Acute postoperative pain impact trajectories and factors contributing to trajectory membership.

BACKGROUND: Ongoing postoperative pain assessments are vital to optimizing pain management and attenuating the development of poor health outcomes after surgery. This study aimed to characterize acute multidimensional trajectories of pain impact on physical function, sleep, mood, and stress and to examine clinical characteristics and demographics associated with trajectory membership. Additionally, this study compared levels of pain intensity and prescription opioid use at 2 weeks and 1 month postoperatively across acute symptom trajectories. METHODS: Participants (N = 285) undergoing total knee arthroplasty, total hip arthroplasty, and spinal fusion procedures were recruited for this multisite prospective observational study. Longitudinal, joint k-means clustering was used to identify trajectories based on pain impact on activity, sleep, mood, and stress. RESULTS: Three distinct pain impact trajectories were observed: Low (33.7%), Improving (35.4%), and Persistently High (30.9%). Participants in the Persistently High impact trajectory reported pain interfering moderately to severely with activity, sleep, mood, and stress. Relative to other trajectories, the Persistently High impact trajectory was associated with greater postoperative pain at 1 month postoperatively. Preoperatively, participants in the Persistently High impact trajectory reported worse Pain Catastrophizing Scale scores and PROMIS Pain Interference, PROMIS Anxiety, and PROMIS Social Isolation scores than did participants presenting with other trajectories. No statistical differences in opioid use were observed across trajectories. CONCLUSIONS: Variation in acute postoperative pain impact on activity, sleep, mood, and stress exists. Given the complex nature of patients' postoperative pain experiences, understanding how psychosocial presentations acutely change throughout hospitalization could assist in guiding clinicians' treatment choices and risk assessments.

Patterns of Change in Pain-related Physical, Mental, and Social Health Outcomes in a Military Population.

OBJECTIVE: Military persons frequently experience pain conditions stemming from noncombat and combat injuries. This study assessed the patterns of change over time and the associations of pain intensity and interference with physical, mental, and social health domains in a military sample. METHODS: A secondary analysis of Pain Assessment Screening Tool and Outcomes Registry (PASTOR) was conducted using data collected over 10 months. Participants selected for analysis completed ≥3 assessments with an interval of ≥14 days between assessments. The Defense and Veterans Pain Rating Scale (DVPRS) measured average and worst pain intensity, and Patient-Reported Outcomes Measurement Information System (PROMIS®) T-scores measured pain and health outcomes. RESULTS: The sample (N = 190) majority reported being active duty (96%); serving in the U.S. Army (93%); and being enlisted (86%). The percent difference from assessment one to assessment three showed improvement for DVPRS average pain (-4.85%) and worst pain (-2.16%), and PROMIS Pain Interference T-score (-1.98%). Improvements were observed for all PROMIS outcomes except depression. The Defense and Veterans Pain Rating Scale average and worst pain intensity and PROMIS pain interference were strongly correlated with physical function. Multilevel models showed that an increase in average and worst pain, and pain interference were associated with a decrease in satisfaction with social roles. CONCLUSION: Analysis identified patterns of change over time in physical, mental, and social health outcomes, as well as associations important to understanding the complexities of pain. This work has implications for pain management nursing in ambulatory settings where ongoing collection and analyses of multivariable outcomes data can inform clinical care.

Multidimensional Perioperative Recovery Trajectories in a Mixed Surgical Cohort: A Longitudinal Cluster Analysis Utilizing National Institutes of Health Patient-Reported Outcome Measurement Information System Measures.

