A preliminary examination of the effects of childhood abuse and resilience on pain and physical functioning in patients with knee osteoarthritis.

OBJECTIVES: We examined associations of a self-reported history of childhood abuse with pain and physical functioning in patients with knee osteoarthritis (KOA) awaiting total knee arthroplasty (TKA). We also explored the potential moderating effects of positive childhood experiences (PCEs), an index of resilience, on these associations. METHODS: Prior to TKA, participants with KOA awaiting surgery (N = 239) completed self-report measures of adverse childhood experiences (ACEs), PCEs, pain, and physical functioning. We evaluated associations of pain and physical functioning (Brief Pain Inventory [BPI] and Western Ontario and McMaster University of Osteoarthritis Index [WOMAC]) based on the experience of ACEs (childhood abuse), with PCEs (childhood happiness and supportive parental care) as potential moderators. RESULTS: Greater exposure to childhood abuse was positively correlated with BPI pain interference as well as WOMAC pain and functioning scores. Additionally, childhood happiness and supportive parental care moderated the positive associations of childhood abuse with pain and physical functioning; though, surprisingly, the adverse effects of childhood abuse on these outcomes were more pronounced among participants with high levels of childhood happiness and supportive parental care. CONCLUSION: Overall, results show an association between a self-reported history of childhood abuse and pain and functioning in patients with KOA awaiting TKA. However, PCEs did not protect against the negative consequences of childhood abuse in our cohort. Further research is needed to validate these associations and gain a more comprehensive understanding of the complex interplay between childhood abuse and PCEs and their potential influences on pain experiences in adults with chronic pain conditions, including KOA.

The association between changes in clinical pain severity and IL-6 reactivity among patients undergoing total knee Arthroplasty: The moderating role of change in insomnia.

Knee osteoarthritis (KOA) is linked to an enhanced release of interleukin-6 (IL-6). Increased levels of IL-6 are associated with greater pain and insomnia. While total knee arthroplasty (TKA) typically results in the reduction of pain, for a subgroup of patients, pain does not improve. Understanding patients' propensity to upregulate IL-6 may provide insight into variation in the clinical success of TKA for improving pain, and insomnia may play an important modulatory role. We investigated the association between pre- and post-surgical changes in clinical pain and IL-6 reactivity, and whether change in insomnia moderated this association. Patients (n = 39) with KOA came in-person before and 3-months after TKA. At both visits, patients completed validated measures of clinical pain and insomnia, as well as underwent quantitative sensory testing (QST). Blood samples were collected to analyze IL-expression both before and after QST procedures to assess changes in IL-6 in response to QST (IL-6 reactivity). Patients were categorized into two groups based on change in clinical pain from pre- to post-surgery: 1) pain decreased > 2 points (pain improved) and 2) pain did not decrease > 2 points (pain did not improve). Based on this definition, 49 % of patients had improved pain at 3-months. Among patients with improved pain, IL-6 reactivity significantly decreased from pre- to post-surgery, whereas there was no significant change in IL-6 reactivity among those whose pain did not improve. There was also a significant interaction between pain status and change in insomnia, such that among patients whose insomnia decreased over time, improved pain was significantly associated with a reduction in IL-6 reactivity. However, among patients whose insomnia increased over time, pain status and change in IL-6 reactivity were not significantly associated. Our findings suggest that the resolution of clinical pain after TKA may be associated with discernible alterations in pro-inflammatory responses that can be measured under controlled laboratory conditions, and this association may be moderated by perioperative changes in insomnia. Randomized controlled trials which carefully characterize the phenotypic features of patients are needed to understand how and for whom behavioral interventions may be beneficial in modulating inflammation, pain, and insomnia.

Preoperative decreased physical activity is associated with greater postoperative pain: the mediating role of preoperative sleep disturbance.

