December 2016
David Craig, PharmD | Editor


The Journal of Pain

Highlights from The Journal of Pain (Volume 17, No. 12, December 2016 Issue)

Journal of Pain cover

Study Explores Impact of Lifetime Trauma on Pain Severity

Andrea L. Nicol, Christine B. Sieberg, Daniel J. Clauw, Afton L. Hassett, Stephanie E. Moser, Chad M. Brummett; Department of Anesthesiology, University of Kansas School of Medicine, Kansas City, KS; Division of Pain Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, and Biobehavioral Pediatric Pain Lab, Boston Children's Hospital; Department of Psychiatry, Harvard Medical School, Boston, MA; Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI

Do people with histories of sexual and physical trauma experience worse pain severity and functional impairment? A multicenter research team writing in The Journal of Pain hypothesized that patients with a history of lifetime trauma would present a worse clinical phenotype and report higher levels of negative affect, greater pain severity, and reduced physical functioning, even when controlling for the presence of fibromyalgia.

Data for the study was sourced from a clinical care and research initiative at the University of Michigan Back and Pain Center. All new patients were given questionnaires about medical comorbidities and multiple self-validated measures of pain, mood, and function. The sample included 3,081 individuals with chronic pain.

Previous studies have shown an association of sexual and physical trauma with abdominal pain, pelvic pain, musculoskeletal pain, and fibromyalgia, and 28%–71% of fibromyalgia patients report a history of abuse. Greater understanding of the patterns of chronic pain in survivors of abuse and trauma is important for appropriate clinical assessment and intervention.

Results of the study showed that 15% of the subjects reported a history of abuse. Compared to patients with chronic pain without a history of abuse, they had greater depression and anxiety, worse physical functioning, greater pain severity, worse pain interference, higher catastrophizing, and higher scores on the Fibromyalgia Survey Criteria.

The authors concluded that the dynamic interplay of the psychological and physical variables has a more significant effect on severity of pain and worsening of physical function than the effect of any single variable.

French Study Reports Codeine Shopping Prevalence in Chronic Pain Patients

Chouki Chenaf, Jean-Luc Kabore, Jessica Delorme, Bruno Pereira, Aurélien Mulliez, Lucie Roche, Alain Eschalier, Noémie Delage, Nicolas Authier; INSERM, UMR 1107 NEURO-DOL, Faculté de Médecine, Université d’Auvergne, Clermont-Ferrand, France; CHU Clermont-Ferrand, Centres Addictovigilance et Pharmacovigilance Auvergne (CEIP-CRPV), Service de Pharmacologie Médicale, Clermont-Ferrand, France

Codeine is the most commonly used opioid analgesic in the world and, in recent years, reports of codeine misuse have increased, especially in countries where it is available over the counter, such as Australia, New Zealand, France, and the United Kingdom. In France, codeine is the top selling opioid analgesic and is used in combination with paracetamol to relieve mild to moderate pain.

Although codeine is a widely used analgesic and the potential for abuse is significant, no prospective studies have been published to assess the magnitude of its misuse potential. A multicenter French research team assessed the incidence of codeine shopping for 1 year in a cohort of individuals with chronic noncancer pain. They performed a retrospective analysis of data from a French health insurance database. A total of 1,958 patients in the database were treated with codeine for 6 consecutive months.

For the study, codeine shopping behavior was defined as at least 1 day of overlapping prescriptions from two or more prescribers that were filled in three or more pharmacies.

Results showed that codeine shopping occurred in 4% of the chronic noncancer pain patients. Risk factors associated with codeine shopping were younger age (≤40 years old), presence of a mental health disorder, concurrent use of benzodiazepines, and previous use of opioids. The study did not find a significant association between alcohol abuse and codeine shopping.


Highlights from PAIN (Volume 157, No. 12, December 2016 Issue)

Pain Medicine Cover

Open-Label Placebo Treatment in Chronic Low Back Pain: A Randomized, Controlled Trial

Claudia Carvalho, Joaquim Machado Caetano, Lidia Cunha, Paula Rebouta, Ted J. Kaptchuk, Irving Kirsch; ISPA—Instituto Universitário de Ciências Psicológicas, Sociais e da Vida, Department of Clinical and Health Psychology, Lisbon, Portugal; Nova Medical School—Faculdade de CinciasMedicas, da Universidade Nova de Lisboa, Lisbon, Portugal; Unidade de Terapia de Dor do Hospital de Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal; Program in Placebo Studies, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

Studies have demonstrated that some commonly prescribed front-line therapies for low back pain (LBP) are not superior to placebo controls in double-blind, randomized clinical trials or only are of marginal increased efficacy. Placebo responses in trials for LBP can be large and clinically significant.

Administering fake pills to harness placebo effects poses an ethical conundrum for physicians in clinical practice. However, four studies have tested the effect of an open-label placebo (OLP) prescription, and all data indicate that patients report benefits after taking pills presented honestly as placebos.

