditions worldwide. Increased mechanistic understanding of the transition from acute to chronic low back and identification of predictive biomarkers could enhance the clinical assessment performed by healthcare providers and enable the development of targeted treatment to prevent and/or better manage chronic low back pain. This study protocol was designed to identify the neurological and transcriptomic biomarkers predictive of chronic low back pain at low back pain onset. This is a prospective descriptive longitudinal inception cohort study that will follow 340 individuals with acute low back pain and 40 healthy controls over 2 years. To analyze the neurophysiological and transcriptomic biomarkers of low back pain, the protocol includes psychological and pain-related survey data that will be collected beginning within 6 weeks of low back pain onset (baseline, 6, 12, 24, 52 weeks, and 2 years) and remotely at five additional time points (8, 10, 16, 20 weeks, and 18 months). Quantitative sensory testing and collection of blood samples for RNA sequencing will occur during the six in-person visits. The study results will describe variations in the neurophysiological and transcriptomic profiles of healthy pain-free controls and individuals with low back pain who either recover to pain-free status or develop chronic low back pain.

Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, especially in those CIPN types where analgesia and neuroinflammation modulation might be beneficial. In fact, several clinical trials are ongoing with the specific aim to better investigate the changes in endocannabinoid levels induced by systemic chemotherapy and the possible role of endocannabinoid system modulation to provide relief from CIPN symptoms, a hypothesis supported by preclinical evidence but never consistently demonstrated in patients. Interestingly, endocannabinoid system modulation might be one of the mechanisms at the basis of the reported efficacy of exercise and physical therapy in CIPN patients. This possible virtuous interplay will be discussed in this review.

Prior Night Sleep Affects Next-Day Pain Interference Among Community-Dwelling Older Adults With Lower Extremity Chronic Pain.

Emergent work suggests that sleep is a robust biobehavioral predictor of pain; however, it remains unclear how sleep is prospectively linked to pain on a day-to-day basis among older adults. The current prospective study examined how sleep duration (total sleep time), quality (sleep efficiency, wake after sleep onset), and late and irregular sleep timing influenced next-day pain perception among community-dwelling older adults (N = 10; 65 matched observations) with lower extremity chronic pain over 1 week. Multilevel modeling estimated the association between sleep (Actigraph GT9X Link) and pain perception (Brief Pain Inventory Short Form). Increased wake after sleep onset (B = 0.19, p = 0.04), sleep variability (B = 0.02, p = 0.01), and later midsleep time (B = 0.40, p < 0.05) were associated with increased pain interference the following day. Findings support the idea that timely sleep interventions may reduce the effect of poor sleep on next-day pain in older adults. [Research in Gerontological Nursing, 14(4), 173-179.].

Quantitative Sensory Testing Across Chronic Pain Conditions and Use in Special Populations.

Chronic pain imposes a significant burden to the healthcare system and adversely affects patients' quality of life. Traditional subjective assessments, however, do not adequately capture the complex phenomenon of pain, which is influenced by a multitude of factors including environmental, developmental, genetic, and psychological. Quantitative sensory testing (QST), established as a protocol to examine thermal and mechanical sensory function, offers insight on potential mechanisms contributing to an individual's experience of pain, by assessing their perceived response to standardized delivery of stimuli. Although the use of QST as a research methodology has been described in the literature in reference to specific pain populations, this manuscript details application of QST across a variety of chronic pain conditions. Specific conditions include lower extremity chronic pain, knee osteoarthritis, chronic low back pain, temporomandibular joint disorder, and irritable bowel syndrome. Furthermore, we describe the use of QST in placebo/nocebo research, and discuss the use of QST in vulnerable populations such as those with dementia. We illustrate how the evaluation of peripheral sensory nerve function holds clinical promise in targeting interventions, and how using QST can enhance patient education regarding prognostic outcomes with particular treatments. Incorporation of QST methodology in research investigations may facilitate the identification of common mechanisms underlying chronic pain conditions, guide the development of non-pharmacological behavioral interventions to reduce pain and pain-related morbidity, and enhance our efforts toward reducing the burden of chronic pain.

