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David Craig, PharmD | Editor

Summaries

Journal of Pain Summaries

Highlights from The Journal of Pain (Volume 19, No. 5, May 2018 Issue)

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Number and Type of Posttraumatic Stress Disorder Symptom Domains Are Associated with Patient-Reported Outcomes and Patients with Chronic Pain

Dale J. Langford, Brian R. Theodore, Danica Balsiger, Christine Tran, Ardith Z. Doorenbos, David J. Tauben, Mark D. Sullivan; Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, WA

Symptoms of posttraumatic stress disorder (PTSD) are significantly related to a broad array of pain-related outcomes, according to new research published in The Journal of Pain.

Population-based data from the National Comorbidity Survey show the prevalence of PTSD in patients with chronic pain is nearly four times higher than in the general population. Individuals with PTSD and concurrent chronic pain report increased pain intensity and greater pain-related disability than those without PTSD.

Researchers from the University of Washington examined the relationship between incremental increases in the number PTSD symptoms: intrusion, avoidance, hyperarousal and numbness/detachment. They noted that better understanding of the complex relationship between PTSD symptoms and the multidimensional experience of chronic pain is necessary for optimal comprehensive pain care.

For the study, 4,400 consecutive patients seeking care for chronic pain at the University of Washington completed an initial Pain Tracker web-based outcome assessment. PTSD was measured with a screening questionnaire developed by the VA to check for PTSD in primary-care settings. Subjects were asked, “In your life, have you had an experience that was so frightening, horrible, or upsetting that in the past month you ….” It was followed by probing four PTSD symptoms: intrusion (unwanted nightmares, thoughts, or situations that are reminders of the experience,) avoidance (avoiding thoughts or situations that are reminders,) hyperarousal (constantly on guard or easily startled), and numbness or detachment from others, activities, or surroundings.

Results of the analysis showed 27% of patients were positive for PTSD and highlighted the important role of numbness or detachment compared to other symptoms in contributing to adverse pain-related outcomes. “We cannot verify that PTSD symptoms are causing patients to experience worse pain-related outcomes, but it suggests there is a strong relationship that should be studied with longitudinal data,” the authors concluded. “Compared to patients with no symptoms, patients who reported two PTSD symptoms reported greater pain intensity and pain interference, greater pain-related disability, more severe depressive and anxiety symptoms, poorer HROOL, and greater risk of opioid misuse than those without PTSD symptoms.”

Acupuncture for Chronic Pain: Update of an Individual Patient Data Meta-Analysis

Andrew J. Vickers, Emily A. Vertosick, George Lewith, Hugh MacPherson, Nadine E. Foster, Karen J. Sherman, Domnick Irnich, Caludai M. Witt, Klaus Linde on behalf of the Acupuncture Trialists’ Collaboration

Although acupuncture is still considered a controversial treatment for chronic pain, several randomized trials have shown it can be effective in treating several pain conditions. However, there continues to be a lack of substantial data proving how insertion of needles on specific points of the body could lead to long-term decreases in pain.

A multicenter team from the Acupuncture Trialists Collaboration updated their previous meta-analysis, published in 2008, to determine the efficacy of acupuncture in treating four chronic pain conditions. Outcomes measured were pain relief and improved function. The updated meta-analysis included data from 10 additional trials, increasing the total to 39 trials involving nearly 21,000 patients.

Results affirmed previous findings. Acupuncture was superior to no acupuncture and a sham procedure for each pain condition, and there was clear evidence that the effects of acupuncture persist over time. “We confirmed that although the effects of acupuncture are not completely explicable in terms of placebo effects, factors other than the specific points of needling at correct acupuncture point locations are important contributors to acupuncture treatment benefit. Effects of acupuncture appear to persist over at least a 12-month period,” the authors concluded.


Clinical Journal of Pain Summaries

Highlights from The Clinical Journal of Pain (Volume 34, No. 5, May 2018 Issue)

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Correlates and Importance of Neglect-Like Symptoms in Complex Regional Pain Syndrome

Matthias Wittayer, Violeta Dimova, Frank Birklein, and Tanja Schlereth; Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Department of Neurology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany; Department of Neurology, DKD Helios Clinic Wiesbaden, Wiesbaden, Germany

Self-reported neglect-like symptoms (NLS) are common in complex regional pain syndrome (CRPS). Symptoms include a need to refocus attention on the affected limb to gain motor control, limb detachment, involuntary limb movements, and “dead” feelings. In clinical neurology the term “neglect” denotes inattention to sensory stimuli contralateral to a lesion of the temporoparietal junction, inferior parietal cortex, or superior temporal cortex of the right hemisphere. In this study, investigators sought to identify evidence for the origin and clinical meaning of NLS. They investigated NLS and related clinical, neurocognitive, and psychological findings in a large sample of patients with acute and chronic CRPS. They also assessed the impact of NLS on pain outcomes after treatment as usual.