The goal of this study was to investigate whether adding OLP to treatment as usual (TAU) can benefit patients with chronic LBP (cLBP) when compared to TAU that controlled for additional spontaneous improvement, regression to the mean, and the patient-provider relationships. Pain severity was assessed on three 0- to 10-point numeric rating scales scoring maximum pain, minimum pain, and usual pain and a composite primary outcome total pain score. The other primary outcome was back-related dysfunction, assessed on the Roland-Morris Disability Questionnaire. In an exploratory follow-up, participants on TAU received placebo pills for 3 additional weeks. Investigators randomized 97 adults reporting persistent LBP for more than 3 months (pain was diagnosed by a board-certified pain specialist), and 83 adults completed the trial.

Investigators found that adding OLP to TAU resulted in significantly better reductions in cLBP and pain-related disability than TAU alone. The amount of additional pain reduction produced by OLP was approximately 30% of baseline pain and disability ratings. Almost 90% of the participants in this trial were taking pain medication, primarily NSAIDs, before and during the trial. Although NSAIDs are reported to reduce LBP more than a double-blind placebo, the difference amounts to less than 1 point on a 0 to 10 pain scale. In this study, OLP enhanced pain reduction by 1.49 points on a 0 to 10 scale compared to a 0.24-point change with continued standard treatment without the added placebo. This was an added benefit beyond the effect of continued NSAIDs and/or other ongoing treatment. These data suggest that patients with cLBP can benefit from the addition of OLP to their current treatment regimen and that OLP can be a safe and effective adjunct to treatment for cLBP. Seventeen participants requested prescriptions for a placebo at the end of their study participation. Harnessing placebo effects without deception is possible in the context of a plausible rationale. More research on this possibility is warranted in cLBP and other conditions defined by self-appraisal.

Survey of Herbal Cannabis (Marijuana) Use in Rheumatology Clinic Attendees with a Rheumatologist Confirmed Diagnosis

Peter A. Ste-Marie, Yoram Shir, Emmanouil Rampakakis, John S. Sampalis, Angela Karellis, Martin Cohen, Michael Starr, Mark A. Ware, Mary-Ann Fitzcharles; Alan Edwards Pain Management Unit, McGill University Health Centre, Montreal, Canada; JSS Medical Research, St-Laurent, Quebec, Canada; Jewish General Hospital, McGill University, Montreal, Canada; Division of Rheumatology, McGill University Health Centre, Montreal, Canada

Herbal cannabis (marijuana) has gained widespread popularity and acceptance as an effective treatment for many ailments with pain a commonly cited complaint. To date, there remains a lack of sound study on the effects of medicinal marijuana use for many conditions. Most epidemiological studies examining medicinal marijuana use have been based on self-reported diagnosis of a medical condition. The objective of this study was to document the self-reported prevalence of medicinal marijuana use among 1,000 patients with an accurate rheumatologist diagnosis and physician assessment of rheumatic condition severity.

Few participants (4.3%) self-reported past or present use of medicinal marijuana. Compared with nonusers, current users reported poorer health status, more pain and disease severity, more opioid use, and were less likely to be employed. Almost 80% of medicinal marijuana users were satisfied with the benefits of marijuana to relieve pain, decrease anxiety and nausea, and promote sleep. Previous recreational marijuana use was reported by more than 80% of current medicinal users, with more than one-third reporting concurrent medicinal and recreational use. The limited use of medicinal marijuana by patients with rheumatic conditions was surprising, especially in a climate of public advocacy for use. Older age and lifetime discontinuation of cigarette smoking (strongly encouraged by rheumatologists) may have contributed to these low numbers. Medicinal marijuana users self-reported more severe disease and symptoms than nonusers by validated measures of disease status for rheumatic diseases. Physicians assessed that 9.6% of the entire study population had severe disease, whereas 25.4% of patients rated their disease as severe. This disparity between physician and patient assessment was especially present for marijuana users, with physician global assessment and patient global assessment rated as severe for 10.7% and 46.4% of patients, respectively. Discrepancies between patients’ and health professionals’ assessments are well known for conditions such as procedure pain and cancer pain. Two possible explanations for user discrepancies may be that herbal cannabis itself, rather than the rheumatic disease, was associated with negative outcomes or that cannabis users were truly sick and in need of extra measures to reduce pain and other disease symptoms.

The low rate of medicinal marijuana use by current rheumatology respondents challenges the reliability of reports of musculoskeletal complaints and especially “severe arthritis” as justification for medical marijuana use. Although marijuana may be used for legitimate medical purposes by patients with more severe rheumatic diseases, it also is possible that this disease label is used by some to inappropriately access marijuana. Marijuana is not an innocuous substance, and its use has implications for both patient and societal safety. More controlled studies are required to determine the role of marijuana in the treatment of rheumatic conditions before use recommendations are distributed to the medical community.