BACKGROUND: Pain trajectories have been described in numerous surgical settings where preoperative characteristics have been used to predict trajectory membership. Suboptimal pain intensity trajectories have been linked to poor longitudinal outcomes. However, numerous biopsychosocial modulators of postoperative pain may also have distinct longitudinal trajectories that may inform additional targets to improve postoperative recovery. METHODS: Patients undergoing total joint arthroplasty, thoracic surgery, spine surgery, major abdominal surgery, or mastectomy completed Patient Reported Outcome Measurement Information System (PROMIS) measures and additional scales preoperatively and at 1 week, 2 weeks, 1 month, 3 months, and 6 months postoperatively. A k-means clustering for longitudinal data was utilized to explore and describe distinct pain impact (PROMIS Pain Interference and Physical Function) trajectories and associated changes in additional biopsychosocial measures. Follow-up analyses examined participant demographics and clinical characteristics associated with trajectory memberships. RESULTS: Three postoperative biopsychosocial symptom clusters were identified across all patients (n = 402): low (35%), average (47%), and high (18%) performance cluster trajectories. Participants undergoing total knee arthroplasty (TKA), spinal surgery, reporting presurgical opioid use, and higher pain catastrophizing scale scores were found to be associated with the low performance trajectory. Patients within the low performance trajectory, while demonstrating small improvements by 6 months, remained mild to moderately impaired in both pain impact and physical health outcomes. Alternatively, participants in the average performance trajectory demonstrated improvement in pain impact to population norms compared to baseline and demonstrated continued improvement across physical and psychological outcomes. Patients within the high performance cluster started within population norms across all measures at baseline and returned to baseline or exceeded baseline values by 6 months postoperatively. Self-reported opioid utilization was significantly higher in the low performance cluster across all time points. While a larger proportion of average performance patients reported opioid utilization during the first postoperative month compared to the high performance cluster, no differences were detected at 6 months postoperatively between these 2 clusters. CONCLUSIONS: These pain impact trajectories build upon previous unidimensional pain intensity trajectories and suggest that additional distinct biopsychosocial measures may have unique trajectories related to cluster assignment. Additionally, these findings highlight the importance of continued pain impact surveillance through the perioperative recovery period to detect patients at risk of experiencing a poor trajectory and subsequently poor longitudinal health outcomes.

Changes in actigraphy metrics associated with PROMIS measures after orthopaedic surgery.

AIM: This study examined the feasibility of integrating actigraphy devices into orthopaedic surgical settings to assess the concurrent validity between objective actigraphy data and PROMIS measures. Additionally, the association between changes in actigraphy data and longitudinal changes in PROMIS measures was examined. METHODS: Data were collected from 17 participants using actigraphy devices the week prior to and after orthopaedic surgery from 02/2019 to 03/2020. Participants completed PROMIS measures (Physical Function, Sleep Disturbance, Pain Interference) preoperatively and up to 6 months postoperatively. Nonparametric correlations (rs ) assessed for concurrent validity. Linear mixed-effects models examined the association between changes in actigraphy data and PROMIS measures. RESULTS: Prolonged wake after sleep onset was associated with increased sleep disturbances (rs = 0.49; p = 0.045) and pain interference (rs = 0.51; p = 0.04). Changes in pain interference were correlated with increased awakenings (rs = 0.54; p = 0.03). Increased wake after sleep onset was associated with worsening sleep disturbance (ß = 0.12; p = 0.01) and pain interference scores over the postoperative period (ß = 0.12; p = 0.02). CONCLUSIONS: This study is among the first to examine changes in objective actigraphy data and longitudinal PROMIS measures following orthopaedic surgery and illustrates the feasibility of incorporating actigraphy into surgical settings to evaluate postoperative recovery.

Implementation of the Uniformed Services University Pain Registry Biobank: A Military and Veteran Population-Focused Biobank and Registry.

