Human Studies

Among 170 adults with sickle cell disease, we evaluated chronic pain impact and disability prevalence, assessed age and gender differences, and identified psychosocial predictors of chronic pain intensity and disability. Most participants had a high level of disability. Chronic pain intensity and disability were significantly associated with pain catastrophizing and chronic pain self-efficacy, and worsened with age. Further research is needed to confirm study findings and develop interventions, including palliative care approaches that address catastrophizing and disability, particularly for young women and middle-aged adults with sickle cell disease. Moreover, consistent clinical assessment of chronic pain and psychosocial health should be implemented.

Current guidelines for addressing opioid cessation in the context of chronic pain management recommend that opioids be discontinued if the risks outweigh the benefits. However, few studies have focused on understanding opioid cessation from the perspective of individuals with chronic pain. This mixed-method study included 49 former opioid users with chronic pain and used quantitative survey data and qualitative focus group data to identify themes pertaining to former opioid user's experience before, during, and after opioid cessation. Participants described several reasons for wanting to stop opioids including lack of efficacy, impact on quality of life, and concerns about addiction. Barriers to cessation included concerns about inadequate pain management and concerns about the impact of stopping opioids on mood. After opioid cessation, the sample was mixed regarding the benefit of cessation. Half of the former opioid users reported their pain to be better or the same after stopping opioids; however, 47% of the sample reported feeling worse pain since stopping their opioids. As the pendulum swings from pain control to drug control, we must ensure that the response to the opioid epidemic does not cause harm to individuals with chronic pain. Novel opioid cessation interventions are needed in combination with methods of addressing individual challenges and barriers to adequate pain relief including access to and provision of nonopioid alternatives for pain management.

Childhood trauma has been linked to neuropathic pain in noncancer populations, but its relationship with cancer treatment-related neuropathic pain is unknown.

This study examined psychosocial pain treatment moderation in a secondary analysis of a trial that compared cognitive therapy (CT), mindfulness-meditation (MM), and mindfulness-based cognitive therapy (MBCT) for chronic low back pain (CLBP). The Limit, Activate and Enhance (LA&E) model of moderation provided a framework for testing a priori hypotheses. Adult participants (N=69) with CLBP completed a pre-treatment assessment of hypothesized moderators: pain catastrophizing, brain state as assessed by electroencephalogram, mindful observing, and non-reactivity. Outcomes were pain interference, characteristic pain intensity, physical function, and depression, assessed at pre- and post-treatment. Moderation analyses found significant interaction effects, specifically: (1) higher and lower baseline pain catastrophizing was associated with greater improvement in pain intensity in MM and MBCT, respectively; (2) higher baseline theta power was associated with greater improvement in depression in MBCT and interfered with response to CT; (3) lower baseline non-reactivity was associated with greater improvement in physical function in MM while higher non-reactivity was associated with greater improvement in MBCT. The findings support the possibility that different patients are more or less likely to benefit from various treatments. Theory-driven moderation research has the capacity to inform the development of patient-treatment matching algorithms to optimize outcome. Perspective: This study presents preliminary findings from theory-driven tests of the moderators of mindfulness meditation, cognitive therapy and mindfulness-based cognitive therapy for chronic low back pain. The results of such analyses may inform the understanding of for whom various evidence-based psychosocial pain treatments may engender the most meaningful benefits.

Chronic low back pain (CLBP) is a major cause of global disability and improving management is essential. Acceptance and Commitment Therapy (ACT) is a promising treatment for chronic pain but has not been modified for physical therapy. This randomized controlled trial (RCT) compared physical therapy informed by Acceptance and Commitment Therapy (PACT) against standard care physical therapy for patients with CLBP. Patients with CLBP (duration ≥12 weeks, mean 3 years) were recruited from physical therapy clinics in four UK public hospitals. The Roland-Morris Disability Questionnaire (RMDQ) at 3 months' post randomization was the primary outcome. 248 participants (59% female, mean age=48) were recruited and 219 (88•3%) completed measures at 3 and/or 12 months' follow-up. At 3 months, PACT participants reported better outcomes for disability (RMDQ mean difference =1•07, p=0•037, 95%CI -2•08 to -0•07, d=0•2), Patient Specific Functioning (p=0.008), SF12 physical health (p=0.032), and treatment credibility (p<0.001). At 12 months' follow-up there were no significant differences between groups. PACT was acceptable to patients and clinicians and feasible to deliver. Physical therapists incorporated psychological principles successfully and treatment was delivered with high (≥80%) fidelity. Our results may inform the management of CLBP, with potential benefits for patients, health care providers and society. PERSPECTIVE: Psychologically informed physical therapy has great potential but there are challenges in implementation. The training and support included in the PACT trial enabled the intervention to be delivered as planned. This successfully reduced disability in the short but not long term. Findings could inform physical therapists' treatment of CLBP.

