November 2016
David Craig, PharmD | Editor


The Journal of Pain

Highlights from The Journal of Pain (Volume 17, No. 11, November 2016 Issue)

Journal of Pain cover

Child and Family Antecedents of Pain During the Transition to Adolescence: A Longitudinal Population-Based Study

Emily Incledon, Meredith O-Connor, Rebecca Giallo, George A. Chalkiadis, Tonya M. Palermo; Department of Paediatric Anaesthesia and Pain Management, Royal Children's Hospital, Melbourne, Australia; Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia; RMIT University, Melbourne, Australia; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA

A new study published in The Journal of Pain reported that children who experience pain at age 10 years may be at risk for continued pain problems in adolescence, and sleep difficulties might be the best predictor for childhood and adolescent pain problems.

Australian researchers used population-based data from the Longitudinal Study of Australian Children and adopted a biopsychosocial- and ecological-system approach to investigate child, family, and sociodemographic factors associated with pain problems in children transitioning into adolescence. They sought to describe the location, frequency, and severity of pain in late childhood (ages 10–11 years) and early adolescence (ages 12–13 years) and determine predictors in late childhood for pain problems in early adolescence. The authors noted that few population studies have investigated a broad range of child and family factors for determining which hold the most promise as targets for early intervention efforts and prevention.

Studies have shown that effective prevention and early intervention are essential to avoid risk for ongoing pain problems in adolescence. The peak onset of persistent pain occurs during adolescence, which makes late childhood, or the transition to adolescence, a critical development window for clinical intervention.

Data from the analysis showed that approximately 11% of children ages 10–13 years reported pain symptoms to their parents, and headache was the most common symptom. Results also suggested that children ages 10–11 years who had pain occurring one to seven times a week had a 26% greater risk for pain in early adolescence than children with no pain.

The authors concluded that pain in late childhood occurring at least weekly might be a useful marker to identify children at highest risk for recurring pain problems, and those children would benefit from clinical interventions. Further, sleep deficiency was identified as a significant predictor for pain symptoms. Sleep deficiency at ages 10–11 years was associated with two times greater odds for pain problems in early adolescence.

Perceived Injustice Is Associated with Pain and Functional Outcomes in Children and Adolescents with Chronic Pain: A Preliminary Examination

Megan M. Miller, Eric L. Scott, Zina Trost, Adam T. Hirsh; Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, IN; Department of Psychiatry, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN; Department of Psychology, University of Alabama Birmingham, Birmingham, AL

Studies have shown that injustice perceptions held by adults about their pain problems are associated with higher pain intensity, depression, and catastrophizing. A new study published in The Journal of Pain shows that this relationship also is relevant for adolescents with persistent pain.

Researchers from Indiana University and other centers hypothesized that injustice perceptions about pain also pertain to pain experiences in adolescents. They hypothesized that higher levels of injustice perceptions are associated with pain intensity; functional disability; and emotional, social, and school functioning.

Injustice perceptions involve feelings of unfairness and blame regarding an individual’s pain condition, which negatively effects emotional reactions to pain.

For the study, 139 adolescents with pain completed measures designed to evaluate perceptions about pain, pain intensity, catastrophizing, emotional functioning disability, and social and school functioning.

Results showed that greater perceived injustice about pain in the adolescents studied was associated with higher pain intensity, catastrophizing, and functional disability as well as poorer emotional, social, and school functioning. The findings suggest that injustice perceptions about pain can be reliably measured in children and adolescents and are important contributors to their pain experiences.


Highlights from PAIN (Volume 157, No. 11, November 2016 Issue)

Pain Medicine Cover

Mindfulness-Based Stress Reduction and Cognitive Behavioral Therapy for Chronic Low Back Pain: Similar Effects on Mindfulness, Catastrophizing, Self-Efficacy, and Acceptance in a Randomized Controlled Trial

Judith A. Turner, Melissa L. Anderson, Benjamin H. Balderson, Andrea J. Cook, Karen J. Sherman, Daniel C. Cherkin; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; Group Health Research Institute, Seattle

Cognitive behavioral therapy (CBT) has been demonstrated effective and is widely recommended for chronic pain problems. Mindfulness-based interventions (MBIs) also show promise for patients with chronic pain, and their use among this population is increasing. Key CBT mechanisms of action for chronic pain include decreased catastrophizing and increased self-efficacy for managing pain. However, little is known about the associations among pain catastrophizing, self-efficacy, acceptance, and mindfulness before psychosocial treatment or about differences in the effects of CBT versus MBIs on these variables.

