October 2017
David Craig, PharmD | Editor


The Journal of Pain

Highlights from The Journal of Pain (Volume 18, No. 10, October 2017 Issue)

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Study Evaluates Inpatient Opioid Use in Children with Pain

Gary A. Walco, Nancy Gove, Jennifer Phillips, Steven J. Weisman; Department of Anesthesiology and Pain Medicine, University of Washington School of Medicine, Seattle, Washington; Seattle Children's Hospital, Seattle, Washington; Seattle Children's Research Institute, Seattle, Washington; Departments of Anesthesiology and Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin; Children's Hospital of Wisconsin, Milwaukee, Wisconsin

“The FDA should be absolutely ashamed of itself for this reckless act,” wrote Sen. Joe Manchin (D-W.Va.) in a letter to the agency protesting approval of an extended release of oxycodone medication to treat chronic pain in children 11 to 16 years old. The FDA responded and highlighted the need for balancing individual pain control against public health concerns about opioid misuse.

According to pediatric pain experts writing in The Journal of Pain, two overriding issues are confronting pediatric pain medicine:

  • Most pain medications on the market are prescribed to children off label because specific indications have not been validated for safety and efficacy in children.
  • There is a compelling need for systemic clinical trials to study use of opioids to treat moderate to severe pain in children.

Researchers from Seattle Children’s Hospital and Children’s Hospital of Wisconsin addressed the serious lack of knowledge regarding pain medication practices among pediatric inpatients. The study aimed to fill the gaps in our knowledge regarding potential opioid misuse in pediatric populations by surveying medical records of admissions to a major children’s hospital over a 12-month time span.

Researchers examined data extracted from medical records at Seattle Children’s Hospital and focused on encounters, or single admissions regardless of length, in which any opioid medication on the hospital formulary was administered. Opioid use related to surgery was excluded.

For the year examined, 11,365 encounters were reviewed, representing 8,179 unique patients. Of those, 44% (3,559 patients) received opioid therapy. For all administrations, three in four encounters involved opioid use for up to 5 days. Overall, many patients who received opioids for a more extended period of time were treated in critical care settings, and it was unknown if opioids were used to address pain or treat other complications.

Based on their findings, the authors noted that hospitalized children are prescribed opioids primarily for acute care, and long-term use appears to be restricted for children with cancer and those undergoing extensive cardiac and medical care. Although administration of opioids is common for treating pediatric inpatients with acute pain, there is little evidence showing that opioids are widely used for chronic pain problems among pediatric inpatients. Therefore, because opioid administration is rare for extended periods of time in children, the authors concluded that inpatient use of these medications is not a major factor contributing to opioid misuse nationwide.


Highlights from PAIN (Volume 158, No. 10, October 2017 Issue)

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Disrupted Offset Analgesia Distinguishes Patients with Chronic Pain from Healthy Controls

Hiroyuki Kobinata, Eri Ikeda, Shuo Zhang, Tianjiao Li, Koshi Makita, Jiro Kurata; Department of Anesthesiology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan; Department of Anesthesiology and Pain Clinic, Hospital of Medicine, Tokyo Medical and Dental University, Tokyo

Offset analgesia (OA) is a phenomenon in which a disproportionately large decrease in pain sensation occurs after a brief, temporary increment of thermal pain stimulus by 1°C. Offset analgesia has been reported as absent or decreased in patients with neuropathic pain versus healthy control subjects. Although the exact neural mechanisms of such alteration of OA have yet to be determined, one possible explanation for this phenomenon might be an attenuated descending pain modulatory system in chronic pain states.

The aim of this study was to investigate the relationships among altered OA responses, various psychophysical properties, and varied OA stimulus durations in patients with chronic pain in comparison to profile-matched healthy controls. First, investigators examined pain responses to control tonic and OA paradigms in a number of healthy volunteers to confirm the effects of age, sex, and varied stimulus durations of OA. Second, they compared pain responses to the same stimulus paradigms between patients with chronic pain and age- and sex-matched healthy control subjects. Third, they explored the possibility of distinguishing patients with chronic pain from healthy controls using parameters derived from the pain responses. Investigators hypothesized that (1) the extent of OA alteration might be associated with morbidity of chronic pain as characterized by pain intensity, pain duration, and several parameters derived from various psychophysical questionnaires; (2) the extent of OA alteration might be associated with temporal elements of pain stimulation; and (3) the magnitude of OA or its related parameters might distinguish patients with chronic pain from healthy controls in a similar manner to that reported in neuropathic pain.