PURPOSE: Engagement in physical activity (PA) is often associated with better sleep quality and less pain severity among patients diagnosed with breast cancer. However, less research has focused on whether patients' PA prior to breast surgery, including their perceived decrease in PA level, is associated with worse preoperative sleep quality, and subsequently, greater postoperative pain. This longitudinal study investigated whether patients' preoperative PA was associated with their postoperative pain. We also explored whether preoperative sleep disturbance partially mediated the relationship between preoperative PA and postoperative pain. METHODS: Prior to breast surgery, patients self-reported both their overall level of PA and whether they perceived a decrease in their PA since the diagnosis/onset of treatment for cancer. Patients also completed a measure of preoperative sleep disturbance. Two weeks after surgery, patients completed a measure of postoperative surgical-area pain severity. RESULTS: Our results showed that preoperatively perceiving a decrease in PA level was significantly associated with greater preoperative sleep disturbance and postoperative pain. A mediation analysis revealed that the association between preoperative decreased PA and postoperative pain was partially mediated by preoperative sleep disturbance. Notably, patients' overall preoperative level of PA was not related to preoperative sleep disturbance or postoperative pain. CONCLUSION: These findings suggest that maintaining, or even increasing, PA after diagnosis/treatment may be more important than the absolute amount of PA that women engage in during the preoperative period. Potentially, some patients with breast cancer may benefit from a preoperative intervention focused on both maintaining PA and bolstering sleep quality.

Individuals with fibromyalgia report greater pain sensitivity than healthy adults while listening to their favorite music: the contribution of negative affect.

OBJECTIVE: We investigated the impact of favorite music on pain processing among individuals with fibromyalgia. We also examined differences in pain processing between individuals with fibromyalgia and healthy controls (HC) while listening to favorite music and explored whether psychosocial factors contributed to these differences. METHODS: Individuals with fibromyalgia and HC completed baseline psychosocial questionnaires and then underwent quantitative sensory testing (QST) during 3 randomized music conditions (meditative music, favorite music, white noise). Among individuals with fibromyalgia, Friedman tests were used to investigate differences in QST across conditions. Analyses of Covariance were used to examine group (HC vs fibromyalgia) differences in QST during favorite music. Correlations were conducted to explore associations of baseline psychosocial factors with QST during favorite music. Mediation analyses were conducted to explore whether psychosocial factors contributed to greater pain sensitivity among individuals with fibromyalgia compared to HC during favorite music. RESULTS: Individuals with fibromyalgia were less sensitive to pressure pain while listening to their favorite music compared to white noise. Compared to HC, individuals with fibromyalgia reported higher baseline negative affect and lower pain thresholds and tolerances during favorite music. Negative affect partially mediated the relationship between pain status (HC vs fibromyalgia) and pain sensitivity during favorite music. CONCLUSIONS: Individuals with fibromyalgia were less pain sensitive while listening to favorite music than white noise, although they were more sensitive than HC. Greater negative affect endorsed by individuals with fibromyalgia contributed to their greater pain sensitivity. Future studies should explore the impact of favorite music on clinical pain. CLINICAL TRAILS REGISTRATION: This study was registered with ClinicalTrials.gov (NCT04087564) and began on 6/13/2019.

A secondary analysis: the impact of pre-existing chronic pain among patients with cancer presenting to the emergency department with acute pain.

PURPOSE: Patients with cancer may experience pain from cancer itself or its treatment. Additionally, chronic pain (CP) predating a patient's cancer diagnosis may make the etiology of pain less clear and the management of pain more complex. In this brief report, we investigated differences in biopsychosocial characteristics, pain severity, and opioid consumption, comparing groups of cancer patients with and without a history of CP who presented to the emergency department (ED) with a complaint of cancer-related pain. METHODS: This secondary analysis of a prospective cohort study included patients with cancer who presented to the ED with a complaint of pain (≥ 4/10). Sociodemographic, clinical, psychological, and pain characteristics were assessed in the ED and subsequent hospitalization. Mann-Whitney U-, T-, and Chi-square tests were used to compare differences between patients with and without pre-existing CP before cancer. RESULTS: Patients with pre-existing CP had lower income (p = 0.21) and less formal education (p = 0.25) and were more likely to have a diagnosis of depression or substance use disorder (p < 0.01). Patients with pre-existing CP reported significantly greater pain severity in the ED and during hospitalization compared to those without pre-existing CP (p < 0.05), despite receiving greater amounts of opioid analgesics (p = 0.036). CONCLUSION: Identifying a history of pre-existing CP during intake may help identify patients with cancer with difficult to manage pain, who may particularly benefit from multimodal interventions and supportive care. In addition, referral of these patients for the management of co-occurring pain disorders may help decrease the usage of the ED for undertreated pain.

Brief Assessment of Patient Phenotype to Explain Variability in Postsurgical Pain and Opioid Consumption after Cesarean Delivery: Performance of a Novel Brief Questionnaire Compared to Long Questionnaires.