The aim of this study was to replicate and extend previous research by using data from a randomized controlled trial comparing mindfulness-based stress reduction (MBSR), CBT, and usual care (UC) for chronic low back pain and to examine baseline relationships among measures of mindfulness and pain catastrophizing, self-efficacy, acceptance, and short- and long-term changes in the three treatment groups. Based on theory and previous research, investigators hypothesized that (1) at baseline, catastrophizing would be inversely related to acceptance, self-efficacy, and three dimensions of mindfulness (nonreactivity, nonjudging, and acting with awareness) but not associated with the observing dimension of mindfulness; (2) at baseline, acceptance would be associated positively with self-efficacy; and (3) from baseline to 26 and 52 weeks, acceptance and mindfulness would increase more with MBSR than with CBT and UC, and catastrophizing would decrease more and self-efficacy would increase more with CBT than with MBSR and UC.

The two interventions were comparable in format (group), duration, frequency, and number of participants per group cohort. Both the MBSR and CBT interventions consisted of 8 weekly, 2-hour sessions supplemented by home activities. For each intervention, researchers developed a therapist/instructor’s manual and participant’s workbook, both with structured and detailed content for each session. In each intervention, participants were assigned home activities, and there was emphasis on incorporating intervention content in their daily lives.

The hypotheses that MBSR and CBT would differentially affect measures of constructs believed to be therapeutic mechanisms generally were not confirmed. Investigators found no long-term effects of either treatment relative to UC on mindfulness. Catastrophizing decreased more posttreatment with MBSR than with CBT. Both treatments were effective when compared with UC in decreasing catastrophizing at 52 weeks. Although previous studies demonstrated reductions in catastrophizing after both CBT and MBIs, this study was the first to demonstrate similar decreases for both treatments with effects up to 1 year. Pain self-efficacy did not increase more with CBT than with MBSR at any point. These results suggest the potential value of refining both measures and models of mechanisms of psychosocial pain treatments to more comprehensively and efficiently capture key constructs important in adaptation to chronic pain.

Efficacy and Tolerability of Buccal Buprenorphine in Opioid-Experienced Patients with Moderate to Severe Chronic Low Back Pain: Results of a Phase 3, Enriched Enrollment, Randomized Withdrawal Study

Joseph Gimbel, Egilius L. H. Spierings, Nathaniel Katz, Qinfang Xiang, Evan Tzanis, Andrew Finn; Arizona Research Center, Phoenix, AZ; Department of Neurology, Craniofacial Pain Center, Tufts University Schools of Medicine and Dental Medicine, Boston; Analgesic Solutions, LLC, Natick, MA; Tufts University, Boston; Endo Pharmaceuticals Inc., Malvern, PA; BioDelivery Sciences International Inc., Raleigh, NC

The aim of this study was to determine the analgesic efficacy of buccal film of buprenorphine (BBUP) administered every 12 hours in opioid-experienced patients (including those taking up to 160 mg/d morphine sulfate equivalent [MSE]) with moderate to severe chronic low back pain (CLBP) and using around-the-clock opioid analgesics for an extended period. A BBUP has been developed and approved for chronic pain that is severe enough to necessitate around-the-clock, long-term opioid treatment (Belbuca, Endo Pharmaceuticals, Malvern, PA).

The present double-blind, placebo-controlled, randomized withdrawal study evaluated BBUP in patients with CLBP being treated with 30 to 160 mg MSE per day. The study used an enriched population that met the criteria for response to and tolerance of BBUP to determine the analgesic efficacy of BBUP relative to placebo. Patients entered the open-label titration phase with moderate to severe pain as indicated by their numerical rating scale pain assessments and with a significant amount of self-perceived disability attributable to their CLBP.

Treatment with BBUP at doses up to 900 mg twice daily effectively controlled moderate to severe CLBP in an opioid-experienced population (30–160 mg/d MSE) over the 12-week, double-blind period with significant differences on the Patient Global Impression of Change scale. BBUP was generally well tolerated; there was no evidence of respiratory depression in this large population. In addition, rates of opioid-associated gastrointestinal adverse events (nausea, constipation, and vomiting) were low, ranging from 3% to 8%. During open-label treatment, when opioid-experienced patients were switched from their current around-the-clock opioid to BBUP, the rate of drug withdrawal syndrome was low. Furthermore, there was a high level of compliance with the BBUP. Patient satisfaction was indicated by the high percentage of completers and people who continued in a subsequent long-term safety study.