Invariance of the PAINAD Scale Between the Black and White Residents Living With Dementia.

The purpose of this study was to test the reliability and validity of the Pain Assessment in Advanced Dementia (PAINAD) and particularly consider whether or not this measure was invariant when used among the Black and White residents. Baseline data from an implementation study testing that included a sample of 553 residents, 30% of who were Black, from 55 nursing were included in this study. The Winsteps statistical program was used to perform the Rasch analysis and evaluate the reliability and validity of the measure based on internal consistency, infit and outfit statistics, mapping, and a differential item functioning (DIF) analysis. The AMOS statistical program was used for confirmatory factor analysis. The findings supported the reliability and validity of the PAINAD when used with these individuals and demonstrated that there was no evidence of invariance between the Black and White residents. All the items fit the model, but there was not a good spread of the items across the pain level of the participants. The majority of the participants (75%) were so low in pain signs or symptoms that they could not be differentiated. Based on the clinical practice and observations, it is recommended that additional items can be added to the measure such as observing the individual for evidence of resisting care, retropulsion when trying to stand, hitting or kicking when turning in bed, hitting or kicking when transferring from bed to chair, hitting or kicking when ambulating, or hitting or kicking when raising arms, less engagement with others, and decreased participation in the activities previously enjoyed.

Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain.

Brain-derived neurotrophic factor (BDNF), a major focus for regenerative therapeutics, has been lauded for its pro-survival characteristics and involvement in both development and recovery of function within the central nervous system (CNS). However, studies of tyrosine receptor kinase B (TrkB), a major receptor for BDNF, indicate that certain effects of the TrkB receptor in response to disease or injury may be maladaptive. More specifically, imbalance among TrkB receptor isoforms appears to contribute to aberrant signaling and hyperpathic pain. A truncated isoform of the receptor, TrkB.T1, lacks the intracellular kinase domain of the full length receptor and is up-regulated in multiple CNS injury models. Such up-regulation is associated with hyperpathic pain, and TrkB.T1 inhibition reduces neuropathic pain in various experimental paradigms. Deletion of TrkB.T1 also limits astrocyte changes in vitro, including proliferation, migration, and activation. Mechanistically, TrkB.T1 is believed to act through release of intracellular calcium in astrocytes, as well as through interactions with neurotrophins, leading to cell cycle activation. Together, these studies support a potential role for astrocytic TrkB.T1 in hyperpathic pain and suggest that targeted strategies directed at this receptor may have therapeutic potential.

Transition From Acute to Chronic Pain in Lower Extremity Fracture Patients: A Pain Phenotyping Protocol.

BACKGROUND: Traumatic injury is a major source of chronic pain, particularly for individuals with traumatic fracture of the fibula and/or tibia (lower extremity fracture [LEFx]). Although several factors (e.g., older age, being female, high pain intensity at time of initial injury) have been identified as risk factors for chronic pain associated with LEFx. Comprehensive biopsychosical models to predict the odds of transitioning from acute to chronic pain after LEFx are needed to better understand the underlying processes, predict risk for chronic pain, and develop personalized therapies for individuals at higher risk for developing chronic pain. OBJECTIVE: The aim of the study was to outline the study design that will be used to examine the physiological, psychological, and genetic/genomic variables-models that predict the transition from acute to chronic pain after LEFx. METHOD: This prospective descriptive cohort study will enroll 240 participants with a fibula and/or tibia fracture and 40 controls with no LEFx. Data will be collected during an in-hospital baseline visit, five in-person clinic visits (6 weeks, 12 weeks, 24 weeks, 52 weeks, and 24 months), and seven online between-visit surveys (2 weeks, 4 weeks, 8 weeks, 10 weeks, 16 weeks, 20 weeks, and 18 months) from participants with LEFx and at concordant intervals from controls. Measures will consist of 19 questionnaires characterizing pain and psychological status, neurophysiological testing for peripheral sensory nerve function, and peripheral blood samples collections for RNA sequencing. Illumina standard protocols will be used to sequence RNA, and read counts will be used to measure gene expression. ANALYSIS: Direct-entry, multiple logistic regression will be used to produce odds ratios expressing the relative risk on each explanatory variable when controlling for other predictors/covariates in the model. CONCLUSION: This study is one of the first to longitudinally characterize the biopsychosocial variables associated with a clinically relevant problem of the transition from acute to chronic posttraumatic fracture pain in individuals with LEFx. Results from this study will be used to construct predictive risk models of physiological, psychological, and genetic/genomic variables associated with increased risk for transitioning from acute to chronic pain status after LEFx. This work will lead to a better understanding of the trajectory of pain and relevant variables over time; initiate a better understanding of variables associated with risk for transitioning from acute to chronic pain; and, in the future, could provide a foundation for the identification of novel therapeutic targets to improve the outcomes of individuals with LEFx.

