May 2016
David Craig, PharmD | Editor


The Journal of Pain

Highlights from The Journal of Pain (Volume 17, No. 5, May 2016 Issue)

Journal of Pain cover

State Plan Lowers High-Dose Opioid Use in Medicaid Patients

Mark D. Sullivan, Amy M. Bauer, Deborah Fulton-Kehoe, Renu K. Garg, Judith A. Turner, Thomas Wickizer, Gary M. Franklin; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA; Department of Rehabilitation Medicine, University of Washington, Seattle, WA; Department of Health Services, University of Washington, Seattle, WA; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA; Department of Neurology, University of Washington, Seattle, WA; Washington State Department of Labor and Industries, Olympia, WA

The state of Washington in 2007 released its “WA Interagency Guideline on Opioid Dosing for Chronic Non-Cancer Pain” in the wake of the state’s high opioid-related mortality rate, which was 50% above the national average. Medicaid recipients in Washington showed nearly six times the rate of opioid mortality than commercially insured patients.

Researchers from the University of Washington reported in The Journal of Pain that the guideline helped achieve a significant decline in high-dose opioid use in the state’s Medicaid population.

The Washington guideline was the first in the nation to specify dosing recommendations, and also gave guidance about patient selection and risk assessment, initiating and discontinuing opioid therapy, and transitioning to chronic therapy. Among recommended practices is a recommendation that providers not exceed a dosing threshold of a 120 mg morphine-equivalent dose per day for patients who did not have clinically meaningful improvement to pain and function without first obtaining a pain specialist consultation.

The authors noted that their study was the first to show a decline in high-dose opioid prescribing within the Medicaid population. Results suggest that opioid treatment guidelines with dosing guidance may be able to reduce high-dose opioid use without affecting median dose use.

Pain Sensitivity in Patients with Major Depression

Marco Hermesdorf, Klaus Berger, Bernhard T. Baune, Jürgen Wellmann, Ruth Ruscheweyh, Heike Wersching; Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany; Discipline of Psychiatry, University of Adelaide, Adelaide, Australia; Department of Neurology, University of Munich, Munich, Germany

Studies suggest that three in four patients with depression complain about having pain and, likewise, chronic pain is associated with increased risk for depression. However, the relationship between depression and pain sensitivity is not completely understood.

Researchers from three German and Australian universities investigated different dimensions of pain sensitivity and assessed pain thresholds and self-rated pain intensity in a large cohort of 735 patients with a current episode of major depression and compared them with 456 healthy control participants.

Results of the analysis showed that patients with depression had increased pain sensitivity compared with non-depressed patients, based on low-pressure pain thresholds and higher Pain Sensitivity Questionnaire (PSQ) scores. This supports previous findings of increased pain prevalence in depressed patients.

Also, among patients with depression, severity of anxiety symptoms was the strongest clinical predictor of PSQ scores. The authors recommend that clinicians consider the role of anxiety in treatment programs for pain in patients with depression.


Highlights from PAIN (Volume 157, No. 5, May 2016 Issue)

Pain Medicine Cover

Trends in Opioid Prescriptions Among Children and Adolescents in the United States: A Nationally Representative Study from 1996 to 2006

Cornelius B. Groenewald, Jennifer A. Rabbitts, Thomas Gebert, Tonya M. Palermo; Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, WA; Department of Neurobiology, University of Washington College of Arts and Sciences and School of Medicine, Seattle, WA; Departments of Psychiatry and Pediatrics, University of Washington School of Medicine, Seattle, WA

Opioid addiction is the fastest-growing drug problem among adolescents in the United States. Among 12th-grade students, 8.7% reported opioid misuse during the past year. In addition, rising numbers of adult opioid prescriptions are associated with increased rates of opioid poisoning and overdose among children and adolescents who have access to these substances at home. An understanding of the epidemiology of opioid prescribing patterns is critical to identify the scope of the problem and begin to address opioid misuse and poisonings.

This study’s objective was to examine patterns of opioid prescriptions among children and adolescents ages 0 to 17 years in the United States between 1996 and 2012 using a set of nationally representative large databases, the Medical Expenditure Panel Surveys (MEPS). The primary aim was to estimate the effects of time and sociodemographic and clinical characteristics on opioid prescriptions to children and adolescents. The primary hypothesis was that prescription opioid use among children and adolescents would increase over time. Investigators hypothesized that rates of opioid prescription to family members of children and adolescents also would increase over time. Data on all 144,918 children and adolescents (average 9,057 each year) in the 1996 to 2012 MEPS databases were collected. Although there were significant differences in year-to-year opioid prescriptions, the overall trend showed stability over time in prescriptions to children and adolescents. On average, 2.86% of children and adolescents received an opioid prescription each year between 1996 and 2012.