NLS was assessed in a group of 53 patients with CRPS and results were compared to those of 28 healthy volunteers. To define the origin of the NLS reports, investigators tested the subjective visual midline and performed a limb-laterality recognition test and quantitative sensory testing. Psychological and pain assessment scales also were completed. Results were analyzed with univariate and multivariate approaches, and after 6 months, patients were reassessed and the influence of NLS on pain outcome was determined. The study’s primary finding was that NLS in CRPS are related to sensory and psychological function, depending upon disease duration. Although low pain intensity and high pain catastrophizing are related to NLS in acute CRPS, NLS in chronic CRPS is associated with a loss of thermal perception and high anxiety; this indicates that the meaning of NLS reported by the patients probably changes with CRPS duration. High NLS at baseline was related to a poor pain outcome after 6 months in chronic CRPS but not in acute CRPS. In contrast to pioneering studies’ findings, patients with CRPS in this study did not take longer to correctly recognize their affected limb. Patients in general took longer than controls, but there was no difference in recognition time between the affected and unaffected limb.

NLS reports from patients with CRPS were not direct correlates of neurocognitive disturbances in this study and instead appear to integrate pain control, pain catastrophizing, insufficient sensory processing, and anxiety. In the setting of acute CRPS, pain prevention efforts may train patients to not use their limb; for patients who train “successfully,” CRPS might enter a chronic phase with NLS becoming part of the disease. Early NLS screening and early treatment during the acute CRPS phase by targeting pain catastrophizing with graded exposure therapy might, for example, result in an optimal outcome.

Neuroinflammation of the Spinal Cord and Nerve Roots in Chronic Radicular Pain Patients

Daniel S. Albrecht, Shihab U. Ahmed, Norman W. Kettner, Ronald J. H. Borra, Julien Cohen-Adad, Hao Deng, Timothy T. Houle, Arissa Opalacz, Sarah A. Roth, Marcos F. Vidal Melo, Lucy Chen, Jianren Mao, Jacob M. Hooker, Marco L. Loggia, and Yi Zhang; Department of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Logan University, Chesterfield, MO; Medical Imaging Centre of Southwest Finland, Department of Diagnostic Radiology, Turku University Hospital, Turku, Finland; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; Department of Electrical Engineering, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada; Functional Neuroimaging Unit, CRIUGM, Université de Montréal, Montreal, QC, Canada; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston

Lumbar radiculopathy is one of the most common chronic pain disorders. Patients present with low back pain radiating along the lower extremity (i.e., sciatica) along the dermatomes innervated by the affected spinal nerve roots. Lumbar radiculopathy can be the result of multiple etiologies including disk herniation, radiculitis, and lumbar spinal stenosis. Despite the wealth of preclinical information and knowledge demonstrating that inflammation is associated with the initial acute phase of lumbar radicular pain, the role of neuroinflammation in chronic lumbar radiculopathy remains unknown. This study’s investigators used simultaneous positron emission tomography/magnetic resonance (PET/MR) imaging and the radioligand [11C] PBR28, which binds to the inflammatory marker 18 kDa translocator protein (TSPO, formerly known as the peripheral benzodiazepine receptor), to test the hypothesis that lumbar radiculopathy is associated with immunoactivation at the level of both the intervertebral foramina (i.e., neuroforamina, which include dorsal root ganglion and nerve roots) and spinal cord. They hypothesized that patients demonstrating neuroforaminal inflammation would benefit most from an anti-inflammatory procedure targeting the neuroforamen.

This study’s findings reveal that patients demonstrate elevated TSPO levels, a putative marker of immune activation, in both nerve roots (ipsilateral to the symptomatic leg) and in the spinal cord (in spinal segments known to process sensory information from the legs). These findings support the role of immunoactivation of the nerve roots as well as glial activation in the central nervous system as key components of the pathophysiology of chronic radicular pain. Immune responses in both central and peripheral nervous systems may represent a promising therapeutic target. In the treatment of chronic sciatica pain and besides targeting spinal nerve roots with epidural steroid injection as in current clinical practice, central immune activation also may need to be targeted for therapeutic intervention, as suggested by numerous preclinical studies.

Large-scale studies are warranted to elucidate the relationship between these inflammatory signals and symptoms and their viability as possible therapeutic targets and disease biomarkers. With validation in larger samples, these data suggest that preselecting patients based on the presence and/or magnitude of neuroforaminal inflammation might improve overall treatment response. It is important to note, however, that nearly all patients who were positive responders also had a high-affinity binding TSPO genotype (one patient was the exception). These preliminary observations are in line with previous preclinical literature supporting a role for neuroimmune activation in the establishment and/or maintenance of persistent pain conditions.