Investigators showed that OA was attenuated in patients with chronic pain from various etiologies in comparison with healthy controls. Findings also demonstrated longer T2-enhanced OA magnitude in patients with chronic pain and healthy controls. Although patients had OA responses more similar to those of healthy controls with longer T2, they required 15-second T2 to reach an OA response similar to that of healthy subjects. Investigators contend that OA requires sufficient temporal summation of pain by thermal stimulus before offset and that patients with chronic pain require a longer duration of noxious stimulus because of delayed temporal summation of pain. Because all subjects were Japanese, lower tolerability to pain stimulation might be explained by an ethnic difference in which Asians showed higher sensitivity to suprathreshold pain stimulation than non-Hispanic whites.

The fact that OA is enhanced by a longer duration of pain stimulation implies possible involvement of central sensitization in exerting the endogenous pain modulatory system. Delayed pain perception in patients with chronic pain might be a contributing factor to endogenous pain modulatory activity, which underlies the mechanisms of pain chronification. Investigators suggest that the OA index might be a useful marker with which to distinguish patients with chronic pain from healthy controls.

Brain Signature and Functional Impact of Centralized Pain: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Network Study

Jason J. Kutch, Eric Ichesco, Johnson P. Hampson, Jennifer S. Labus, Melissa A. Farmer, Katherine T. Martucci, Timothy J. Ness, Georg Deutsch, A. Vania Apkarian, Sean C. Mackey, David J. Klumpp, Anthony J. Schaeffer, Larissa V. Rodriguez, Karl J. Kreder, Dedra Buchwald, Gerald L. Andriole, H. Henry Lai, Chris Mullins, John W. Kusek, J. Richard Landis, Emeran A. Mayer, J. Quentin Clemens, Daniel J. Clauw, Richard E. Harris, for the MAPP Research Network; Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles; Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan, Ann Arbor; Oppenheimer Center for Neurobiology of Stress, Pain and Interoception Network (PAIN), David Geffen School of Medicine at UCLA, Los Angeles; Department of Physiology, Northwestern University, Feinberg School of Medicine, Chicago; Department of Anesthesiology, Perioperative and Pain Medicine, Division of Pain Medicine, Stanford University Medical Center, Stanford; Departments of Radiology and Anesthesiology, University of Alabama, Birmingham Medical Center, Birmingham; Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago; Department of Urology, University of Southern California, Los Angeles; Department of Urology, University of Iowa, Iowa City; College of Medicine, Washington State University, Seattle; Department of Urology, Washington University, Saint Louis; National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia; Department of Urology, University of Michigan, Ann Arbor

Urologic chronic pelvic pain syndrome (UCPPS) is a highly prevalent but poorly understood chronic pain condition. It encompasses interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. Despite the clinical presentation of UCPPS, which primarily is characterized by chronic and often debilitating pain in the pelvic region, no generally effective treatments have been identified. The lack of generally effective treatments may be related to unidentified heterogeneities within the UCPPS population. To identify underlying pathological pain factors that may be related to widespread pain in some patients with UCPPS, investigators designed a study to address three hypotheses: (1) patients with UCPPS would display a reliable distribution of widespread pain, with some patients reporting highly localized pain in the pelvic region and others reporting additional pain in other body locations as in fibromyalgia, (2) patients with UCPPS reporting pain at more body locations would have lower measures of physical and mental function even after controlling for overall pain severity, and (3) patients with UCPPS reporting widespread pain would have common neurologic brain alterations independent of clinical diagnoses such as UCPPS and fibromyalgia.

The investigators studied whether centralization manifests at the level of the brain using data from 1,079 participants in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network (MAPP) study. Participants with UCPPS were compared to pain-free controls and patients with fibromyalgia and completed questionnaires capturing pain severity and function. A subset underwent functional and structural magnetic resonance imaging.

Investigators identified patient subtypes within a clinical diagnosis (UCPPS) that expressed differing degrees of widespread body pain. More widespread body pain was associated with reduced daily function independent of pain severity, and pain was associated with a pattern of brain structure and function that also was observed in fibromyalgia, the prototypical centralized pain state. In the future, the identified brain-based outcomes associated with widespread pain can be clinically useful as an objective marker of pain that can help clinicians identify and quantify the amount of the centralized pain dimension within a given individual.

The Clinical Journal of Pain

Highlights from The Clinical Journal of Pain (Volume 33, No. 8, August 2017 Issue)


Smoking Status and Opioid-Related Problems and Concerns Among Men and Women on Chronic Opioid Therapy

Kelly C. Young-Wolff, Daniella Klebaner, Constance Weisner, Michael Von Korff, Cynthia I. Campbell; Division of Research, Kaiser Permanente Northern California, Oakland; Department of Psychiatry, University of California, San Francisco; Group Health Research Institute, Seattle

Smoking is associated with elevated risk of chronic pain, and there is a dose-response relationship between the number of cigarettes smoked per day and the likelihood of experiencing certain types of chronic pain. Smokers report a higher number of painful physical sites, more severe pain intensity, and more functional impairment and long-term disability than nonsmokers. Further, nicotine dependence is associated with more severe pain symptoms. Conversely, chronic pain contributes to smoking maintenance and nicotine dependence. Smoking after nicotine deprivation increases tolerance for pain, whereas nicotine withdrawal is associated with increased pain sensitivity.