Sociodemographic characteristics associated with higher rates of opioid prescriptions between 1996 and 2012 include being white and non-Hispanic and having private or public insurance from a region other than the Northeastern United States. Poorer parent-reported physical and mental health also was associated with a higher likelihood of prescription opioid use. The most common opioids prescribed to children and adolescents between 1996 and 2012 were codeine, hydrocodone, and oxycodone; in 2012, codeine, hydrocodone, and oxycodone were prescribed to 39.9%, 42.1%, and 15.5% of children and adolescents, respectively.

Contrary to their primary hypothesis, however, investigators found that trends in opioid prescriptions to children and adolescents in the United States remained stable between 1996 and 2012. In contrast, opioid prescriptions to family members of children and adolescents and to adults in general more than doubled between 1996 and 2012. The increased number of opioid prescriptions to adults in the community is concerning because this puts children and adolescents at higher risk for opioid misuse and poisoning because of a larger supply of available opioids.

Characterization of Risk Factors for Adjuvant Radiotherapy-Associated Pain in a Triracial/Ethnic Breast Cancer Population

Eunkyung Lee, Cristiane Takita, Jean L. Wright, Isildinha M. Reis, Wei Zhao, Omar L. Nelson, Jennifer J. Hu; Departments of Public Health Sciences and Radiation Oncology, University of Miami School of Medicine, Miami, FL; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, MD; Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, FL

Postsurgical adjuvant radiotherapy (RT) significantly reduces local-regional recurrence of early-stage breast cancer, so most patients with breast cancer receive RT after undergoing breast-conserving surgery (BCS). Breast RT is generally well tolerated, but acute skin toxicity, a common side effect, can result in bothersome symptoms including burning sensation, itching, tenderness, and pain. This prospective study was designed to characterize the risk factors associated with clinically relevant pain in patients with breast cancer who undergo postsurgery adjuvant RT. Investigators used a prospective study design to target a triracial/ethnic breast cancer population undergoing RT.

Women who had a new diagnosis with stages 0-III breast cancer and who were planning to receive adjuvant breast RT on their intact breast were recruited from the radiation oncology clinics at the Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital in Miami, FL. All patients underwent BCS with or without sentinel lymph node biopsy or axillary lymph node dissection (ALND). Adjuvant hormonal therapy was allowed before, during, or after RT at the discretion of a medical oncologist; however, concurrent chemotherapy was not allowed for study entry. The target study sample size is 1,000 patients. As of July 2014, 438 patients were screened and 399 patients enrolled.

Study findings suggest that RT increased clinically relevant pain (from 16% before RT to 31% after RT) in patients with breast cancer. Long-term follow-up of this population will shed light on whether RT-associated acute pain can predict chronic pain among breast cancer survivors. There were significant racial/ethnic disparities in clinically relevant pain before RT and after RT and RT-associated changes. The higher prevalence of pain in underserved minorities may be influenced by several cofactors. First, higher proportions of African Americans (62%) and Hispanic whites (38%) were obese compared with non-Hispanic women (24%), and obesity has been associated with chronic pain. Second, higher proportions of African Americans and Hispanic whites had more advanced tumors (stages IIA-IIIC), which may necessitate more aggressive treatments such as chemotherapy or ALND. These data suggest that pre-RT pain is an independent risk factor for post-RT pain, which is supported by previous studies. RT-associated pain can last for many decades, so pain management during RT may be an effective preventive measure. In terms of pre-RT pain management, both race/ethnicity and body mass index should be taken into consideration because these are the two risk factors for pre-RT pain.

The Clinical Journal of Pain

Highlights from The Clinical Journal of Pain (Volume 32, No. 5, May 2016 Issue)


Craniosacral Therapy for the Treatment of Chronic Neck Pain: A Randomized Sham-Controlled Trial

Heidemarie Halle, Romy Lauche, Holger Cramer, Thomas Rampp, Felix J. Saha, Thomas Ostermann, Gustav Dobos; Department of Internal and Integrative Medicine, Kliniken Essen-Mitte; University of Duisburg-Essen, Essen, Germany; Department of Psychology, Witten/Herdecke University, Witten, Germany; Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Sydney, Australia

Neck pain is a substantial problem in public health, with one in two people experiencing neck pain at least once during their lifetime. Neck pain is often recurrent, of nonspecific nature, and associated with disability in both social and occupational life. Evidence is still limited regarding treatment of chronic neck pain, and only therapeutic exercises, acupuncture, and manual therapies are recommended in recent clinical practice guidelines. Upon asking manual therapists about their perception and use of complementary and alternative medicine for the treatment of chronic pain conditions, craniosacral therapy (CST) is frequently mentioned. CST is regarded as a noninvasive, mindfulness-based treatment approach that employs gentle manual palpation techniques to release fascial restrictions between the cranium and the sacrum.