OBJECTIVE: The objective of this overview is to discuss the development, implementation, data content, and structure of the Uniformed Services University Pain Registry Biobank. Additionally, procedures and policies for accessing samples for pain-related research purposes are detailed. DESIGN: Cross-sectional overview. SETTING: Multiple military treatment facilities. SUBJECTS: Adult beneficiaries seeking care within the Military Health System. METHODS: Participants complete a baseline battery of biopsychosocial survey measures, including Patient-Reported Outcomes Measurement Information System (PROMIS®) measures, and provide biological samples (e.g., blood and saliva). Relevant health history, including medications and surgical history, is extracted from medical records. During the course of the subsequent year, enrolled participants complete surveys and provide biological samples at 3 months, 6 months, and 12 months. Thereafter, participants are contacted once annually to complete self-reported assessments and provide biological samples. RESULTS: In the first year alone, 86 subjects have participated in the Uniformed Services University Pain Registry Biobank and provided 390 observations (e.g., biological samples and biopsychosocial patient-reported outcomes). The Uniformed Services University Pain Registry Biobank's integration of biological samples, patient-reported outcomes, and health record data over a longitudinal period across a diverse sample recruited from multiple military facilities addresses many of the limitations faced by other pain-related registries or biorepositories. CONCLUSIONS: The Uniformed Services University Pain Registry Biobank will serve as a platform for conducting research closely aligned with the Federal Pain Research Strategy. The inclusion of active duty service members, beneficiaries, and civilians living with and without acute or chronic pain provides a unique data repository for all investigators interested in advancing pain science.

Differential Pain Presentations Observed across Post-Traumatic Stress Disorder Symptom Trajectories after Combat Injury.

OBJECTIVE: This study evaluated the association between pain outcomes and post-traumatic stress disorder (PTSD) symptom trajectories after combat-related injury, while adjusting for receipt of regional anesthesia (RA) soon after injury. METHODS: The PTSD symptom trajectories of N = 288 combat-injured service members were examined from within a month of injury up to two-years after. Linear mixed-effects models evaluated the association between PTSD symptom trajectories and average pain and pain interference outcomes while adjusting for receipt of RA during combat casualty care. RESULTS: Four PTSD trajectories were characterized: resilient, recovering, worsening, and chronic. Differential pain presentations were associated with PTSD symptom trajectories, even after adjusting for receipt of RA. Compared to those with a resilient PTSD symptom trajectory, individuals presenting with chronic PTSD trajectories were estimated to experience average pain scores 2.61 points higher (95% CI: 1.71, 3.14). Participants presenting with worsening (ß = 1.42; 95% CI: 0.77, 1.78) and recovering PTSD trajectories (ß = 0.65; 95% CI: 0.09, 1.08) were estimated to experience higher average pain scores than participants with resilient PTSD trajectories. Significant differences in pain interference scores were observed across PTSD trajectories. Receiving RA was associated with improved pain up to two years after injury (ß = -0.31; 95% CI: -0.90, -0.04), however no statistically significant association was detected between RA and PTSD trajectories. CONCLUSIONS: Chronic and worsening PTSD trajectories were associated with greater pain intensity and interference following combat injury even when accounting for receipt of early RA for pain management. These findings underscore the need to jointly assess pain and PTSD symptoms across the trauma care continuum.

A Longitudinal Comparison of Patient-Reported Outcomes Measurement Information System to Legacy Scales in Knee and Shoulder Arthroscopy Patients.