Whole blood transcriptomic profiles can differentiate vulnerability to chronic low back pain.

The mechanisms underlying the transition from acute to chronic pain remain unclear. Here, we sought to characterize the transcriptome associated with chronic low back pain as well as the transcriptome of the transition from acute to chronic low back pain. For the analysis, we compared the whole blood transcriptome of: (a) patients at the onset of low back pain who no longer had pain within 6 weeks after onset (acute) with patients who developed chronic low back pain at 6 months (chronic T5); and, (b) patients at the onset of low back pain (chronic T1) who developed chronic pain at 6 months with healthy pain-free (normal) controls. The majority of differentially expressed genes were protein coding. We illustrate a unique chronic low back pain transcriptome characterized by significant enrichment for known pain genes, extracellular matrix genes, and genes from the extended major histocompatibility complex (MHC) genomic locus. The transcriptome of the transition from acute to chronic low back pain was characterized by significant upregulation of antigen presentation pathway (MHC class I and II) genes and downregulation of mitochondrial genes associated with oxidative phosphorylation, suggesting a unique genomic signature of vulnerability to low back pain chronicity.

Racial/ethnic differences in experimental pain sensitivity and associated factors - Cardiovascular responsiveness and psychological status.

This study evaluated the contributions of psychological status and cardiovascular responsiveness to racial/ethnic differences in experimental pain sensitivity. The baseline measures of 3,159 healthy individuals-non-Hispanic white (NHW): 1,637, African-American (AA): 1,012, Asian: 299, and Hispanic: 211-from the OPPERA prospective cohort study were used. Cardiovascular responsiveness measures and psychological status were included in structural equation modeling based mediation analyses. Pain catastrophizing was a significant mediator for the associations between race/ethnicity and heat pain tolerance, heat pain ratings, heat pain aftersensations, mechanical cutaneous pain ratings and aftersensations, and mechanical cutaneous pain temporal summation for both Asians and AAs compared to NHWs. HR/MAP index showed a significant inconsistent (mitigating) mediating effect on the association between race/ethnicity (AAs vs. NHWs) and heat pain tolerance. Similarly, coping inconsistently mediated the association between race/ethnicity and mechanical cutaneous pain temporal summation in both AAs and Asians, compared to NHWs. The factor encompassing depression, anxiety, and stress was a significant mediator for the associations between race/ethnicity (Asians vs. NHWs) and heat pain aftersensations. Thus, while pain catastrophizing mediated racial/ethnic differences in many of the QST measures, the psychological and cardiovascular mediators were distinctly restrictive, signifying multiple independent mechanisms in racial/ethnic differences in pain.

Precision health: Advancing symptom and self-management science.

