Hypoalgesia and Conditioned Pain Modulation in Blood Flow Restriction Resistance Exercise.

We compared the magnitude of exercise-induced hypoalgesia and conditioned pain modulation between blood-flow restriction (BFR) resistance exercise (RE) and moderate-intensity RE. Twenty-five asymptomatic participants performed unilateral leg press in two visits. For moderate-intensity RE, subjects exercised at 50% 1RM without BFR whereas BFR RE exercised at 30% 1RM with a cuff inflated to 60% limb occlusion pressure. Exercise-induced hypoalgesia was quantified by pressure pain threshold changes before and after RE. Conditioned pain modulation was tested using cold water as the conditioning stimulus and mechanical pressure as the test stimulus and quantified as pressure pain threshold change. Difference in conditioned pain modulation pre- to post- RE was then calculated. The differences of RE on pain modulations were compared using paired t-tests. Pearson's r was used to examine the correlation between exercise-induced hypoalgesia and changes in conditioned pain modulation. We found greater hypoalgesia with BFR RE compared to moderate-intensity RE (p = 0.008). Significant moderate correlations were found between exercise-induced hypoalgesia and changes in conditioned pain modulation (BFR: r = 0.63, moderate-intensity: r = 0.72). BFR RE has favorable effects on pain modulation in healthy adults and the magnitude of exercise-induced hypoalgesia is positively correlated with conditioned pain modulation activation.

Translating Outcomes from the Clinical Setting to Preclinical Models: Chronic Pain and Functionality in Chronic Musculoskeletal Pain.

Fibromyalgia (FM) is a chronic pain disorder characterized by chronic widespread musculoskeletal pain (CWP), resting pain, movement-evoked pain (MEP), and other somatic symptoms that interfere with daily functioning and quality of life. In clinical studies, this symptomology is assessed, while preclinical models of CWP are limited to nociceptive assays. The aim of the study was to investigate the human-to-model translatability of clinical behavioral assessments for spontaneous (or resting) pain and MEP in a preclinical model of CWP. For preclinical measures, the acidic saline model of FM was used to induce widespread muscle pain in adult female mice. Two intramuscular injections of acidic or neutral pH saline were administered following baseline measures, 5 days apart. An array of adapted evoked and spontaneous pain measures and functional assays were assessed for 3 weeks. A novel paradigm for MEP assessment showed increased spontaneous pain following activity. For clinical measures, resting and movement-evoked pain and function were assessed in adult women with FM. Moreover, we assessed correlations between the preclinical model of CWP and in women with fibromyalgia to examine whether similar relationships between pain assays that comprise resting and MEP existed in both settings. For both preclinical and clinical outcomes, MEP was significantly associated with mechanical pain sensitivity. Preclinically, it is imperative to expand how the field assesses spontaneous pain and MEP when studying multi-symptom disorders like FM. Targeted pain assessments to match those performed clinically is an important aspect of improving preclinical to clinical translatability of animal models.

Racial and weight discrimination associations with pain intensity and pain interference in an ethnically diverse sample of adults with obesity: a baseline analysis of the clustered randomized-controlled clinical trial the goals for eating and moving (GEM) study.

BACKGROUND: Everyday experiences with racial (RD) and weight discrimination (WD) are risk factors for chronic pain in ethnically diverse adults with obesity. However, the individual or combined effects of RD and WD on pain in adults with obesity is not well understood. There are gender differences and sexual dimorphisms in nociception and pain, but the effect of gender on relationships between RD, WD, and pain outcomes in ethnically diverse adults with obesity is unclear. Thus, the purposes of this study were to: 1) examine whether RD and WD are associated with pain intensity and interference, and 2) explore gender as a moderator of the associations between RD, WD, and pain. METHODS: This is a baseline data analysis from a randomized, controlled clinical trial of a lifestyle weight-management intervention. Eligible participants were English or Spanish-speaking (ages 18-69 years) and had either a body mass index of ≥30 kg/m2 or ≥ 25 kg/m2 with weight-related comorbidity. RD and WD were measured using questions derived from the Experiences of Discrimination questionnaire (EOD). Pain interference and intensity were measured using the PROMIS 29 adult profile V2.1. Linear regression models were performed to determine the associations between WD, RD, gender, and pain outcomes. RESULTS: Participants (n = 483) reported mild pain interference (T-score: 52.65 ± 10.29) and moderate pain intensity (4.23 ± 3.15). RD was more strongly associated with pain interference in women (b = .47, SE = .08, p < 001), compared to men (b = .14, SE = .07, p = .06). Also, there were no significant interaction effects between RD and gender on pain intensity, or between WD and gender on pain interference or pain intensity. CONCLUSIONS: Pain is highly prevalent in adults with obesity, and is impacted by the frequencies of experiences with RD and WD. Further, discrimination against adults with obesity and chronic pain could exacerbate existing racial disparities in pain and weight management. Asking ethnically diverse adults with obesity about their pain and their experiences of RD and WD could help clinicians make culturally informed assessment and intervention decisions that address barriers to pain relief and weight loss. TRIAL REGISTRATION: NCT03006328.