PURPOSE: The purpose of this prospective correlational study was to compare the psychometric properties of the Defense and Veterans Pain Rating Scale (DVPRS) and Patient-Reported Outcomes Measurement Information System (PROMIS) scales with those of traditional legacy scales over a longitudinal postoperative period in patients undergoing arthroscopic procedures. METHODS: Active-duty military personnel undergoing shoulder and knee arthroscopic procedures completed the DVPRS, PROMIS, and legacy scales preoperatively and again at 3 months postoperatively. Rolling correlation coefficients (rrm) were used to assess the concurrent validity between the DVPRS average pain scores and computer adaptive testing PROMIS scales (Anxiety, Depression, Pain Behavior, Pain Interference, Mobility, Sleep Disturbance, Satisfaction With Social Roles, and Upper Extremity Physical Function) and the legacy scales (American Shoulder and Elbow Surgeons [ASES] scale, Shoulder Activity Scale, International Knee Documentation Committee [IKDC] questionnaire, Single Assessment Numeric Evaluation [SANE], Marx Activity Rating Scale, and Veterans RAND 12-Item Health Survey). RESULTS: A total of 121 participants completed the scales preoperatively, 80 completed them at 3 months postoperatively, and 59 (49% of participants) completed them at both times. Rolling correlation coefficients between PROMIS Pain Interference (rrm = -0.41, P = .006), Satisfaction With Social Roles (rrm = 0.56, P < .001), and Upper Extremity (rrm = 0.71, P < .001) scores showed acceptable concurrent validity with ASES scores over a longitudinal postoperative period. DVPRS scores (rrm = -0.69, P = .002) and PROMIS Pain Behavior (rrm = -0.57, P = .018), Pain Interference (rrm = -0.71, P = .001), Sleep Disturbance (rrm = -0.64, P = .005), and Mobility (rrm = 0.65, P = .005) scores showed acceptable concurrent validity with IKDC scores. There was poor correlation between the PROMIS and DVPRS scores and the Single Assessment Numeric Evaluation, Marx Activity Rating Scale, Shoulder Activity Scale, and Veterans RAND 12-Item Health Survey scores. CONCLUSIONS: PROMIS scales measuring physical function, pain presentation, and other health domains showed acceptable concurrent validity with ASES and IKDC scores. By integrating the prospective collection of biopsychosocial PROMIS scales into practice, it is possible for clinicians in orthopaedic settings to assess changes in validated patient-reported outcomes to inform patient-centered care planning throughout the postoperative recovery period. LEVEL OF EVIDENCE: Level II, prospective comparative study (with not all participants completing follow-up).

Ketamine Administration During Hospitalization Is Not Associated With Posttraumatic Stress Disorder Outcomes in Military Combat Casualties: A Matched Cohort Study.

BACKGROUND: Ketamine is routinely used within the context of combat casualty care. Despite early concerns that ketamine administration may be associated with elevated risk of posttraumatic stress disorder (PTSD), more recent evidence suggests no relationship. Because PTSD occurs with regular frequency in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Service Members (SMs) and combat-related injuries are associated with higher likelihood of PTSD, it is important to investigate the relationship between ketamine exposure during inpatient medical and surgical care and PTSD symptoms in OIF/OEF SMs. METHODS: Medical record data from OIF/OEF SMs medically evacuated from combat (N = 1158) included demographic characteristics, injury severity, body areas injured, and PTSD Checklist (PCL) scores. The primary analysis assessed the association between ketamine versus nonketamine exposure on positive PTSD screen (logistic regression) and PCL scores (linear regression) after using 1:1 propensity score matching to adjust for available potential confounding variables. Because there were 2 primary outcomes, the binary positive PTSD screen (yes/no) and continuous PCL score, the significance level was set at P ≤ .025. In sensitivity analyses, propensity scores were used to match ketamine to nonketamine records in a 1:4 ratio, as well as to conduct inverse probability treatment weighting (IPTW). Regressions examining the relationship between ketamine exposure and outcomes were repeated for unconditional, 1:4 matching, and IPTW models. RESULTS: In the sample, 107 received ketamine and 1051 did not. In the logistic regression, the probability of a positive PTSD screen was not significantly different between ketamine versus nonketamine patients (odds ratio [OR] = 1.28; 95% confidence interval [CI], 0.48-3.47; P = .62). In the linear regression, PCL scores were not significantly different between ketamine versus nonketamine patients (mean difference = 1.98 [95% CI, -0.99 to 4.96]; P = .19). The results were consistent in the unconditional, 1:4 matching, and IPTW models. CONCLUSIONS: No differences in PTSD screening risk or symptom levels between ketamine exposed and nonexposed were found. Given the small sample size, wide CIs of the effects, and additional confounds inherent to retrospective studies, future studies are needed to examine the complex relationships between ketamine and psychological symptoms.

Consideration of the Aerosol Transmission for COVID-19 and Public Health.

