April 2017
David Craig, PharmD | Editor


The Journal of Pain

Highlights from The Journal of Pain (Volume 18, No. 4, April 2017 Issue)

Study Tracks Origin and Duration of Opioid Use

Surgeons are the most common source of initial prescriptions for opioid pain medications, according to research published in The Journal of Pain. Surgeons would therefore likely benefit from interventions to both change their prescribing beliefs and improve patient education regarding risks associated with opioid use.

Researchers from the University of Pennsylvania hypothesized that better understanding of how opioid therapy is started is essential to determine if patients have been properly selected for this treatment. Recent reports suggest that opioid-prescribing decisions at the time of an injury or surgery may heighten the chances that patients continue taking the drugs for six months or longer.

For the study, the authors surveyed 115 patients receiving chronic opioid therapy. The lead question focused on the role of postoperative prescription habits in fostering opioid dependence and long-term use. Data from the survey responses showed the primary reasons to initiate opioid therapy were treatment of postoperative pain (27%) and pain from an acute injury (27%). Most patients received their initial prescriptions from a surgeon (30%), followed by pain physicians (29%) and primary care practitioners (21%).

More than a third of the study subjects received opioids initially to treat acute pain but progressed to chronic use without interruption of treatment. Also, post-operative complications were cited as a factor leading to longer and higher doses of opioids. High incidences of depression (43%), anxiety (23%) and medical history of aberrant behavior (32%) were reported by study subjects.

A key finding from the survey is that 1 in 4 respondents said they take opioids for a different reason than was indicated for the initial prescription. Therefore, patients receiving long-term opioid therapy often transition to chronic use after starting opioids for short-term treatment of postoperative or injury related pain. This finding raises concern regarding justification for continuation of opioids beyond the original indication. 

The authors concluded that prescribers must continually re-evaluate pain therapies and consider alternatives to opioids that could be effective. 

Higher Opioid Doses Linked with Worse Patient Outcomes

Several studies have shown that doses of opioid pain medications are a contributing factor for higher incidence of adverse events.  Compared to other analgesics, opioids are associated with increased likelihood for cardiovascular events, fractures, accidents and death.  Recent studies highlighted the relationship of higher opioid doses with elevated risk for overdose death. 

Researchers with Kaiser Permanente in Oregon hypothesized that patients taking the highest doses of opioids would report more pain, functional impairment, and mental health and substance abuse problems than those taking lower doses. The study evaluated 517 patients who were prescribed long-term opioid therapy, and the authors compared differences on pain and mental health variables based on prescription opioid doses.

Results showed that the study participants had high rates of comorbid psychopathology and alcohol and substance abuse. As the dose of opioids increased, so did pain intensity and pain-related disability. Also, depression was more prevalent in those taking high doses of opioids, and these patients had poorer expectations and confidence in their ability to perform tasks because of their pain. The data also showed greater utilization of health care services as prescription opioid doses increased.

The researchers concluded that poorer patient-reported pain outcomes are associated with higher opioid doses. 




Highlights from PAIN (Volume 158, No. 4, April 2017 Issue)

Pain Medicine Cover

Brief Telephone-Delivered Cognitive Behavioral Therapy Targeted to Parents of Children with Functional Abdominal Pain: A Randomized Controlled Trial

Rona L. Levy, Shelby L. Langer, Miranda A. L. van Tilburg, Joan M. Romano, Tasha B. Murphy, Lynn S. Walker, Lloyd A. Mancl, Robyn L. Claar, Melissa M. DuPen, William E. Whitehead, Bisher Abdullah; Kimberly S. Swanson, Melissa D. Baker, Susan A. Stoner, Dennis L. Christie, Andrew D. Feld; School of Social Work, University of Washington, Seattle; Center for Health Promotion and Disease Prevention, College of Nursing and Health Innovation, Arizona State University, Tempe, AZ; Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; Department of Pediatrics, Vanderbilt University, Nashville, TN; Oral Health Sciences, University of Washington, Seattle; Prime Health Clinic, Federal Way, WA; St. Charles Health System, Bend, OR; HealthPoint, Bothell, WA; Alcohol and Drug Abuse Institute, University of Washington, Seattle; Gastroenterology, Seattle Children’s Hospital, Seattle; Gastroenterology, Group Health Cooperative, Seattle