Reliability and Construct Validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) Instruments in Women with Fibromyalgia.

OBJECTIVE: The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to standardize measurement of clinically relevant patient-reported outcomes. This study evaluated the reliability and construct validity of select PROMIS static short-form (SF) instruments in women with fibromyalgia. DESIGN: Analysis of baseline data from the Fibromyalgia Activity Study with TENS (FAST), a randomized controlled trial of the efficacy of transcutaneous electrical nerve stimulation. SETTING: Dual site, university-based outpatient clinics. SUBJECTS: Women aged 20 to 67 years diagnosed with fibromyalgia. METHODS: Participants completed the Revised Fibromyalgia Impact Questionnaire (FIQR) and 10 PROMIS static SF instruments. Internal consistency was calculated using Cronbach alpha. Convergent validity was examined against the FIQR using Pearson correlation and multiple regression analysis. RESULTS: PROMIS static SF instruments had fair to high internal consistency (Cronbach α = 0.58 to 0.94, P < 0.05). PROMIS 'physical function' domain score was highly correlated with FIQR 'function' score (r = -0.73). The PROMIS 'total' score was highly correlated with the FIQR total score (r = -0.72). Correlations with FIQR total score of each of the three PROMIS domain scores were r = -0.65 for 'physical function,' r = -0.63 for 'global,' and r = -0.57 for 'symptom' domain. PROMIS 'physical function,' 'global,' and 'symptom' scores explained 58% of the FIQR total score variance. CONCLUSIONS: Select PROMIS static SF instruments demonstrate convergent validity with the FIQR, a legacy measure of fibromyalgia disease severity. These results highlight the potential utility of select PROMIS static SFs for assessment and tracking of patient-reported outcomes in fibromyalgia.

Influence of Transcutaneous Electrical Nerve Stimulation (TENS) on Pressure Pain Thresholds and Conditioned Pain Modulation in a Randomized Controlled Trial in Women With Fibromyalgia.

Transcutaneous electrical nerve stimulation (TENS) effectively reduces pain in fibromyalgia (FM). The purpose of this study was to examine the influence of TENS use on pressure pain thresholds (PPT) and conditioned pain modulation (CPM) in individuals with FM using data from the Fibromyalgia Activity Study with TENS trial (NCT01888640). Individuals with FM were randomly assigned to receive active TENS, placebo TENS, or no TENS for 4 weeks. A total of 238 females satisfied the per-protocol analysis among the active TENS (n = 76), placebo TENS (n = 68), and no TENS (n = 94) groups. Following 4 weeks of group allocation, the active TENS group continued for an additional 4 weeks of active TENS totaling 8 weeks (n = 66), the placebo and no TENS groups transitioned to receive 4 weeks of active TENS (delayed TENS, n = 161). Assessment of resting pain, movement-evoked pain (MEP), PPT, and CPM occurred prior to and following active, placebo, or no TENS. There were no significant changes in PPT or CPM among the active TENS, placebo TENS, or no TENS groups after 4 weeks. Individuals who reported clinically relevant improvements in MEP (≥30% decrease) demonstrated increases in PPT (P < .001), but not CPM, when compared to MEP non-responders. There were no significant correlations among the change in PPT or CPM compared to MEP and resting pain following active TENS use (active TENS + delayed TENS). PPT and CPM may provide insight to underlying mechanisms contributing to pain; however, these measures may not relate to self-reported pain symptoms. PERSPECTIVE: Pressure pain threshold increased in individuals with clinically relevant improvement (≥30%) in MEP, indicating the clinical relevance of PPT for understanding mechanisms contributing to pain. CPM was not a reliable indicator of treatment response in MEP responders.

