May 2017
David Craig, PharmD | Editor


The Journal of Pain Summaries 

Highlights from The Journal of Pain (Volume 8, No. 5, May 2017 Issue)

Panel Develops New Diagnostic Criteria for Chronic Sickle Cell Disease

The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks—American Pain Society Taxonomy working group developed core diagnostic criteria for chronic pain associated with sickle cell disease (SCD). 

There are no existing consensus-based criteria for chronic SCD pain for formal diagnostic classification. The lack of clarity in what defines SCD pain has hindered research efforts in understanding the epidemiology of chronic SCD pain and in developing effective pain management interventions in this population.

The recommended core criteria for pain associated with sickle cell disease are:

  1. Diagnosis of SCD confirmed by laboratory testing
  2. Reports of ongoing pain present on most present on most days over the past six months in single or multiple locations
  3. Patients must display at least one sign:
    1. Palpation of the region of reported pain elicits focal pain or tenderness
    2. Movement of the region of reported pain elicits focal pain
    3. Decreased range of motion or weakness in the region of reported pain
    4. Evidence of skin ulcer in the region of reported pain
    5. Evidence of hepatobiliary or splenic imaging abnormalities
    6. Evidence of imaging abnormalities consistent with bone infarction or avascular necrosis in the region of reported pain
  4.  There is no other diagnosis that better explains the signs and symptoms.

The panel also proposed three diagnostic modifiers to indicate subtypes of chronic SCD pain:

  1. Chronic SCD Pain without Contributory Disease Complications: Used if no evidence of contributory SCD complications on the basis of clinical signs or test results
  2. Chronic SCD Pain with Contributory Disease Complications: Should be used if there is evidence of contributory SCD Complications on the basis of clinical signs or test results.
  3. Chronic SCD Pain with Mixed Pain Types:  Should be used if there is evidence of contributory complications, such as avascular necrosis, on the basis of clinical signs or test results, and pain also occurs in unrelated sites (arms, back, chest, abdomen).

Appropriate use of the new criteria is intended for evaluating chronic pain symptoms among persons with SCD and is not appropriate for classifying persons presenting in the emergency department for management of acute vaso-occlusive pain. 

Source: Carlton Dampier, et al, multiple centers, “AAPT Diagnostic Criteria for Chronic Sickle Cell Disease Pain”

Patient Characteristics Can Influence Opioid Therapy

Researchers at Weill Cornel University reviewed patient registry data for 1,159 chronic pain patients.  Seventy-seven percent were treated with opioids. 

The Weil Cornell registry is multisite and uses hospital-based electronic health records to merge demographic and other data with patient-reported outcomes. The researchers sought to evaluate the association of patient characteristics with better or worse treatment outcomes with or without and generalize about best pain management practices.

For example, regression analysis showed that being male predicted a 60 percent greater likelihood of using an opioid than for a female patient. However, gender did not predict the likelihood for higher doses of opioids.

Registry outcomes identified characteristics of subpopulations of chronic pain patients for whom opioids are deemed effective, versus subpopulations who do not significantly benefit from long-term treatment. The data can enable clinicians to evaluate treatment results in a broader context of clinic-level population management.

Lisa, R. Witkin, et al, Weil Cornel Medical College, New York, “Patient-Reported Outcomes and Opioid Use in Outpatients with Chronic Pain”


Highlights from PAIN (Volume 158, No. 5, May 2017 Issue)

Pain Medicine Cover

Does Expecting More Pain Make It More Intense? Factors Associated With the First Week Pain Trajectories After Breast Cancer Surgery

Reetta M. Sipila, Lassi Haasio, Tuomo J. Meretoja, Samuli Ripatti, Ann-Mari Estlander, and Eija A. Kalso; Division of Pain Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Finland; Breast Surgery Unit, Comprehensive Cancer Center, University of Helsinki and Helsinki University Hospital; Institute for Molecular Medicine Finland (FIMM), University of Helsinki; Department of Public Health, Hjelt Institute, University of Helsinki

Pain expectation affects the intensity of acute pain, and expectations can lead to both psychological and physiological responses among patients. In addition, the expectation of high-intensity pain may lead to heightened attention and awareness about pain because of its natural threat value.

The aim of this study was to describe pain trajectories involving the intercept and slope of a linear trend for pain intensities recorded during the first postoperative week after breast cancer surgery and to identify factors associated with acute pain trajectories. Investigators also studied the association of pain expectation with both clinical and experimental pain variables. The aim was to evaluate whether patients with high pain expectations are more sensitive to pain stimulation in general. The main hypothesis was that expecting more severe postoperative pain and having high preoperative distress would have a significant impact on acute postoperative pain trajectories.