BACKGROUND: Precision health considers individual lifestyle, genetics, behaviors, and environment context and facilitates interventions aimed at helping individuals achieve well-being and optimal health. PURPOSE: To present the Nursing Science Precision Health (NSPH) Model and describe the integration of precision health concepts within the domains of symptom and self-management science as reflected in the National Institute of Nursing Research P30 Centers of Excellence and P20 Exploratory Centers. METHODS: Center members developed the NSPH Model and the manuscript based on presentations and discussions at the annual NINR Center Directors Meeting and in follow-up telephone meetings. DISCUSSION: The NSPH Model comprises four precision components (measurement; characterization of phenotype including lifestyle and environment; characterization of genotype and other biomarkers; and intervention target discovery, design, and delivery) that are underpinned by an information and data science infrastructure. CONCLUSION: Nurse scientist leadership is necessary to realize the vision of precision health as reflected in the NSPH Model.

Change in Pain Score after Administration of Analgesics for Lower Extremity Fracture Pain during Hospitalization.

BACKGROUND: Effective acute pain management following injury is critical to improve short-and long-term patient outcomes. Analgesics can effectively reduce pain intensity, yet half of injury patients report moderate to severe pain during hospitalization. PURPOSE: The primary aim of this study was to identify the analgesic, different analgesic combinations, or analgesic and adjuvant analgesic combination that generated the largest percent change from pre- to post-analgesic pain score. DESIGN: This was a descriptive retrospective cohort study of 129 adults admitted with lower extremity fractures to a trauma center. METHODS: Name, dose, and frequency of analgesics and adjuvant analgesics administered from admission to discharge were collected from medical records. Percent change was calculated from pain scores documented on the 0-10 numeric rating scale. RESULTS: The analgesic with largest percent change from pre- to post-administration pain score was hydromorphone 2 mg IV (53%) for the emergency department and morphine 4 mg IV (54%) for the in-patient unit. All analgesics administered in the emergency department and ∼50% administered on the in-patient unit produced a minimal (15%) decrease in pain score. CONCLUSIONS: This study revealed that few analgesics administered in the emergency department and the in-patient unit to patients with lower extremity fractures provide adequate pain relief. In the emergency department, all analgesics administered resulted in at least minimal improvement of pain. On the in-patient unit 13 analgesic doses resulted at least minimal improvement in pain while nine doses did not even reach 20% change in pain. Findings from this study can be used guide the treatment of fracture pain in the hospital.

Global Transcriptomic Profile of Dorsal Root Ganglion and Physiological Correlates of Cisplatin-Induced Peripheral Neuropathy.

BACKGROUND: Multiple cell signaling pathways are implicated in the development, progression, and persistence of cisplatin-induced peripheral neuropathy. Although advances have been made in terms of understanding specific neurotoxic mechanisms, there are few predictive factors identified that can help inform the clinician approach to symptom prevention or management. OBJECTIVE: We investigate the differential sensitivity to cisplatin-induced peripheral neuropathy and examine the contribution of dorsal root ganglion (DRG) transcriptional profiles across two inbred strains of mice. METHODS: Cisplatin (4 mg/kg intraperitoneal or vehicle control) was administered twice a week for 4 weeks to adult female C57BL/6J and A/J mice-the C57BL/6J strain of mice characterized by a robust mechanical allodynia and the A/J with a mild largely resistant allodynia phenotype. Peripheral nerve conduction velocities (NCVs), electrophysiological evaluation of wide dynamic range (WDR) neurons, morphological examination of DRG neurons, and microarray analysis of spinal cord tissues were compared across the 4 weeks. RESULTS: The A/J strain presents with an early, mild nocifensive response to cisplatin with reduced neuronal activity in WDR neurons and small changes in cross-sectional nucleus size in DRG neurons at 4 weeks. The more nocifensive-sensitive C57BL/6J strain presents with no early changes in WDR neuron responsiveness; however, there were significant changes in DRG size. Both strains demonstrate a drop in NCV after 4 weeks of treatment, with the greatest reduction present in the A/J strain. Transcriptome data implicate neuroimmune modulation in the differential response to cisplatin in the DRGs of A/J and C57BL/6J mice. DISCUSSION: Nocifensive responses in both strains implicate involvement of small myelinated and unmyelinated fibers in neurotoxic cisplatin response, whereas reductions in NCV reflect involvement of the largest myelinated fibers in the peripheral nerves. Microarray data analysis identifies neuropathy-relevant gene sets with differential activation of pathways, suggesting a role for antigen presentation in the differential neurotoxic response to cisplatin across strains. Further research is indicated to determine the relative contributions of each of these potential pathological mechanisms to both the neurotoxic response to cisplatin and to the potential for targeted therapy.