Through the Lens of Movement-Evoked Pain: A Theoretical Framework of the "Pain-Movement Interface" to Guide Research and Clinical Care for Musculoskeletal Pain Conditions.

Over 120 million Americans report experiencing pain in the past 3 months. Among these individuals, 50 million report chronic pain and 17 million report pain that limits daily life or work activities on most days (ie, high-impact chronic pain). Musculoskeletal pain conditions in particular are a major contributor to global disability, health care costs, and poor quality of life. Movement-evoked pain (MEP) is an important and distinct component of the musculoskeletal pain experience and represents an emerging area of study in pain and rehabilitation fields. This focus article proposes the "Pain-Movement Interface" as a theoretical framework of MEP that highlights the interface between MEP, pain interference, and activity engagement. The goal of the framework is to expand knowledge about MEP by guiding scientific inquiry into MEP-specific pathways to disability, high-risk clinical phenotypes, and underlying individual influences that may serve as treatment targets. This framework reinforces the dynamic nature of MEP within the context of activity engagement, participation in life and social roles, and the broader pain experience. Recommendations for MEP evaluation, encompassing the spectrum from high standardization to high patient specificity, and MEP-targeted treatments are provided. Overall, the proposed framework and recommendations reflect the current state of science in this emerging area of study and are intended to support future efforts to optimize musculoskeletal pain management and enhance patient outcomes. PERSPECTIVE: Movement-evoked pain (MEP) is a distinct component of the musculoskeletal pain experience and emerging research area. This article introduces the "Pain-Movement Interface" as a theoretical framework of MEP, highlighting the interface between MEP, pain interference, and activity engagement. Evaluating and treating MEP could improve rehabilitation approaches and enhance patient outcomes.

Racism exposure and trauma accumulation perpetuate pain inequities-advocating for change (RESTORATIVE): A conceptual model.

Experiences of racism occur across a continuum from denial of services to more subtle forms of discrimination and exact a significant toll. These multilevel systems of oppression accumulate as chronic stressors that cause psychological injury conceptualized as racism-based traumatic stress (RBTS). RBTS has overlapping symptoms with posttraumatic stress disorder (PTSD) with the added burden that threats are constantly present. Chronic pain is a public health crisis that is exacerbated by the intersection of racism and health inequities. However, the relationship between RBTS and pain has not yet been explored. To highlight how these phenomena are interlinked, we present Racism ExpoSure and Trauma AccumulatiOn PeRpetuate PAin InequiTIes-AdVocating for ChangE (RESTORATIVE); a novel conceptual model that integrates the models of racism and pain and demonstrates how the shared contribution of trauma symptoms (e.g., RBTS and PTSD) maintains and perpetuates chronic pain for racialized groups in the United States. Visualizing racism and pain as "two halves of the same coin," in which the accumulative effects of numerous events may moderate the severity of RBTS and pain, we emphasize the importance of within-group distinctiveness and intersectionality (overlapping identities). We call on psychologists to lead efforts in applying the RESTORATIVE model, acting as facilitators and advocates for the patient's lived experience with RBTS in clinical pain care teams. To assist with this goal, we offer suggestions for provider and researcher antiracism education, assessment of RBTS in pain populations, and discuss how cultural humility is a central component in implementing the RESTORATIVE model. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Confronting Racism in All Forms of Pain Research: Reframing Study Designs.

This second paper in a 3-part series on antiracism in pain research across the translational spectrum focuses on study design factors. Although objectivity is a cornerstone value of science, subjectivity is embedded in every step of the research process as investigators make choices about who they collaborate with, which research questions they ask, how they recruit participants, which research tools they use, and how they analyze and interpret data. We present theory and evidence from disciplines such as sociology, medical anthropology, statistics, and public health to discuss 4 common study design factors, including 1) the dominant biomedical narrative of pain that restricts funding and exploration of social indicators of pain, 2) low diversity and inclusion in pain research enrollment that restricts generalizability to racialized groups, 3) the use of "race" or "ethnicity" as a statistical variable and proxy for lived experiences (eg, racism, resilience), and 4) limited modeling in preclinical research for the impact of social factors on pain physiology. The information presented in this article is intended to start conversations across stakeholders in the pain field to explore how we can come together to adopt antiracism practices in our work at large to achieve equity for racialized groups. PERSPECTIVE: This is the second paper in a 3-part series on antiracism in pain research. This part identifies common study design factors that risk hindering progress toward pain care equity. We suggest reframes using an antiracism framework for these factors to encourage all pain investigators to collectively make strides toward equity.