Functional abdominal pain disorders (FAPDs) such as functional abdominal pain and irritable bowel syndrome are associated with missed school days, reduced quality of life (QoL), and emotional distress in children and parents. FAPD is more common in girls; most prevalent between ages 8 and 11 years; and frequently is associated with nonspecific symptoms such as fatigue, dizziness, and headaches. Cognitive behavioral therapy (CBT) has been shown to reduce pain and disability in children with FAPD. This study compared three intervention conditions aimed at parents: social learning and CBT (SLCBT) delivered by phone, in-person SLCBT, and an attention-control condition delivered by phone (education and support condition by phone [ES-R]).

Parents in SLCBT conditions were instructed to reduce solicitous responses to child illness behaviors, to reduce appraisals of child symptoms as indicating harm or threat, and to encourage child wellness and adaptive coping. Investigators hypothesized that phone and in-person SLCBT would be equally effective and that both would be more effective than ES-R in changing the primary outcome of parent-reported child pain severity and secondary outcomes (process measures) of parental solicitousness, catastrophizing, and threat appraisals. They also hypothesized that children of parents receiving SLCBT would report greater improvement in the process measure of pain coping vs. controls. Participants included 316 children with FAPD (functional abdominal pain or irritable bowel syndrome) and their parents recruited between 2012 and 2015 from four pediatric gastrointestinal clinics.

Contrary to the hypothesis, there was no treatment effect on the primary outcome measure of pain severity as reported by parents. However, consistent with this study’s hypotheses, both SLCBT groups produced a significantly better improvement than ES-R on secondary outcomes (process measures) of parental solicitousness, catastrophizing, pain beliefs (threat appraisals), and parent-reported child emotion-focused and problem-focused coping. Parents in the two SLCBT conditions also reported greater improvements in functional disability, pain behaviors, and healthcare utilization for pain relative to controls, with phone-based SLCBT also showing greater improvement in parent-reported child QoL and school absenteeism than the control group. Parents also reported less healthcare utilization after treatment, which can provide further benefits such as fewer hours of missed work to attend medical visits.

Results generally were comparable for the in-person and phone-delivered SLCBT conditions, suggesting that this cost-effective method of delivery is not inferior to in-person interventions with parents. This finding supports the potential for remote delivery of such interventions, which can reduce barriers of cost and access and enable organizations to more easily offer these interventions. Participating parents were predominantly mothers (90%); although mothers most often are involved in children’s medical care, future studies are needed to examine whether paternal involvement could be equally effective or whether involving both parents (regardless of gender) could enhance efficacy of interventions.

Stress-Related Psychological Symptoms Contribute to Axial Pain Persistence After Motor Vehicle Collision: Path Analysis Results from a Prospective Longitudinal Study

Rose K. Feinberg, JunMei Hu, Mark A. Weaver, Roger B. Fillingim, Robert A. Swor, David A. Peak, Jeffrey S. Jones, Niels K. Rathlev, David C. Lee, Robert M. Domeier, Phyllis L. Hendry, Israel Liberzon, Samuel A. McLean; UNC Institute for Trauma Recovery, University of North Carolina, Chapel Hill; Departments of Anesthesiology and Medicine and Biostatistics, University of North Carolina, Chapel Hill; Department of Community Dentistry and Behavioral Science, University of Florida, Gainesville; Department of Emergency Medicine, William Beaumont Hospital, Royal Oak, MI; Department of Emergency Medicine, Massachusetts General Hospital, Boston; Department of Emergency Medicine, Spectrum Health System, Grand Rapids, MI; Department of Emergency Medicine, Baystate Medical Center, Springfield, MA; Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY; Department of Emergency Medicine, Saint Joseph Mercy Health System, Ypsilanti, MI; Department of Emergency Medicine, University of Florida, Jacksonville; Department of Psychiatry, University of Michigan, Ann Arbor; Department of Emergency Medicine, University of North Carolina, Chapel Hill

Motor vehicle collisions (MVCs) result in 50 million injuries worldwide and almost 4 million US emergency department (ED) visits each year. Many of these patients develop persistent musculoskeletal pain, and the most common and morbid location of such pain is the axial region (neck, shoulders, and/or back). Posttraumatic stress disorder (PTSD) symptoms including reexperiencing the MVC and avoiding reminders of the MVC; hyperarousal symptoms also are common in this population and may contribute to pain persistence through a number of mechanisms.