This article analyzes the available evidence to address airborne, aerosol transmission of the SARS-CoV-2. We review and present three lines of evidence: case reports of transmission for asymptomatic individuals in association with studies that show that normal breathing and talking produce predominantly small droplets of the size that are subject to aerosol transport; limited empirical data that have recorded aerosolized SARS-CoV-2 particles that remain suspended in the air for hours and are subject to transport over distances including outside of rooms and intrabuilding, and the broader literature that further supports the importance of aerosol transmission of infectious diseases. The weight of the available evidence warrants immediate attention to address the significance of aerosols and implications for public health protection.

Predosing Chemical Stability of Admixtures of Propofol, Ketamine, Fentanyl, and Remifentanil.

Admixtures of propofol-ketamine, propofol-ketamine-fentanyl, and propofol-ketamine-remifentanil were subjected to various clinically relevant conditions to study their chemical stability. A novel high-performance liquid chromatography-mass spectrometry method revealed no degradation of any compound by incubation at 37°C, constant mixing, or table-top storage for 6- and 24-hour time periods, except variable recovery of both propofol and fentanyl in the admixtures of propofol-ketamine-fentanyl suggesting possible degradation.

Feasibility of App-Based Postsurgical Assessment of Pain, Pain Impact, and Regional Anesthesia Effects: A Pilot Randomized Controlled Trial.

OBJECTIVE: Postsurgical follow-up calls enable nurses to assess a patient's condition, provide tailored education, and improve the patient's experience. Despite the benefits, barriers to phone-based assessments may include patient nonresponse and lack of time due to demanding clinical schedules. The purpose of this trial was to examine the feasibility and utility of a smartphone app, mCare, for assessing pain, pain impact, and peripheral nerve block effects in patients. DESIGN: Pilot randomized control trial. SETTING AND PATIENTS: Eligible patients at a military treatment facility undergoing same-day surgery were randomized to the mCare group (N = 24) or the standard-of-care telephone (N = 26) group. RESULTS: Outcomes included initial response (assessment completion) rates and participant and nurse satisfaction. There were no differences in the response rates upon initial contact attempt, and patients in both groups reported similar levels of satisfaction and convenience. Nurses reported greater satisfaction with the app compared with standard-of-care telephone calls. CONCLUSIONS: Before wider implementation, further considerations of app-based assessment need to be fully explored.

Identification of Functioning Domains in the Presurgical Period and Their Relationships with Opioid Use and Pain Catastrophizing.

OBJECTIVES: The National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) is a multidimensional screening system evaluating biopsychosocial factors affecting pain and functioning. Using a military sample, the current study 1) examined the structure and domains of the PROMIS, the Defense and Veterans Pain Rating Scale 2.0 (DVPRS), and the Pain Catastrophizing Scale (PCS) within a presurgical setting and 2) examined the relationship of these variables to pre- and postsurgical opioid use. METHODS: This cross-sectional study included 279 adult patients scheduled for surgery at the Walter Reed National Military Medical Center and a validation sample of 79 additional patients from the Naval Medical Center, San Diego. PROMIS, DVPRS, PCS, and opioid use data were collected before surgery. Exploratory factor analysis and confirmatory factor analysis identified the latent structure for the measures. A structural equation model (SEM) examined their relationship to pre- and postsurgical opioid use. RESULTS: Two latent factors represented Psychosocial Functioning (PROMIS Depression, PROMIS Anxiety, and PROMIS Social Isolation) and Pain Impact (DVPRS, PROMIS Pain Interference, PROMIS Physical Functioning). The remaining PROMIS scales did not load onto a single factor. In the SEM, the two latent factors and PCS were significantly related to pre- and postsurgical opioid use. CONCLUSIONS: This study highlights the utility and relative ease of using a convenient multidimensional assessment in presurgical settings. Using such an assessment can help provide targeted interventions for individuals who may be at greatest risk for negative postsurgical outcomes.