This prospective study included 563 women who were treated for breast cancer. Psychological data included responses from questionnaires for depressive symptoms and anxiety. Experimental pain tests for heat and cold were performed before surgery and the amount of oxycodone needed for satisfactory pain relief after surgery was recorded. Pain intensity in the area of operation before surgery and during the first postoperative week and expected intensity of postoperative pain were recorded using the Numerical Rating Scale. Results supported the main hypotheses: expectations of higher postoperative pain and high preoperative distress contributed to more intense postoperative pain (intercept) after breast cancer surgery. Other variables affecting more intense postoperative pain included type of surgery (axillary clearance), preoperative pain in the area of the operation, and the amount of oxycodone needed to obtain the first state of adequate pain relief. Factors associated with a more rapid pain resolution were higher BMI, higher pain expectations, and a higher amount of oxycodone needed.

Acute pain after breast cancer surgery is a multidimensional problem. Psychological distress, pain expectations, and patients’ reports of preoperative pain in the area to be operated on should be recognized and assessed before surgery. Moreover, patients who have axillary clearance need more efficient analgesic approaches. Clinicians need to be knowledgeable about these risk factors and take measures to minimize their influence.

These results merit further study regarding whether genetic factors or previous adverse experiences can explain some of these associations.

Predictors of the Transition From Acute to Persistent Musculoskeletal Pain in Children and Adolescents: A Prospective Study

Amy Lewandowski Holley, Anna C. Wilson, and Tonya M. Palermo; Department of Pediatrics, Institute on Development and Disability, Oregon Health & Science University, Portland; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle

Persistent pain during childhood is associated with limitations in physical functioning, impaired quality of life (QOL), sleep disturbances, peer difficulties, and elevated depressive symptoms. Chronic pain during childhood confers the risk for pain and high healthcare use in adulthood, with the onset of pain in childhood often leading to widespread pain, higher anxiety, and poorer functional status later in life. High prevalence of musculoskeletal (MSK) pain during childhood places a significant burden on children, families, and the healthcare system. Epidemiologic studies suggest MSK pain remits; however, approximately 30% of patients experience continued pain at 1- and 4-year follow-ups.

Investigators hypothesized that at least 30% of youth would endorse persistent MSK pain at 4-month follow-up and that sleep quality, depression, pain anxiety, and conditioned pain modulation (CPM) during the acute pain period would influence pain persistence and pain-related functioning (pain-related disability and QOL) at 4 months. Findings revealed that approximately 35% of youth had persistent pain at 4-month follow-up, with persistence association with poorer CPM and female gender. Depressive symptoms during the acute pain period also served as an important predictor of pain-related disability and QOL at 4 months. Two biopsychosocial factors, female gender and impairment in inhibitory pain modulation, helped to predict the transition from acute to chronic MSK pain. Conditioned pain modulation during the acute pain period influenced both MSK pain persistence and limitations at 4-month follow-up, suggesting that impairment in inhibitory pain modulation may influence children’s nonrecovery from acute MSK pain. This finding extends adult research implicating CPM scores as risk factors for chronic pain and suggests that CPM may be a mechanism in the transition from acute to chronic MSK pain in youth. Targeted interventions or closer monitoring of youth with elevated symptoms at the time of injury should be considered.

Future studies examining the transition from acute to chronic pain should monitor symptoms more frequently to capture potential gender differences in trajectories of pain, mood, and disability over time. Future research also can examine the ways in which age and stage of cognitive development may influence associations between catastrophizing and pain outcomes in youth with acute pain.

The Clinical Journal of Pain

Highlights from The Clinical Journal of Pain (Volume 33, No. 5, May 2017 Issue)


The Mediating Effects of the Different Dimensions of Pain Catastrophizing on Outcomes in an Interdisciplinary Pain Rehabilitation Program

Wesley P. Gilliam, Julia R. Craner, Eleshia J. Morrison, and Jeannie A. Sperry; Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minn

People who catastrophize about pain may interpret pain as an indication of serious and lasting harm. Pain sensations can activate negative beliefs about pain, including its consequences and one’s perceived coping ability.