Confronting Racism in Pain Research: A Call to Action.

Racism is an established health determinant across the world. In this 3-part series, we argue that a disregard of how racism manifests in pain research practices perpetuates pain inequities and slows the progression of the field. Our goal in part-1 is to provide a historical and theoretical background of racism as a foundation for understanding how an antiracism pain research framework - which focuses on the impact of racism, rather than "race," on pain outcomes - can be incorporated across the continuum of pain research. We also describe cultural humility as a lifelong self-awareness process critical to ending generalizations and successfully applying antiracism research practices through the pain research continuum. In part-2 of the series, we describe research designs that perpetuate racism and provide reframes. Finally, in part-3, we emphasize the implications of an antiracism framework for research dissemination, community-engagement practices and diversity in research teams. Through this series, we invite the pain research community to share our commitment to the active process of antiracism, which involves both self-examination and re-evaluation of research practices shifting our collective work towards eliminating racialized injustices in our approach to pain research. PERSPECTIVE: We call on the pain community to dismantle racism in our research practices. As the first paper of the 3-part series, we introduce dimensions of racism and its effect on pain inequities. We also describe the imperative role of cultural humility in adopting antiracism pain research practices.

Confronting Racism in All Forms of Pain Research: A Shared Commitment for Engagement, Diversity, and Dissemination.

This third paper in the "Confronting Racism in All Forms of Pain Research" series discusses adopting an antiracism framework across all pain research disciplines and highlights the significant benefits of doing so. We build upon the previous call to action and the proposed reframing of study designs articulated in the other papers in the series and seek to confront and eradicate racism through a shared commitment to change current research practices. Specifically, we emphasize the systematic disadvantage created by racialization (ie, the Eurocentric social and political process of ascribing racialized identities to a relationship, social practice, or group) and discuss how engaging communities in partnership can increase the participation of racialized groups in research studies and enrich the knowledge gained. Alongside this critical work, we indicate why diversifying the research environment (ie, research teams, labs, departments, and culture) enriches our scientific discovery and promotes recruitment and retention of participants from racialized groups. Finally, we recommend changes in reporting and dissemination practices so that we do not stigmatize or reproduce oppressive forms of power for racialized groups. Although this shift may be challenging in some cases, the increase in equity, generalizability, and credibility of the data produced will expand our knowledge and reflect the pain experiences of all communities more accurately. PERSPECTIVE: In this third paper in our series, we advocate for a shared commitment toward an antiracism framework in pain research. We identify community partnerships, diversification of research environments, and changes to our dissemination practices as areas where oppressive forms of power can be reduced.

Toward Understanding Movement-evoked Pain (MEP) and its Measurement: A Scoping Review.

OBJECTIVE: Individuals with chronic pain conditions often report movement as exacerbating pain. An increasing number of researchers and clinicians have recognized the importance of measuring and distinguishing between movement-evoked pain (MEP) and pain at rest as an outcome. This scoping review maps the literature and describes MEP measurement techniques. MATERIALS AND METHODS: The scoping review utilized 6 databases to identify original studies that targeted pain or movement-related outcomes. Our search returned 7322 articles that were screened by title and abstract by 2 reviewers. The inclusion criteria focused on the measurement of MEP before, during, and after movement tasks in adults with chronic pain. Studies of children below 18 years of age or with nonhuman animals, case studies, qualitative studies, book chapters, cancer-related pain, non-English language, and abstracts with no full publish text were excluded from the study. RESULTS: Results from 38 studies revealed great variation in the measurement of MEP, while almost all of the studies did not provide an explicit conceptual or operational definition for MEP. In addition, studies collectively illuminated differences in MEP compared with rest pain, movement provocation methods, and pain intensity as the primary outcome. DISCUSSION: These results have clinically significant and research implications. To advance the study of MEP, we offer that consistent terminology, standardized measurement (appropriate for pain type/population), and clear methodological processes be provided in research publications. On the basis of the findings, we have put forth a preliminary definition of MEP that may benefit from the continued scholarly dialog.