BACKGROUND: Understanding factors that explain why some women experience greater postoperative pain and consume more opioids after cesarean delivery is crucial to building an evidence base for personalized prevention. Comprehensive psychosocial assessment with validated questionnaires in the preoperative period can be time-consuming. A three-item questionnaire has shown promise as a simpler tool to be integrated into clinical practice, but its brevity may limit the ability to explain heterogeneity in psychosocial pain modulators among individuals. This study compared the explanatory ability of three models: (1) the 3-item questionnaire, (2) a 58-item questionnaire (long) including validated questionnaires (e.g., Brief Pain Inventory, Patient Reported Outcome Measurement Information System [PROMIS]) plus the 3-item questionnaire, and (3) a novel 19-item questionnaire (brief) assessing several psychosocial factors plus the 3-item questionnaire. Additionally, this study explored the utility of adding a pragmatic quantitative sensory test to models. METHODS: In this prospective, observational study, 545 women undergoing cesarean delivery completed questionnaires presurgery. Pain during local anesthetic skin wheal before spinal placement served as a pragmatic quantitative sensory test. Postoperatively, pain and opioid consumption were assessed. Linear regression analysis assessed model fit and the association of model items with pain and opioid consumption during the 48 h after surgery. RESULTS: A modest amount of variability was explained by each of the three models for postoperative pain and opioid consumption. Both the brief and long questionnaire models performed better than the three-item questionnaire but were themselves statistically indistinguishable. Items that were independently associated with pain and opioid consumption included anticipated postsurgical pain medication requirement, surgical anxiety, poor sleep, pre-existing pain, and catastrophic thinking about pain. The quantitative sensory test was itself independently associated with pain across models but only modestly improved models for postoperative pain. CONCLUSIONS: The brief questionnaire may be more clinically feasible than longer validated questionnaires, while still performing better and integrating a more comprehensive psychosocial assessment than the three-item questionnaire.

The role of sleep disturbance in reduced accuracy on a divided attention task among patients with fibromyalgia.

Introduction: Patients with fibromyalgia show impaired cognitive performance compared with healthy, pain-free controls. Sleep disturbance, anxiety, and depression are highly prevalent among patients with fibromyalgia, and each is associated with impaired cognitive performance. Yet, limited work has explored whether psychosocial factors contribute to group differences in cognitive performance. Objectives: This secondary data analysis investigated differences in cognitive performance between patients with fibromyalgia and healthy controls, and whether psychosocial factors accounted for these differences. Methods: Adults with fibromyalgia (N = 24) and healthy, pain-free controls (N = 26) completed 2 cognitive tasks and the Patient-Reported Outcomes Measurement Information System sleep disturbance, anxiety, and depression short forms. Independent samples t tests were used to test for differences in cognitive performance between patients with fibromyalgia and healthy controls. Pearson correlations were conducted to examine associations between psychosocial factors and cognitive performance. Psychosocial factors significantly related to cognitive performance were explored as potential mediators of group differences in cognitive performance. Results: Patients with fibromyalgia demonstrated poorer accuracy for divided attention compared with healthy controls, and sleep disturbance mediated this group difference. On the attentional switching task, healthy controls showed a greater switch-cost for accuracy compared with patients with fibromyalgia, but there was no group difference in reaction time. Anxiety and depression were not related to cognitive performance. Conclusion: We found that patients with fibromyalgia reported greater sleep disturbance and, in turn, had poorer accuracy on the divided attention task. Sleep disturbance is modifiable with behavioral interventions, such as cognitive behavioral therapy, and may be a target for improving sleep quality and cognitive performance among patients with fibromyalgia.

Daily pain and opioid administration in hospitalized patients with cancer: the importance of psychological factors, recent surgery, and current opioid use.