The Hospital Anxiety and Depression Scale (HADS) is a scale originally developed for the assessment of anxiety and depression in hospitalized patients. Despite its wide diffusion, the HADS factorial structure has displayed inconsistent results, leaving doubts about its use in chronic musculoskeletal pain. The purpose of this study was to thoroughly assess the factorial structure of the HADS in patients with chronic pain and to give guidance for a potential refinement. Data from 2522 patients with chronic pain from the Amsterdam Pain (AMS-PAIN) cohort were analyzed through: (1) exploratory bifactor analysis based on a Schmid-Leiman orthogonalization, (2) confirmatory factor analysis comparing a unidimensional model, the original correlated factors model and a bifactor model, (3) item response theory (IRT) analysis based on the graded response model. The results of the confirmatory factor analysis and of the IRT analysis were then cross – validated in an independent sample of patients with chronic pain (n = 8604). Both exploratory and confirmatory analyses revealed the presence of a strong general emotional distress factor, suggesting that the HADS can be used as a unidimensional scale. The IRT analysis led to the exclusion of three items and to the recoding of one item. The refined 11-item HADS scale was successfully cross-validated and confirmed as a unidimensional, locally independent, monotonic and reliable scale. Perspective: An 11-item shorter version of the HADS could be used to measure emotional distress in patients with chronic musculoskeletal pain. Given its unidimensionality, the use of its total score seems appropriate.

Previous studies have documented that racial minorities and women receive poorer pain care than their demographic counterparts. Providers contribute to these disparities when their pain-related decision-making systematically varies across patient groups. Less is known about racial and gender disparities in children with pain or the extent to which providers contribute to these disparities. In a sample of 129 medical students (henceforth referred to as 'providers'), Virtual Human methodology and a pain-related version of the Implicit Association Test (IAT) were used to examine the effects of patient race/gender on providers' pain assessment/treatment decisions for pediatric chronic abdominal pain, as well as the moderating role of provider implicit pain-related race/gender attitudes. Findings indicated that providers rated Black patients as more distressed (mean difference [MD]=2.33, p<.01, SE=.71, 95% CI=.92, 3.73) and as experiencing more pain-related interference (MD=3.14, p<.01, SE=.76, 95% CI=1.63, 4.64) compared to White patients. Providers were more likely to recommend opioids for Black patients than White patients (MD=2.41, p<.01, SE=.58, 95% CI=1.05, 3.76). Female patients were perceived to be more distressed by their pain (MD=2.14, p<.01, SE=.79, 95% CI=.58, 3.70) than male patients, however there were no gender differences in treatment recommendations. IAT results indicated that providers held implicit attitudes that Black Americans (M=.19, SD=.29) and males (M=.38, SD=.29) were more pain-tolerant than their demographic counterparts; however, these implicit attitudes did not significantly moderate their pain assessment/treatment decisions. Future studies are needed to elucidate specific paths through which the pain experience and care of children differ across racial and gender groups. PERSPECTIVE: Providers' pain assessment (i.e., pain distress/pain interference) and treatment (i.e., opioids) of pediatric pain differs across patient race and to a lesser extent, patient gender. This study represents a critical step in research on pain-related disparities in pediatric pain.

Opioid prescription in the treatment of chronic pain is frequent and carries a risk of increased morbidity and mortality in a clinically significant number of patients, particularly those who are using opioids in a hazardous manner. Few treatment options are available that target both pain-related interference and hazardous opioid use among patients with chronic pain. In military Veterans, this issue is of particular importance as numerous reports indicate continued high rates of opioid prescription for chronic pain, as well as significant opioid-related problems. The overall aim of the present study was to determine the feasibility of an integrated psychosocial treatment in Veterans with chronic pain, who also have evidence of hazardous opioid use. To examine this aim, a random design was used to assess the feasibility and initial efficacy of integrating two empirically supported interventions: Acceptance and Commitment Therapy for chronic pain and Mindfulness Based Relapse Prevention for opioid misuse. Half of participants were randomized to the integrated treatment group and all participants received usual care (UC) through a Veteran's Administration co-occurring disorders medical clinic to treat chronic pain and opioid misuse. In total, 37 participants were randomized and included in intent to treat (ITT) analyses and 32 individuals were included in per protocol (PP) analyses with 6-month follow-up serving as the primary study endpoint. Feasibility indicators included recruitment, retention, and treatment completion rates. Recruitment fell short of targeted enrollment, although retention and completion were excellent. Primary outcome measures were opioid misuse, pain interference, and pain behavior. Simultaneous multiple regression analyses controlled for pain duration, baseline opioid dose, and baseline value for outcome measures. Results of both the ITT and PP indicated a significant effect in favor of the integrated intervention for opioid misuse, pain interference, and pain behavior. Results support the feasibility of providing an integrated treatment for both opioid risk and pain interference. PERSPECTIVE: Opioid misuse occurs in some opioid-prescribed individuals with chronic pain. Few treatment options exist that target both pain interference and opioid misuse. This study examined feasibility and initial efficacy of an integrated behavioral treatment for Veterans. Feasibility was supported, except recruitment. Efficacy was supported compared to usual care.