The Pain Catastrophizing Scale (PCS), one of the most-used measures of pain catastrophizing, captures multiple dimensions of catastrophizing including the tendency to feel helpless in response to pain, perseverate on pain, and exaggerate the threat value of pain. The purpose of this study was to examine the extent to which the three dimensions of pain catastrophizing (ie, helplessness, rumination, and magnification) respond to an intensive, interdisciplinary pain rehabilitation treatment approach. The second purpose was to utilize within-subjects mediation analyses to explore the relative contributions of change in the 3 dimensions of pain catastrophizing on improvements on pain treatment outcomes. Outcomes of interest were pain severity, pain interference, physical quality of life (QOL), mental health QOL, and depressive symptoms.

Results demonstrated that participants showed significant pretreatment-to-posttreatment improvements on the subscales of pain catastrophizing and on all measures of pain adjustment and depressive symptoms. In addition, results of mediation analysis revealed that pretreatment-to-posttreatment improvement in helplessness was the most consistent mediator of outcomes among the PCS dimensions, partially mediating improvements in all treatment outcomes examined beyond the effects of the other mediators tested in the models. When mediating the relationship between treatment and posttreatment pain interference, mental health–related QOL, and depressive symptoms, there were no significant differences between the relative effects of helplessness and pain intensity.

These findings underscore the influence of helplessness as an important construct. Pretreatment-to-posttreatment reductions in the tendency to ruminate about pain partially mediated improvements in pain severity, interference, and depression beyond the effect of the other mediators in the model (helplessness, magnification, and pain severity). These results suggest that change in two dimensions of catastrophizing—the tendency to feel helpless and perseverate in the face of pain—had the greatest impact on outcomes among treatment-seeking participants. Rehabilitative approaches that embody cognitive behavioral therapy approaches and integrate functional restoration modalities may be particularly well suited to address these dimensions of catastrophizing. Pain rehabilitation treatments that deemphasize pain severity and emphasize active approaches to self-management of pain and disability may enhance self-efficacy to manage pain and function, decrease healthcare use, and reduce feelings of helplessness and the tendency to ruminate over failed pain management approaches. Continued research should explore the ways in which change in the dimensions of pain catastrophizing influences outcomes from interdisciplinary pain treatment approaches.

Trends in the Nonmedical Use of OxyContin, United States, 2006 to 2013

Christopher M. Jones, Pradip K. Muhuri, and Peter G. Lurie; The US Department of Health and Human Services, Washington, DC; Agency for Healthcare Research and Quality, Rockville, Md.; US Food and Drug Administration, Silver Spring, Md

Most nonmedical use of OxyContin occurs through oral ingestion, but some nonmedical use of OxyContin involves modifying the extended-release product to create a powder, liquid, or vapor, making it suitable for nonoral routes such as inhalation, injection, and smoking. Although nonmedical use of opioids by any route poses significant risks, nonoral routes have been identified as conveying a particularly high risk for overdose. In an effort to deter the nonmedical use of OxyContin, primarily through nonoral routes, the manufacturer, Purdue Pharma, reformulated the product to make it more difficult to break, crush, and dissolve, and in April 2010, the US Food and Drug Administration approved the reformulated product. However, no studies have found that reformulated OxyContin meaningfully reduces oral abuse or has any impact on the development of opioid use disorders.

This study attempted to address the limitations of previous epidemiological studies by assessing nonmedical use of OxyContin among a nationally representative population and a subset of past-year nonmedical users of pain relievers to account for secular trends in overall nonmedical use of prescription pain relievers and examining nonmedical use of OxyContin over an 8-year period from 2006 through 2013.

Findings demonstrate a statistically significant decline in the prevalence of nonmedical use of OxyContin in the United States in 2013 compared with 2010. This equates to an estimated 437,000 fewer individuals reporting nonmedical use of OxyContin in 2013 compared with 2010—a 23.3% decline. But this study also revealed persistent nonmedical use of OxyContin among people reporting past-year nonmedical use of pain relievers. With few exceptions, the prevalence of past-year nonmedical use of OxyContin among nonmedical users of pain relievers in 2013, 3 years after the introduction of a formulation designed to deter abuse, was significantly higher than or similar to historical prevalence rates before reformulation. The findings also indicate no significant reductions in nonmedical use of OxyContin after reformulation in high-risk groups such as those reporting 200 days or more of past-year nonmedical use of pain relievers and those with pain reliever abuse or dependence. These findings raise important questions about the continued nonmedical use of OxyContin, especially among high-risk populations.

Stakeholders engaged in product development must continue to develop better technologies that thwart all routes of abuse. These efforts must be coupled with broader efforts targeted at the underlying drivers of opioid abuse—inappropriate prescribing of and overreliance on prescription opioids for pain management and untreated opioid use disorders.