ABSTRACT: Pain is common and variable in its severity among hospitalized patients with cancer. Although biopsychosocial factors are well established as modulators of chronic pain, less is known about what patient-level factors are associated with worse pain outcomes among hospitalized cancer patients. This prospective cohort study included patients with active cancer presenting to the emergency department (ED) with pain severity of ≥4/10 and followed pain outcomes longitudinally throughout hospital admission. Baseline demographic, clinical, and psychological factors were assessed on ED presentation, and daily average clinical pain ratings and opioid consumption during hospitalization were abstracted. Univariable and multivariable generalized estimating equation analyses examined associations of candidate biopsychosocial, demographic, and clinical predictors with average daily pain and opioid administration. Among 113 hospitalized patients, 73% reported pain as the primary reason for presenting to the ED, 43% took outpatient opioids, and 27% had chronic pain that predated their cancer. Higher pain catastrophizing ( B = 0.1, P ≤ 0.001), more recent surgery ( B = -0.2, P ≤ 0.05), outpatient opioid use ( B = 1.4, P ≤ 0.001), and history of chronic pain before cancer diagnosis ( B = 0.8, P ≤ 0.05) were independently associated with greater average daily pain while admitted to the hospital. Higher pain catastrophizing ( B = 1.6, P ≤ 0.05), higher anxiety ( B = 3.7, P ≤ 0.05), lower depression ( B = -4.9, P ≤ 0.05), metastatic disease ( B = 16.2, P ≤ 0.05), and outpatient opioid use ( B = 32.8, P ≤ 0.001) were independently associated with higher daily opioid administration. Greater psychological distress, especially pain catastrophizing, as well as pain and opioid use history, predicted greater difficulty with pain management among hospitalized cancer patients, suggesting that early assessment of patient-level characteristics may help direct consultation for more intensive pharmacologic and nonpharmacologic interventions.

The Relationship of Postoperative Pain and Opioid Consumption to Postoperative Delirium After Spine Surgery.

Purpose: To examine the relationship between postoperative pain and opioid use and the development of postoperative delirium (POD), with attention to the preoperative opioid use status of patients. Methods: This was a secondary analysis of data from a prospective observational study of patients (N = 219; ≥70 years old) scheduled to undergo elective spine surgery. Maximal daily pain scores (0-10) and postoperative morphine milligram equivalents per hour (MME/hr) were determined for postoperative days 1-3 (D1-3). POD was assessed by daily in-person interviews using the Confusion Assessment Method and chart review. Results: Patients who reported regular preoperative opioid use (n = 58, 27%) reported significantly greater maximal daily pain scores, despite also requiring greater daily opioids (MME/hr) in the first 3 days after surgery. These patients were also more likely to develop POD. Interestingly, while postoperative pain scores were significantly higher in patients who developed POD, postoperative opioid consumption was not significantly higher in this group. Conclusion: POD was associated with greater postoperative pain, but not with postoperative opioid consumption. While postoperative opioid consumption is often blamed for delirium, these findings suggest that uncontrolled pain may actually be a more important factor, particularly among patients who are opioid tolerant. These findings underscore the importance of employing multimodal perioperative analgesic management, especially among older patients who have a predilection to developing POD and baseline tolerance to opioids.

Brief Mindfulness-Based Cognitive Behavioral Therapy is Associated with Faster Recovery in Patients Undergoing Total Knee Arthroplasty: A Pilot Clinical Trial.

OBJECTIVE: To assess whether brief mindfulness-based cognitive behavioral therapy (MBCBT) could enhance the benefits of total knee arthroplasty (TKA) in improving pain and pain-related disability. Specifically, to determine 1) whether patients who received MBCBT differed from matched controls who received treatment-as-usual with regard to postsurgical pain outcomes and 2) whether changes in pain catastrophizing, depression, or anxiety explained the potential effects of MBCBT on pain outcomes. DESIGN: Pilot clinical trial. SETTING: An academic teaching hospital serving a large urban and suburban catchment area surrounding the Boston, Massachusetts metropolitan region. SUBJECTS: Sample of 44 patients undergoing TKA. Patients who completed a brief MBCBT intervention (n = 22) were compared with age-, race-, and sex-matched controls who received treatment-as-usual (n = 22). METHODS: The MBCBT intervention included four 60-minute sessions delivered by a pain psychologist in person and via telephone during the perioperative period. Participants were assessed at baseline and at 6 weeks, 3 months, and 6 months after surgery. RESULTS: Compared with matched controls, patients who received MBCBT had lower pain severity and pain interference at 6 weeks after surgery. Group differences in outcomes were mediated by changes in pain catastrophizing but not by changes in depression or anxiety. The MBCBT group had similar reductions in pain severity and interference as the control group did at 3 and 6 months after surgery. CONCLUSIONS: This work offers evidence for a safe and flexibly delivered nonpharmacological treatment (MBCBT) to promote faster recovery from TKA and identifies change in pain catastrophizing as a mechanism by which this intervention could lead to enhanced pain-related outcomes.

Early postoperative psychological distress as a mediator of subsequent persistent postsurgical pain outcomes among younger breast cancer patients.