IL-5 mediates monocyte phenotype and pain outcomes in fibromyalgia.

ABSTRACT: Fibromyalgia (FM) is characterized by widespread chronic pain, fatigue, and somatic symptoms. The influence of phenotypic changes in monocytes on symptoms associated with FM is not fully understood. The primary aim of this study was to take a comprehensive whole-body to molecular approach in characterizing relationships between monocyte phenotype and FM symptoms in relevant clinical populations. Lipopolysaccharide-evoked and spontaneous secretion of IL-5 and other select cytokines from circulating monocytes was higher in women with FM compared to women without pain. In addition, greater secretion of IL-5 was significantly associated with pain and other clinically relevant psychological and somatic symptoms of FM. Furthermore, higher levels of pain and pain-related symptoms were associated with a lower percentage of intermediate monocytes (CD14++/CD16+) and a greater percentage of nonclassical monocytes (CD14+/CD16++) in women with FM. Based on findings from individuals with FM, we examined the role of IL-5, an atypical cytokine secreted from monocytes, in an animal model of widespread muscle pain. Results from the animal model show that IL-5 produces analgesia and polarizes monocytes toward an anti-inflammatory phenotype (CD206+). Taken together, our data suggest that monocyte phenotype and their cytokine profiles are associated with pain-related symptoms in individuals with FM. Furthermore, our data show that IL-5 has a potential role in analgesia in an animal model of FM. Thus, targeting anti-inflammatory cytokines such as IL-5 secreted by circulating leukocytes could serve as a promising intervention to control pain and other somatic symptoms associated with FM.

Local Anesthetic Injection Resolves Movement Pain, Motor Dysfunction, and Pain Catastrophizing in Individuals With Chronic Achilles Tendinopathy: A Nonrandomized Clinical Trial.

OBJECTIVES: Peripherally directed treatments (targeted exercise, surgery) can reduce, but not fully eliminate, pain for up to 40% of patients with Achilles tendinopathy. The objectives of the present study were (1) to identify indicators of altered central processing in participants with Achilles tendinopathy compared to controls, and (2) to determine which indicators of altered central processing would persist after a local anesthetic injection in patients with Achilles tendinopathy. DESIGN: Mechanistic clinical trial. METHODS: Forty-six adults (23 with chronic Achilles tendinopathy, 23 matched controls) repeated (1) a movement-evoked pain rating, (2) motor performance assessment, (3) pain psychology questionnaires, and (4) quantitative sensory testing. Participants with Achilles tendinopathy received a local anesthetic injection before repeat testing and controls did not. Mixed-effects analyses of variance examined the effects of group, time, and group by time. RESULTS: The Achilles tendinopathy group had movement-evoked pain, motor dysfunction, and higher pain psychological factors (pain catastrophizing, kinesiophobia) compared to controls (P<.05). The Achilles tendinopathy group did not have indicators of nociplastic pain with quantitative sensory testing (P>.05). In those with Achilles tendinopathy, local anesthetic injection eliminated pain and normalized the observed deficits in heel-raise performance and pain catastrophizing (group-by-time effect, P<.01), but not in kinesiophobia (P = .45). Injection did not affect measures of nociplastic pain (P>.05). CONCLUSION: People with Achilles tendinopathy had elevated pain psychological factors and motor dysfunction but no signs of nociplastic pain with quantitative sensory testing. Removal of nociceptive input normalized movement-evoked pain and some indicators of altered central processing (motor dysfunction, pain catastrophizing), but not kinesiophobia. J Orthop Sports Phys Ther 2020;50(6):334-343. Epub 29 Apr 2020. doi:10.2519/jospt.2020.9242.

Somatic symptom presentations in women with fibromyalgia are differentially associated with elevated depression and anxiety.