Benefits of the Restorative Exercise and Strength Training for Operational Resilience and Excellence Yoga Program for Chronic Low Back Pain in Service Members: A Pilot Randomized Controlled Trial.

OBJECTIVE: To examine the feasibility and preliminary effectiveness of an individualized yoga program. DESIGN: Pilot randomized controlled trial. SETTING: Military medical center. PARTICIPANTS: Patients (N=68) with chronic low back pain. INTERVENTIONS: Restorative Exercise and Strength Training for Operational Resilience and Excellence (RESTORE) program (9-12 individual yoga sessions) or treatment as usual (control) for an 8-week period. MAIN OUTCOME MEASURES: The primary outcome was past 24-hour pain (Defense & Veterans Pain Rating Scale 2.0). Secondary outcomes included disability (Roland-Morris Disability Questionnaire) and physical functioning and symptom burden (Patient-Reported Outcomes Measurement Information System-29 subscales). Assessment occurred at baseline, week 4, week 8, 3-month follow-up, and 6-month follow-up. Exploratory outcomes included the proportion of participants in each group reporting clinically meaningful changes at 3- and 6-month follow-ups. RESULTS: Generalized linear mixed models with sequential Bonferroni-adjusted pairwise significance tests and chi-square analyses examined longitudinal outcomes. Secondary outcome significance tests were Bonferroni adjusted for multiple outcomes. The RESTORE group reported improved pain compared with the control group. Secondary outcomes did not retain significance after Bonferroni adjustments for multiple outcomes, although a higher proportion of RESTORE participants reported clinically meaningfully changes in all outcomes at 3-month follow-up and in symptom burden at 6-month follow-up. CONCLUSIONS: RESTORE may be a viable nonpharmacological treatment for low back pain with minimal side effects, and research efforts are needed to compare the effectiveness of RESTORE delivery formats (eg, group vs individual) with that of other treatment modalities.

Characterizing CD137 upregulation on NK cells in patients receiving monoclonal antibody therapy.

Background: In the era of personalized cancer medicine, identifying techniques for effectively matching patients to efficacious treatments is a critical step in the treatment process. The advent of anti-cancer immunotherapies necessitates novel approaches to biomarker identification beyond traditional genomic profiling. One promising approach is incorporation of nomograms into treatment decisions. Nomograms are prediction tools, based on statistical modeling, designed to predict treatment outcomes. As a first step toward developing a nomogram, we conducted analyses to predict CD137 expression of natural killer cells after monoclonal antibody (mAb) treatment. Patients and methods: Patient, tumor and immune characteristics were collected from 199 patients with breast cancer (N = 62), head/neck cancers (N = 46) and non-Hodgkin's lymphoma (NHL) (N = 91), who were receiving mAb therapy as part of clinical trials. The difference in CD137 expression before and after mAb therapy was assessed by flow cytometry. To evaluate those who respond to mAb therapy via increased CD137 expression, we applied classification and regression trees (CART), multivariable lasso regression tools and Random Forest. Results: The CD137 expression was significantly different for each cancer type [mean (SD): Breast: 6.6 (6.5); Head/Neck: 11.0 (7.0); NHL: 7.5 (7.1), P < 0.0001]. For breast cancer and NHL, FcR polymorphism and baseline CD137 expression were significant predictors of increased CD137 expression; for head/neck cancer, FcR polymorphism and age were significant predictors of increased expression. Conclusions: Our preliminary results suggest that FcR polymorphism, pre-treatment CD137 expression and age are significant predictors of CD137 upregulation in patients. This study demonstrates that the development of a nomogram for therapy response is feasible. Further work validating our models in an independent cohort will provide the next steps in developing a nomogram that may be used to individualize this therapeutic approach for patients (NCT01114256).

The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) Multidimensional Approach to Classifying Acute Pain Conditions.

Objective: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (e.g., pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain. Setting: Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). Methods: As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions. Perspective: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Conclusions: Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

Defining the optimal murine models to investigate immune checkpoint blockers and their combination with other immunotherapies.