PURPOSE: Younger age is a risk factor for worse pain outcomes following breast cancer surgery, yet little is known about how younger women's psychological state may contribute to their pain experience. Using prospectively collected longitudinal data from a surgical cohort, we examined whether early postoperative psychological distress at 2 weeks mediated the association between younger age and subsequent worse pain-related functioning 3 months after surgery. METHODS: Patients (N = 159) were recruited before breast cancer surgery into this longitudinal cohort study. Age at time of surgery, psychological distress (anxiety, depression, and sleep disturbance) assessed 2 weeks postoperatively, and impact of surgical pain on cognitive/emotional functioning and physical functioning assessed 3 months postoperatively were used for analysis. RESULTS: Younger age was associated with greater depression, anxiety, and sleep disturbance 2 weeks postoperatively. Younger age was also associated with greater ratings of pain impacting cognitive/emotional functioning and physical functioning 3 months postoperatively. The association between younger age and worse cognitive/emotional impact of pain was mediated by greater anxiety and sleep disturbance. Similarly, the association between younger age and worse physical impact of pain was mediated by greater sleep disturbance. CONCLUSION: The degree of anxiety and sleep disturbance that occur early after breast surgery may contribute to greater chronic pain-related functional disability among younger patients. Anxiety and sleep disturbance are modifiable with behavioral interventions, making them potential perioperative targets to improve long-term outcomes in young breast cancer survivors.

Applying the Rapid OPPERA Algorithm to Predict Persistent Pain Outcomes Among a Cohort of Women Undergoing Breast Cancer Surgery.

Persistent postmastectomy pain after breast surgery is variable in duration and severity across patients, due in part to interindividual variability in pain processing. The Rapid OPPERA Algorithm (ROPA) empirically identified 3 clusters of patients with different risk of chronic pain based on 4 key psychophysical and psychosocial characteristics. We aimed to test this type of group-based clustering within in a perioperative cohort undergoing breast surgery to investigate differences in postsurgical pain outcomes. Women (N = 228) scheduled for breast cancer surgery were prospectively enrolled in a longitudinal observational study. Pressure pain threshold (PPT), anxiety, depression, and somatization were assessed preoperatively. At 2-weeks, 3, 6, and 12-months after surgery, patients reported surgical area pain severity, impact of pain on cognitive/emotional and physical functioning, and pain catastrophizing. The ROPA clustering, which used patients' preoperative anxiety, depression, somatization, and PPT scores, assigned patients to 3 groups: Adaptive (low psychosocial scores, high PPT), Pain Sensitive (moderate psychosocial scores, low PPT), and Global Symptoms (high psychosocial scores, moderate PPT). The Global Symptoms cluster, compared to other clusters, reported significantly worse persistent pain outcomes following surgery. Findings suggest that patient characteristic-based clustering algorithms, like ROPA, may generalize across diverse diagnoses and clinical settings, indicating the importance of "person type" in understanding pain variability. PERSPECTIVE: This article presents the practical translation of a previously developed patient clustering solution, based within a chronic pain cohort, to a perioperative cohort of women undergoing breast cancer surgery. Such preoperative characterization could potentially help clinicians apply personalized interventions based on predictions concerning postsurgical pain.

Psychological Evaluation of Patients With Cancer Presenting to the Emergency Department With Pain: Independent Predictors of Worse Pain Severity, Interference, and Higher Hourly Opioid Administration.

PURPOSE: Pain is a common complaint in patients with cancer presenting to the emergency department (ED). This prospective study evaluated whether biopsychosocial factors could help predict cancer patients with risk of higher pain severity, pain interference, and opioid consumption. METHODS: Patients with cancer presenting to the ED with a complaint of moderate-severe pain (≥ 4/10-numeric rating scale) completed validated self-report measures assessing sociodemographics, cancer-related treatments, pain severity and interference, medication use, and psychological symptoms (depression, anxiety, pain catastrophizing, and sleep disturbance). Opioids administered and subsequent hospitalization were abstracted. Univariable and multivariable regression analyses assessed factors associated with pain-related outcomes. RESULTS: Participants (n = 175) presented with a variety of cancer types, with 76% having metastatic disease and 42% reporting current outpatient opioid use. Higher pain catastrophizing, lower depressive symptoms, lower income, outpatient opioid use, and historical chronic pain were independently associated with worse pain (P ≤ .05). Higher pain catastrophizing, anxiety, sleep disturbance, outpatient opioid use, and education were independently associated with worse pain interference (P ≤ .05). The sole independent predictor of ED opioid administration was outpatient opioid use. Patients taking outpatient opioids were younger, had lower health literacy, worse pain catastrophizing, sleep disturbance, depression/anxiety, and greater rates of metastatic cancer and cancer-related surgery (P ≤ .05). CONCLUSION: Biopsychosocial factors, particularly pain catastrophizing, remained significantly associated with worse pain outcomes for patients with cancer in the ED even after controlling for demographic and clinical variables. Patient outpatient opioid use was independently associated with worse pain, interference, and greater opioid administration, identifying this as a marker for who may benefit most from adjuvant pharmacologic and behavioral interventions.