This study examined whether depression and anxiety differentially relate to fatigue, sleep disturbance, pain catastrophizing, fear of movement, and pain severity in women with fibromyalgia. Baseline data from the Fibromyalgia Activity Study with Transcutaneous Electrical Nerve Stimulation were analyzed. Of 191 participants, 50 percent reported high anxiety and/or depression (17% high anxiety, 9% high depression, and 24% both). Fatigue and sleep impairment were associated with high depression (p < 0.05). Pain severity, pain catastrophizing, and fear of movement were associated with high anxiety and high depression (p < 0.05). Possible implications for underlying mechanisms and the need for targeted treatments are discussed.

Transcutaneous Electrical Nerve Stimulation Reduces Movement-Evoked Pain and Fatigue: A Randomized, Controlled Trial.

OBJECTIVE: Fibromyalgia (FM) is characterized by pain and fatigue, particularly during physical activity. Transcutaneous electrical nerve stimulation (TENS) activates endogenous pain inhibitory mechanisms. This study was undertaken to investigate if using TENS during activity would improve movement-evoked pain and other patient-reported outcomes in women with FM. METHODS: Participants were randomly assigned to receive active TENS (n = 103), placebo TENS (n = 99), or no TENS (n = 99) and instructed to use it at home during activity 2 hours each day for 4 weeks. TENS was applied to the lumbar and cervicothoracic regions using a modulated frequency (2-125 Hz) at the highest tolerable intensity. Participants rated movement-evoked pain (primary outcome measure) and fatigue on an 11-point scale before and during application of TENS. The primary outcome measure and secondary patient-reported outcomes were assessed at baseline (time of randomization) and at 4 weeks. RESULTS: After 4 weeks, a greater reduction in movement-evoked pain was reported in the active TENS group versus the placebo TENS group (group mean difference -1.0 [95% confidence interval -1.8, -0.2]; P = 0.008) and versus the no TENS group (group mean difference -1.8 [95% confidence interval -2.6, -1.0]; P < 0.0001). A reduction in movement-evoked fatigue was also reported in the active TENS group versus the placebo TENS group (group mean difference -1.4 [95% confidence interval -2.4, -0.4]; P = 0.001) and versus the no TENS group (group mean difference -1.9 [95% confidence interval -2.9, -0.9]; P = <0.0001). A greater percentage of the patients in the active TENS group reported improvement on the global impression of change compared to the placebo TENS group (70% versus 31%; P < 0.0001) and the no TENS group (9%; P < 0.0001). There were no TENS-related serious adverse events, and <5% of participants experienced minor adverse events from TENS. CONCLUSION: Among women who had FM and were on a stable medication regimen, 4 weeks of active TENS use compared to placebo TENS or no TENS resulted in a significant improvement in movement-evoked pain and other clinical outcomes. Further research is needed to examine effectiveness in a real-world setting to establish the clinical importance of these findings.

Minimum detectable change in gait velocity during acute rehabilitation following hip fracture.

PURPOSE: Early ambulation and rehabilitation are recommended for patients undergoing surgical fixation of hip fracture. Gait velocity may be used as an outcome measure for these patients during acute rehabilitation. As an outcome measure, an estimate of meaningful change (responsiveness) in gait velocity for these patients, however, has not been described. The minimum detectable change (MDC) is a value that represents true change in a measure beyond that accounted for by measurement error. The purpose of this study was to quantify MDC in gait velocity as an index of responsiveness for persons in the acute stage of rehabilitation following hip fracture. METHODS: The study design was a descriptive cohort study with one repeated measure. A volunteer sample of 16 subjects over the age of 65, at a mean of 4.7 days postsurgical fixation of unilateral hip fracture, participated in the study. The study was conducted in an acute care rehabilitation practice in a large, tertiary care hospital. We measured gait velocity with the 10-meter walk test, estimated test-retest reliability with an intraclass correlation coefficient and quantified responsiveness of gait velocity as the MDC at a 95% level of confidence. RESULTS: Mean gait velocity was 15 cm/s and the test-retest reliability coefficient was equal to 0.823. The MDC in gait velocity during acute rehabilitation following surgical repair for hip fracture was 8.2 cm/s. CONCLUSIONS: Self-selected gait velocity in patients during acute rehabilitation following surgical fixation for hip fracture must improve by 8.2 cm/s or more to designate the change as being real change beyond the bounds of measurement error.