The recent success of checkpoint blockers to treat cancer has demonstrated that the immune system is a critical player in the war against cancer. Historically, anticancer therapeutics have been tested in syngeneic mouse models (with a fully murine immune system) or in immunodeficient mice that allow the engraftment of human xenografts. Animal models with functioning human immune systems are critically needed to more accurately recapitulate the complexity of the human tumor microenvironment. Such models are integral to better predict tumor responses to both immunomodulatory agents and directly antineoplastic therapies. In this regard, the development of humanized models is a promising, novel strategy that offers the possibility of testing checkpoint blockers' capacity and their combination with other antitumor drugs. In this review, we discuss the strengths and weaknesses of the available animal models regarding their capacity to evaluate checkpoint blockers and checkpoint blocker-based combination immunotherapy.

Colon distention induces persistent visceral hypersensitivity by mechanotranscription of pain mediators in colonic smooth muscle cells.

Abdominal pain and distention are major complaints in irritable bowel syndrome. Abdominal distention is mainly attributed to intraluminal retention of gas or solid contents, which may cause mechanical stress to the gut wall. Visceral hypersensitivity (VHS) may account for abdominal pain. We sought to determine whether tonic colon distention causes persistent VHS and if so whether mechanical stress-induced expression (mechanotranscription) of pain mediators in colonic smooth muscle cells (SMCs) plays a role in VHS. Human colonic SMCs were isolated and stretched in vitro to investigate whether mechanical stress upregulates expression of the pain mediator cyclooxygenase-2 (COX-2). Rat colon was distended with a 5-cm-long balloon, and gene expression of COX-2, visceromotor response (VMR), and sensory neuron excitability were determined. Static stretch of colonic SMCs induced marked expression of COX-2 mRNA and protein in a force- and time-dependent manner. Subnoxious tonic distention of the distal colon at ∼30-40 mmHg for 20 or 40 min induced COX-2 expression and PGE2 production in colonic smooth muscle, but not in the mucosa layer. Lumen distention also increased VMR in a force- and time-dependent manner. The increase of VMR persisted for at least 3 days. Patch-clamp experiments showed that the excitability of colon projecting sensory neurons in the dorsal root ganglia was markedly augmented, 24 h after lumen distention. Administration of COX-2 inhibitor NS-398 partially but significantly attenuated distention-induced VHS. In conclusion, tonic lumen distention upregulates expression of COX-2 in colonic SMC, and COX-2 contributes to persistent VHS.

Acute Pain Medicine in the United States: A Status Report.

BACKGROUND: Consensus indicates that a comprehensive,multimodal, holistic approach is foundational to the practice of acute pain medicine (APM),but lack of uniform, evidence-based clinical pathways leads to undesirable variability throughout U. S. healthcare systems. Acute pain studies are inconsistently synthesized to guide educational programs. Advanced practice techniques involving regional anesthesia assume the presence of a physician-led, multidisciplinary acute pain service,which is often unavailable or inconsistently applied.This heterogeneity of educational and organizational standards may result in unnecessary patient pain and escalation of healthcare costs. METHODS: A multidisciplinary panel was nominated through the APM Shared Interest Group of the American Academy of Pain Medicine. The panel met in Chicago, IL, in July 2014, to identify gaps and set priorities in APM research and education. RESULTS: The panel identified three areas of critical need: 1) an open-source acute pain data registry and clinical support tool to inform clinical decision making and resource allocation and to enhance research efforts; 2) a strong professional APM identity as an accredited subspecialty; and 3) educational goals targeted toward third-party payers,hospital administrators, and other key stake holders to convey the importance of APM. CONCLUSION: This report is the first step in a 3-year initiative aimed at creating conditions and incentives for the optimal provision of APM services to facilitate and enhance the quality of patient recovery after surgery, illness, or trauma. The ultimate goal is to reduce the conversion of acute pain to the debilitating disease of chronic pain.