Increased pain catastrophizing longitudinally predicts worsened pain severity and interference in patients with chronic pain and cancer: A collaborative health outcomes information registry study (CHOIR).

OBJECTIVE: Little is known about how changes in psychosocial factors impact changes in pain outcomes among patients with cancer and chronic pain. This longitudinal cohort study of cancer patients investigated the relationships between changes in psychosocial factors and changes in pain severity and interference over time. METHODS: Data from patients with cancer and chronic pain (n = 316) treated at a tertiary pain clinic were prospectively collected. At their baseline visit (Time 1), patients provided demographic and clinical information, and completed validated psychosocial and pain assessments. Psychosocial and pain assessments were repeated at a follow-up visit (Time 2), on average 4.9 months later. Change scores (Time 2-Time 1) were computed for psychosocial and pain variables. Multivariable hierarchical linear regressions assessed the associations between changes in psychosocial factors with changes in pain outcomes over time. RESULTS: Participants were an average age of 59 years, were 61% female, and 69% White. Overall, a decrease in pain severity (p ≤ 0.001), but not pain interference, was observed among the group over time. In multivariable analyses, increased pain catastrophizing was significantly associated with increased pain severity over time (ß = 0.24, p ≤ 0.001). Similarly, increased pain catastrophizing (ß = 0.21, p ≤ 0.001) and increased depression (ß = 0.20, p ≤ 0.003) were significantly associated with increased pain interference over time. Demographic and clinical characteristics were not significantly related to changes in pain outcomes. CONCLUSIONS: Increased pain catastrophizing was uniquely associated with increased chronic pain severity and interference. Our findings indicate that cancer patients with chronic pain would likely benefit from the incorporation of nonpharmacological interventions, simultaneously addressing pain and psychological symptoms.

Impact of varying degrees of peripheral nerve blockade on experimental pressure and ischemic pain: adductor canal and sciatic nerve blocks in a human model of compartment syndrome pain.

INTRODUCTION: Early diagnosis of acute extremity compartment syndrome is crucial to timely surgical management. Pain is commonly used as an early diagnostic sign for acute extremity compartment syndrome, making regional anesthesia after lower extremity surgery controversial. This randomized study tested whether different concentrations of local anesthetics, or combinations of nerve blocks, would differentially impact the perception of acute extremity compartment syndrome-like pressure and ischemic pain. METHODS: Healthy volunteers underwent quantitative sensory testing, including determination of pressure pain thresholds and prolonged pressure/ischemic pain in the leg using a variable cuff inflation system. Subjects were randomized to receive (1) adductor canal block alone (ACB), (2) ACB with low-concentration sciatic nerve block (ACB +LC SNB), or (3) ACB with high-concentration SNB (ACB +HC SNB). For the primary outcome, we assessed block-induced increases in pressure threshold to reach 6/10 pain, and compared the degree of increase between the three groups. The main secondary outcome was a comparison of average pain score during a 5 min hold at the 6/10 pressure pain threshold between the three groups. RESULTS: All blocks raised pressure pain threshold and decreased ischemic pain, but to variable extents. Specifically, the amount the block increased pressure pain threshold was significantly different among ACB, ACB+LC SNB, and ACB+HC SNB groups (mean±SD: 24±32 mm Hg, 120±103 mm Hg, 159±93 mm Hg; p=0.002), with post hoc testing revealing ACB as less than the other two groups. Similarly, average pain scores during a prolonged/ischemic cuff hold differed among the groups (4.2±1.4, 1.4±1.7, 0.4±0.7; p<0.001), with post hoc testing revealing ACB as significantly higher. DISCUSSION: This study suggests the possible utility of titrating regional anesthesia, to provide some analgesia while still allowing acute extremity compartment syndrome detection. TRIAL REGISTRATION NUMBER: NCT04113954.