The Clinical Journal of Pain

Highlights from The Clinical Journal of Pain (Volume 32, No. 11, November 2016 Issue)


Randomized, Sham-Controlled, Double-Blind, Multicenter Clinical Trial to Ascertain the Effect of Percutaneous Radiofrequency Treatment for Sacroiliac Joint Pain: Three-Month Results

Cornelis W. J. van Tilburg, Fleur A. Schuurmans, Dirk L. Stronks, Johannes G. Groeneweg, and Frank J. P. M. Huygen; Department of Anesthesiology, Multidisciplinary Pain Center, Bravis Hospital, Boerhaaveplein, Bergen op Zoom; Center for Pain Medicine, Erasmus University, Rotterdam, Netherlands

For patients with sacroiliac (SI) joint pain (constituting 10% to 38% of patients with chronic low back pain), questions arise concerning those who might be more susceptible to these problems, how the diagnosis should be made, and optimal treatments. Several treatments for SI joint pain are described in the literature; one of them is to apply radiofrequency (RF) current to the nerves that provide the innervation. The Simplicity III probe (Neurotherm, Wilmington, MA) is a multielectrode RF probe that has a unique design that allows for positioning using a single percutaneous entry point. During the procedure in which this probe is used, the lateral branches of S1, S2, S3, and S4 are targeted at the same time (a L5 dorsal root ramus RF lesioning is performed separately). In this randomized, controlled, double-blind, multicenter clinical trial, the percutaneous RF treatment of SI joint pain with this probe was evaluated and compared with a sham procedure. A randomized, sham-controlled, double-blind, multicenter clinical trial was conducted for patients experiencing SI joint pain for more than 3 months.

No statistically significant difference in pain level over time between the groups or in the factor group was found. However, the period factor yielded a significant difference: when pooled together, mean pain level was significantly reduced at T1 compared with T0. In the crossover group, 8 of 19 patients experienced a reduction on the numerical rating scale of two or more at 1-month crossover.

The proportion of patients who reported significant pain relief after undergoing the sham procedure was even higher (but not statistically significant) than the number describing pain relief after undergoing the actual treatment. In the crossover group (3 months after the sham procedure), the number of people who demonstrated statistically significant pain reduction after RF treatment was 42.1%, which was equal to the number of positive results (43.3%) from the primary treatment group. These results demonstrate that the hypothesis of no difference in pain reduction or global perceived effect between the treatment and sham group cannot be rejected.

Acute Low Back Pain: Differential Somatosensory Function and Gene Expression Compared with Healthy No-Pain Controls

Angela R. Starkweather, Divya Ramesh, Debra E. Lyon, Umaporn Siangphoe, Xioayan Deng, Jamie Sturgill, Amy Heineman, R. K. Elswick Jr, Susan G. Dorsey, and Joel Greenspan; University of Connecticut, School of Nursing, Storrs, CT; University of Florida College of Nursing, Gainesville, FL; Virginia Commonwealth University, School of Nursing, Richmond, VA; and University of Maryland School of Nursing, Baltimore, MD

Low back pain (LBP) is a musculoskeletal symptom defined as discomfort in the region between the thoracolumbar and lumbosacral junctions and is considered to be “acute” for up to 6 weeks after onset. An estimated 40% of individuals will experience persistent LBP lasting for more than 12 weeks. Researchers have focused on psychosocial and environmental risk factors to identify people at risk for persistent LBP through quantitative sensory testing (QST), which was primarily introduced to detect and differentiate between neuropathic syndromes. This study’s authors sought to describe and compare somatosensory responses to experimental pain and gene expression data between individuals with acute LBP and no-pain controls (NPCs) by comprehensively comparing QST parameters between no-pain control participants and those with acute LBP. Their hypothesis was that there would be significant differences in somatosensory function and gene expression profiles between the acute LBP group and the NPC group.

QST was performed in the lumbar region (at the location of pain for the acute LBP group) and on the dominant forearm (remote area). Participants in the acute LBP group had a lower threshold for cold at both the remote and back areas, meaning that pain was elicited at a higher temperature in the acute LBP group. The pressure pain threshold (PPT) only was significantly lower in the back area of the acute LBP group, meaning that less pressure stimulus was required to elicit pain. Mechanical sensitivity and the wind-up ratio were significantly higher in both the remote and back areas in the acute LBP group, meaning that the acute LBP group reported higher pain scores to a set mechanical stimulus. Finally, pain scores were significantly elevated in response to a standard brush applied to the painful back region in the acute LBP, suggesting mechanical allodynia.

This study indicates a unique profile of somatosensory alterations and differential gene expression present at the initial episode of acute LBP and reports these differences in comparison with NPCs. These findings suggest a mechanism of enhanced central nervous system excitability in participants with acute LBP. Deep tissue–specific peripheral sensitization was suggested in the acute LBP group because of significant differences in the PPT of the painful back area but not the remote body site. Although previous studies have reported sensory alterations among participants with chronic LBP, this study reports indications of selective peripheral and central sensitization among participants with acute LBP and NPCs. These preliminary findings provide evidence of potential candidate genetic markers that may influence pain signaling and inflammatory processes during the acute stage of pain. Future studies will examine these parameters in a longitudinal cohort to determine whether specific indicators of somatosensory function and gene expression contribute to persistent LBP.