This study, which investigated the efficacy of CST in chronic, nonspecific neck pain in comparison with a manual sham control intervention, was a randomized controlled clinical trial with a parallel-group design and 3 months of follow-up observation. After baseline assessment, patients were randomized into either the CST group or an active attention-control group receiving light-touch sham treatment. Outcome measures were collected at week 8 after randomization (after intervention) and at week 20 (3-month follow-up); the primary outcome was average pain intensity during the last 7 days recorded on a 100-mm visual analog scale at week 8. Secondary outcomes were pain on movement, pressure pain sensitivity, neck pain–related disability, health-related quality of life, well-being, anxiety and depression, stress perception, pain acceptance, body awareness, patients’ global impression of improvement, and safety.

Significant and clinically relevant effects on pain intensity were found directly after the active treatment period and at week 20. Minimal clinically important differences in pain intensity at week 20 were reported by almost 78% within the CST group, whereas 48% experienced substantial clinical benefit. An exploratory analysis also revealed significant between-group differences at weeks 8 and 20 for pain upon movement, functional disability, physical quality of life, and global impression of improvement. Pressure pain sensitivity and body awareness were significantly improved only after 8 weeks of treatment, and anxiety only at week 20.

CST may be a worthwhile addition to standard medical care. Further studies with rigorous methodological designs and long-term follow-ups are needed to confirm CST efficacy in neck pain treatment.

Sleep Quality Among People Living with Chronic Noncancer Pain: Findings from the Pain and Opioids IN Treatment (POINT) Cohort

Patrick J. Tighe, Christopher D. King, Baiming Zou, Roger B. Fillingim; Pain Research and Intervention Center of Excellence (PRICE), University of Florida, Gainesville, FL; Departments of Anesthesiology and Biostatistics, University of Florida College of Medicine, Gainesville, FL

The goal of this retrospective cohort study was to characterize sustained postoperative pain relief (SuPPR) conceptually in a group of adults undergoing major surgery. SuPPR is defined as the time required until a patient reports multiple sequential mild pain scores (r4/10). Any interruption in this sequence suggests a temporary improvement in pain management rather than a durably effective pain management plan. SuPPR is based on the supposition that although prediction and absolute prevention of postoperative pain may not be feasible for all patients, effective postoperative pain management is both desirable and achievable for a large proportion of surgical patients. The primary aim was to examine the amount of time required for patients to achieve multiple consecutive mild pain scores after surgery. Investigators hypothesized that SuPPR could be defined by longer time intervals for patients to report the first of two, three, four, or five consecutive mild pain scores (r4/10). The secondary aim was to compare differences in the time to SuPPR according to age, sex, and type of surgery. They hypothesized that younger age and female gender would be associated with longer time to achieving SuPPR, and that no differences would be observed according to surgery type. Surgical case data were obtained from the University of Florida’s Integrated Data Repository.

When compared with the older group (those 64 years of age and older), the times to the first mild pain rating and consecutive mild pain ratings were significantly longer among younger (21 to 39 years old) and middle-aged (40 to 64 years) groups. Similarly, the time to report mild pain ratings was longer in women than men across all outcome measures. Only musculoskeletal surgery led to decreased times to event; all other types of surgery (such as digestive surgery) were associated with no difference or increased times to SuPPR-1. Patients with numerous comorbidities experienced longer times to event, as did those with more complex types of surgical procedures as indicated by a higher number of current procedure terminology codes. In all cases, the time to event was longest for patients undergoing integumentary, digestive, and urinary types of surgery. The largest incremental increase in time to multiple consecutive mild pain scores was observed between SuPPR-2 and SuPPR-3. Differences also were observed in several factors related to surgery and patients (e.g., age and sex).

These results can be expanded upon to offer probabilistic expectations to patients regarding their time to SuPPR following surgery. This information may at some point prove useful in the development and implementation of hospital-level metrics for postoperative pain management. This study identifies an important period during which patients require more aggressive postoperative pain control, and this period may differ substantially based upon a host of clinical and sociodemographic factors. This time period may warrant increased attention in association with the transition from intermittent to sustained analgesic responses, which may carry important implications for patient safety during analgesic titration considering that this time period has been associated with a greater likelihood of postoperative, opioid-induced respiratory depression.