In this study, investigators used a path-analytic approach to evaluate whether longitudinal relationships between posttraumatic stress and axial pain symptoms after MVC support the hypothesis that PTSD symptom clusters promote axial pain persistence. Investigators hypothesized that hyperarousal and reexperiencing symptoms would partially mediate post-MVC axial pain persistence. They also hypothesized that increased hyperarousal symptoms would more strongly be associated with increased pain among individuals with increased genetic vulnerability to stress-induced pain. This study explored the relationship between hyperarousal and axial pain persistence among individuals with glucocorticoid receptor cochaperone FK506-binding protein 51 (FKBP5) haplotypes that are known to increase vulnerability to chronic post-MVC pain. In secondary analyses, investigators explored path differences over time among those with and without substantial early and persistent PTSD or axial pain symptoms. This prospective longitudinal study enrolled patients presenting to the ED within 24 hours of MVC. Data were collected at eight EDs in four no-fault MVC litigation/insurance states between February 2009 and October 2011.

Both substantial PTSD symptoms and moderate or severe axial pain symptoms were common in the cohort, with more than one in four participants having substantial PTSD symptoms and one in two having moderate or severe axial pain symptoms at 6 weeks. The correlation between PTSD and axial pain symptoms increased steadily over time, from 0.12 in the ED to 0.43 at 1 year. Path analysis results support the hypothesis that axial pain after MVC consistently promotes the maintenance of hyperarousal and intrusive symptoms from the early weeks postinjury through 1 year. In contrast, although one or more PTSD symptom clusters had an influence on axial pain outcomes throughout the year after MVC, the different symptom clusters were influential at different time points, with helplessness and anger most influencing axial pain severity during the initial weeks after MVC, hyperarousal symptoms most influencing (and partially mediating) axial pain persistence during the initial months after MVC, and intrusive symptoms partially mediating the persistence of axial pain at 1 year. In addition, PTSD symptoms (specifically, hyperarousal symptoms) had a greater influence on pain outcomes among individuals with increased genetic vulnerability to stress-induced pain. Relationships between pain and PTSD symptoms vary among those with substantial peritraumatic distress.

Although pain symptoms had a consistent augmenting effect on PTSD symptoms across time, these results indicate that the relative influence of different PTSD symptom clusters may be time dependent. Hyperarousal symptoms most influenced axial pain persistence during the initial months after MVC and may be most important to target with interventions during this time, with intrusive symptoms playing a greater role in maintaining/augmenting pain after chronic pain has developed. These findings indicate that constitutional (genetic) factors affect the influence of PTSD symptom clusters on chronic pain pathogenesis.

Further studies are needed to better understand the interplay of pain and PTSD symptoms during the aftermath of trauma. Such understanding will enable the development of optimal interventions to reduce the incidence of these common, highly morbid outcomes.

The Clinical Journal of Pain

Highlights from The Clinical Journal of Pain (Volume 33, No. 4, April 2017 Issue)


Measuring the Cognitions, Emotions, and Motivation Associated with Avoidance Behaviors in the Context of Pain: Preliminary Development of the Negative Responsivity to Pain Scales

Mark P. Jensen, L. Charles Ward, Beverly E. Thorn, Dawn M. Ehde, and Melissa A. Day; Department of Rehabilitation, University of Washington, Seattle

The Behavioral Inhibition System-Behavioral Activation System (BIS-BAS) model of pain proposes a set of six key domains that are hypothesized to explain the benefits of psychosocial pain treatments, including both negative and positive cognitive, emotional, and motivational responses to pain. The purpose of this study was to begin the process of developing measures of these domains to build the capacity to evaluate and modify the BIS-BAS model and to facilitate better understanding of the mechanisms of psychosocial pain treatments.