Despite the potential short-term pain inhibitory effects of nicotine, chronic exposure to tobacco smoke may sensitize pain receptors and increase pain sensitivity over time. Smokers use more analgesic medications and require higher doses relative to nonsmokers, and they are more likely than nonsmokers to be on long-term opioid therapy for chronic pain. This study examines sex-specific associations between smoking status and patient-reported problems and concerns regarding chronic opioid therapy (COT) among patients prescribed opioids for noncancer chronic pain. Investigators hypothesized that smokers would report a higher number of perceived problems and concerns with COT and that the association between smoking status and perceived problems and concerns with COT would vary by sex.

Findings revealed that current smoking status was associated with opioid use disorders and general substance use disorders among both males and females. Consistent with prior research, current and former male smokers took substantially higher daily doses of prescription opioids than never smokers. However, current smoking was only associated with a large increase in opioid dose among males, suggesting that male smokers are at high risk for problematic opioid use and continue to use much higher doses than their nonsmoking counterparts. Current smoking was not associated with higher pain intensity; perhaps smokers were already prescribed higher doses of opioids to manage increased pain sensitivity attributable to chronic smoking.

The low levels of reported problems with opioids among male current and former versus never smokers—despite elevated opioid doses—are concerning. Whether fewer reported problems with opioids among current and former smokers are attributable to underreporting versus actually perceiving fewer problems with opioids is unclear. Findings highlight current smokers as being at risk for opioid use disorders but less likely to attribute problems to their use of prescription opioids. Clinicians should address the disconnect between provider-defined problems and smokers’ perceptions of opioid-related problems. Additional research is needed to further develop and test efficacious, patient-centered interventions for tobacco smoking that can be integrated into clinical treatment for chronic pain.

A Pilot Comparison of a Smartphone App with or Without 2-Way Messaging Among Chronic Pain Patients: Who Benefits from a Pain App?

Robert N. Jamison, Dylan C. Jurcik, Robert R. Edwards, Chuan-Chin Huang, and Edgar L. Ross; Departments of Anesthesiology, Perioperative and Pain Medicine, Pain Management Center, and Psychiatry, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

Eighty percent of adults worldwide will own a smartphone by 2020. With increased availability of smartphones and Internet accessibility, older adults, those with lower household incomes, and people in both urban and rural environments will have access to sophisticated health-related apps. These programs can offer interventions to more patients than can be seen individually, particularly to patients who require chronic disease management. To date, most apps designed for patients with pain have lacked provider involvement or direct communication of daily assessments. This study’s investigators designed a pain app that summarized patient progress on templated line graphs, tracked behavior, and shared information with healthcare providers by posting the summary data on patients' electronic medical records. They proposed a pilot study to determine the effect of introducing a smartphone pain app for patients with chronic pain that assesses, monitors, and communicates their status to their providers and provides self-management strategies. Investigators hypothesized that (1) patients would find the app easy to use and be adherent in using the app for at least 1 month, (2) the daily assessment ratings from the pain app would be valid and reliable, (3) those who received supportive messaging would be more adherent in using the app, and (4) those who regularly used the app would demonstrate better improvement in pain, mood, and activity. They recruited patients with cancer and noncancer chronic pain to participate in this pilot study.

The following measures were administered to all study participants at baseline, 6-week midpoint, and 3-month follow-up time points: Brief Pain Inventory, Pain Catastrophizing Scale (PCS), Pain Disability Inventory (PDI), Hospital Anxiety and Depression Scale (HADS), and Coping Strategies Questionnaire. Ninety (85.7%) of 105 participants successfully downloaded the pain app program, and 82 (78.1%) of the participants submitted daily reports. Sixty-three of the 80 participants who used the app successfully completed and mailed back satisfaction questionnaires after 3 months. Although compliance of daily ratings tended to decrease after 1 month, participants with more daily assessments were more satisfied with the app than those who used it less often. Those who used the app more frequently demonstrated modestly increased levels of activity (increased steps), but overall frequency of use did not significantly affect pain intensity, mood, coping, or activity level.

Among surveyed physicians, 85.7% believed app use would improve their overall practice, and no physician believed the pain app was an added burden to the clinic. Seventy-one percent of physicians were satisfied with the way pain app data helped them manage their patients, and 71.4% were satisfied with the pain app summary graphs and the way the app helped their patients understand their pain.

Overall, the smartphone pain app was found to be usable, valid, reliable, and easily accepted among patients and providers, although further validity and reliability testing of pain app items should be considered in future investigations. Continued research to understand ways to optimize the use of these applications for clinical use also is needed.