Biomarkers as Common Data Elements for Symptom and Self-Management Science.

PURPOSE: Biomarkers as common data elements (CDEs) are important for the characterization of biobehavioral symptoms given that once a biologic moderator or mediator is identified, biologically based strategies can be investigated for treatment efforts. Just as a symptom inventory reflects a symptom experience, a biomarker is an indicator of the symptom, though not the symptom per se. The purposes of this position paper are to (a) identify a "minimum set" of biomarkers for consideration as CDEs in symptom and self-management science, specifically biochemical biomarkers; (b) evaluate the benefits and limitations of such a limited array of biomarkers with implications for symptom science; (c) propose a strategy for the collection of the endorsed minimum set of biologic samples to be employed as CDEs for symptom science; and (d) conceptualize this minimum set of biomarkers consistent with National Institute of Nursing Research (NINR) symptoms of fatigue, depression, cognition, pain, and sleep disturbance. DESIGN AND METHODS: From May 2016 through January 2017, a working group consisting of a subset of the Directors of the NINR Centers of Excellence funded by P20 or P30 mechanisms and NINR staff met bimonthly via telephone to develop this position paper suggesting the addition of biomarkers as CDEs. The full group of Directors reviewed drafts, provided critiques and suggestions, recommended the minimum set of biomarkers, and approved the completed document. Best practices for selecting, identifying, and using biological CDEs as well as challenges to the use of biological CDEs for symptom and self-management science are described. Current platforms for sample outcome sharing are presented. Finally, biological CDEs for symptom and self-management science are proposed along with implications for future research and use of CDEs in these areas. FINDINGS: The recommended minimum set of biomarker CDEs include pro- and anti-inflammatory cytokines, a hypothalamic-pituitary-adrenal axis marker, cortisol, the neuropeptide brain-derived neurotrophic factor, and DNA polymorphisms. CONCLUSIONS: It is anticipated that this minimum set of biomarker CDEs will be refined as knowledge regarding biologic mechanisms underlying symptom and self-management science further develop. The incorporation of biological CDEs may provide insights into mechanisms of symptoms, effectiveness of proposed interventions, and applicability of chosen theoretical frameworks. Similarly, as for the previously suggested NINR CDEs for behavioral symptoms and self-management of chronic conditions, biological CDEs offer the potential for collaborative efforts that will strengthen symptom and self-management science. CLINICAL RELEVANCE: The use of biomarker CDEs in biobehavioral symptoms research will facilitate the reproducibility and generalizability of research findings and benefit symptom and self-management science.

Precision Health: Use of Omics to Optimize Self-Management of Chronic Pain in Aging.

Chronic pain has become a public health epidemic based on the number of Americans affected and its associated health care costs. Unfortunately, there are few efficacious treatments to manage chronic pain and as the population of older adults and centenarians who are at high risk for chronic pain continues to grow, the chronic pain epidemic will continue to worsen unless new therapeutic strategies are discovered. In the current era of precision medicine, there is a major emphasis being placed on the use of self-management and omics to discover new therapeutic targets and design treatment strategies that are tailored to the individual patient. This commentary discusses the current state of the science related to omics and self-management of chronic pain in older adults, the role of gerontological nurses in this process, and future directions. [Res Gerontol Nurs. 2018; 11(1):7-13.].