PAIN Summaries

Highlights from PAIN (Volume 159, No. 5, May 2018 Issue)

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Stigma and Pain in Adolescents Hospitalized for Sickle Cell Vasoocclusive Pain Episodes

Sarah R. Martin, Lindsey L. Cohen, Ifigenia Mougianis, Anya Griffin, Soumitri Sil, and Carlton Dampier; Department of Psychology, Georgia State University; Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta; Department of Pediatrics, Emory University, Atlanta, GA; and Department of Anesthesia, Perioperative, and Pain Medicine, Stanford Medicine, Stanford, CA

Numerous studies have identified reciprocal associations among sickle-cell disease (SCD) pain–related functional impairment, psychosocial factors such as social support, and quality of life (QOL). For example, research has found that pain interference is associated with lower QOL in youth with SCD. Youth with SCD also report more social impairments than their peers. The aims of this study were to examine associations among SCD-related stigma, pain interference, social support, and QOL in a sample of adolescents with SCD hospitalized for pain and to examine whether SCD-related stigma, pain interference, social support, and QOL were associated with hospital outcomes (i.e., loneliness, change in pain, and length of stay [LOS]). It was hypothesized that higher perceived stigma, higher pain interference, lower social support, and lower QOL would be associated with higher loneliness, less reduction in pain, and longer LOS during hospitalizations.

Descriptive statistics suggest that this sample of adolescents hospitalized with SCD pain reported higher stigma than patients with epilepsy and mental health conditions and stigma similar to reports of another sample of youth with SCD. In this study, pain interference was higher, QOL was lower, loneliness was lower, and social support was higher seen in other comparable samples. The sample generally endorsed moderate stigma, high pain interference, high social support, and low QOL. The patients reported low levels of loneliness, had moderate pain reduction during their hospital stay, and were hospitalized for approximately 5 days. Although more favorable levels of social support and loneliness were reported in this sample, higher levels of pain interference, lower QOL, and long LOS suggest that this sample may represent a more severe SCD group.

Patients’ reports of SCD-related stigma were related to poorer pain reduction over the course of hospitalization and higher loneliness. Investigators expected social support to be associated with stigma, pain interference, and other variables; however, social support did not correlate with any study variables and QOL was unrelated to hospital outcomes, which is inconsistent with prior research that reported a negative association between hospital admissions and QOL.

Future exploration of the ways in which SCD-related racial stigmas intersect and how these factors play a role in pain management and pain treatment is warranted. Future work also should explore the effects of medical and social contexts on stigma and whether reported perceived stigma is state or trait dependent or associated with frequency of past experiences, with stigmatization associated with hospital outcomes in youth with SCD. These data reinforce the notion that pain interference should be considered during pain assessment when considering how a patient is progressing toward discharge.

Reductions in Perceived Injustice Are Associated with Reductions in Disability and Depressive Symptoms After Total Knee Arthroplasty

Esther Yakobov, Whitney Scott, William D. Stanish, Michael Tanzer, Michael Dunbar, Glen Richardson, and Michael J. L. Sullivan; Departments of Psychology Surgery, McGill University Montreal, Canada; Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, UK; and Department of Surgery, Dalhousie University Halifax, Canada

Perceived injustice (PI) has been defined as an appraisal process characterized by attributions of blame, a sense of unfairness, and a tendency to construe one’s losses as severe and irreparable. Perceptions of injustice have been prospectively associated with poor recovery outcomes in patients with musculoskeletal injuries. Elevated presurgical scores on a measure of perceived injustice are prospectively associated with persistent pain 1 year following knee replacement surgery. And in several studies of people with whiplash injuries, PI helped to predict the persistence of posttraumatic and depressive symptoms following rehabilitation treatment. Although research consistently shows a relationship between PI and problematic recovery outcomes, little is known about the factors that contribute to the development and maintenance of perceptions of injustice.

The primary objective of this study was to examine whether reductions in symptom severity (i.e., pain and depressive symptoms) and disability following total knee arthroplasty (TKA) contributed to reductions in perceptions of injustice. Participants completed measures of PI, depressive symptom severity, pain severity, and disability before surgery and at 1-year follow-up. Regression analyses were used to examine whether postsurgical reductions in symptom severity and disability were associated with reductions in perceptions of injustice. It was hypothesized that PI would decrease as a function of post-TKA reductions in symptom severity and disability.

The study sample consisted of 69 women and 41 men with severe knee osteoarthritis who were scheduled to undergo TKA. Findings extend previous research by showing that reductions in depressive symptom severity and disability contributed to reduction in perceptions of injustice. Reductions in depressive symptoms were associated with reductions in PI even when controlling for reductions in disability. It appears that reductions in depressive symptoms after TKA might trigger a reappraisal of injustice cognitions. Future research is needed to explore the processes by which reductions in depressive symptomatology lead to reductions in PI and determine whether psychosocial interventions that target depressive symptoms and perceptions of injustice might promote more successful recovery following TKA.