This study resulted in the development of three negative responses to pain (NRP) scales, each of which has support for its reliability and validity. Although the analyses yielded two positive response (PR) scales that are internally consistent, test-retest reliability and associations with validity coefficients suggest that further development of these scales is needed. The findings support the existence of two relatively independent overarching response factors, one of which comprises NRP and the other PRs to thoughts about valued activities. Moreover, the hypothesized stronger associations between the domains within each factor and weaker associations between the domains across the two factors were strongly supported; there seem to be two relatively independent “clusters” representing negative and positive responses. However, the findings were not entirely consistent with all of the tenets of the BIS-BAS model, as originally proposed.

This research yielded measures of three NRP domains: despondent responses, fear responses, and motivation for behavioral inhibition responses to pain. The resulting brief scales have strong psychometric properties, being related to each other and having validity criteria consistent with the theoretical model that informed this research. The findings suggest that some minor modificationsare warrented in the theoretical model upon which the NRP scales are based, making despondent and fear responses distinct within the model and possibly combining emotional and cognitive responses into a single domain, depending upon the outcome of future research. Research to further develop the PR to pain scale is needed before these scales can be recommended for use.

Widespread Pain Among Youth with Sickle Cell Disease Hospitalized with Vasoocclusive Pain: A Different Clinical Phenotype?

William T. Zempsky, Emily O. Wakefield, James P. Santanelli, Tamara New, Kimberly Smith-Whitley, James F. Casella, and Tonya M. Palermo; Connecticut Children’s Medical Center, Hartford, CT; Institute of Living at Hartford Hospital, Hartford, CT; University of Connecticut School of Medicine, Farmington, CT; Children’s Healthcare of Atlanta at Emory University School of Medicine, Atlanta; Children’s Hospital of Philadelphia, Philadelphia; Johns Hopkins School of Medicine, Baltimore; University of Washington and Seattle Children’s Research Institute, Seattle

Sickle cell disease (SCD) is a genetic red blood cell disorder characterized during childhood and adolescence by intermittent episodes of severe pain termed vasoocclusive episodes (VOE). VOE lasts for 2 to 9 days, frequently resulting in hospitalization and impacting distinct body areas that may vary with age, such as the hands and feet (infants and toddlers), long bones (children), and back and abdomen (adolescents). The frequency and intensity of pain become more severe as children age. Daily diary studies demonstrate that children with SCD report pain on 16% to 30% of days, with pain becoming more severe in adolescence as evidenced by a marked increase in use of opioids for pain management (57% of days in the 14- to 19-year-olds, but only 10% to 11% of days in younger age groups). Among adults, most experience chronic pain, with 55% of adult respondents reporting pain on more than half of the days and 29% reporting pain on 95% of days. Considering the ongoing nociceptive experience in youth with SCD, a subgroup of patients may exhibit widespread pain (WSP) during their hospitalizations with VOE.

In this study, investigators sought to describe pain distribution in youth hospitalized for VOE at four children’s hospitals. They hypothesized that youth with WSP would have higher pain scores and longer lengths of hospitalization, indicating a more severe pain phenotype. They also predicted that youth with SCD and WSP during hospitalization would also report more significant functional disability, pain, pain burden, decreased mood, and impaired quality of life versus youth without WSP.

Findings indicate that WSP can be detected in a subgroup of youth (approximately 20%) with a body pain diagram. This subgroup may represent a more severe clinical phenotype of SCD. Youth with WSP had higher pain scores, more significant functional disability, pain burden, decreased mood, and impaired quality of life versus youth without WSP.

These findings support the hypothesis that youth with WSP during hospitalization may represent a unique clinical phenotype that warrants future research. The clinical relevance of WSP in pediatric SCD remains to be determined but holds promise as a clinical phenotype that might be used in future intervention research to evaluate whether targeting centralized pain may be appropriate for youth with SCD.