The Clinical Journal of Pain

Highlights from The Clinical Journal of Pain (Volume 32, No. 12, December 2016 Issue)


Multiple Levels of Suffering: Discrimination in Healthcare Settings Is Associated with Enhanced Laboratory Pain Sensitivity in Sickle Cell Disease

Vani A. Mathur, Kasey B. Kiley, Carlton Haywood, Jr., Shawn M. Bediako, Sophie Lanzkron, C. Patrick Carroll, Luis F. Buenaver, Megan Pejsa, Robert R. Edwards, Jennifer A. Haythornthwaite, and Claudia M. Campbell; Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD; Texas A & M University, Department of Psychology, College Station, TX; Johns Hopkins University School of Medicine, Division of Hematology; University of Maryland, Baltimore County, Department of Psychology, Baltimore, MD; Harvard Medical School, Departments of Anesthesiology, Perioperative, Pain Medicine, and Psychiatry; Brigham and Women’s Hospital, Pain Management Center, Harvard Medical School, Chestnut Hill, MA

Patients with sickle-cell disease (SCD) often are perceived as “difficult patients” and may be disproportionately exposed to biased and discriminatory treatment in healthcare settings. Despite the availability of SCD pain treatment guidelines, patients with SCD report undertreatment of pain and poor interpersonal treatment in healthcare settings. Also, patients with SCD often are perceived as drug seekers or addicts and might display behaviors during interactions with providers that are misperceived as being characteristic of substance abuse. Discrimination in healthcare settings may directly affect multiple health outcomes, including pain management, clinical pain, and pain sensitivity.

These investigators examined the relationship between perceived racial discrimination within healthcare settings and clinical pain and laboratory pain sensitivity among adults with SCD. They used tests of central sensitization (e.g., temporal summation) as a possible mechanism and marker of pain chronification and hypothesized that discrimination would be associated with increased clinical pain and facilitation of laboratory pain.

Seventy-one patients with SCD provided self-reports of experiences with discrimination in healthcare settings and clinical pain severity and completed a psychophysical pain testing battery in the laboratory. When compared with patients who report no discrimination within healthcare settings, those who experience discrimination have a profile that includes heightened clinical pain severity and sensitivity to suprathreshold thermal stimuli, increased after-sensations, and greater mechanical temporal summation of pain. Although discrimination did not remain significantly associated with clinical pain severity when other pain-related covariates were included in the multivariate models, discrimination was independently associated with acute pain processing in the laboratory, particularly measures of pain facilitation. Healthcare discrimination also was associated with a variety of symptoms of distress, including more depressive symptomatology, poorer sleep, and higher stress ratings.

These findings are consistent with literature that demonstrates positive associations between lifetime discrimination and pain, stress, depression, and poor sleep. Discrimination among African American adults also is associated with delays in seeking medical care and lower adherence to doctor recommendations. These results indicate that measures of discrimination should be included in future studies of pain sensitivity in SCD and more broadly suggest that interpersonal experiences may influence physiological processes underlying pain processing and central sensitization. Future research should examine weather intervening at the level of interpersonal interactions may potentially lessen some of the deleterious effects of discrimination.

The Association Between Chronic Pain and Cardiac Disease: A Cross-Sectional Population Study

Alan Fayaz, Hilary C. Watt, Richard M. Langford, and Liam J. Donaldson; Department of Surgery and Cancer, Imperial College London; Department of Pain and Anaesthesia, Barts Health NHS Trust, London

Numerous authors have sought to validate a causal relationship between chronic pain and cardiovascular disease. Claims that risk for cardiovascular disease is proportional to the duration, severity, or distribution of chronic pain need to be balanced against the understanding that previous studies were based on observational data with little consistency in the terminology used to define pain symptoms and cardiovascular indices. The ability to establish causality also has been hampered by the failure to comprehensively address potentially confounding variables, in particular the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) that have well-publicized effects on cardiovascular health. This study used national data, collected as part of the Health Survey for England, to explore the hypothesis that chronic pain is independently associated with cardiac disease and this augmented risk is proportional to the intensity of pain symptoms. Investigators applied logistic regression analysis to data from 8,596 adults surveyed in a study of the health of the population of England. The association between cardiac disease (angina and/or myocardial infarction) and chronic pain (pain lasting more than 3 months) was explored, taking account of 10 potentially confounding variables, including the regular use of NSAIDs.

After adjustment for confounding variables, investigators demonstrated that participants reporting chronic pain symptoms were 55% more likely to experience cardiac disease than those not reporting chronic pain. Three indices were used to describe pain intensity: chronic pain distribution, chronic pain disability, and average chronic pain score. Data indicate that cardiac risk increases markedly in line with chronic pain intensity regardless of the measure used.

These results are consistent with published studies citing statistically significant increases in cardiovascular morbidity, ranging from 18% to 83%, that are most pronounced in populations with high-intensity chronic pain. However, in previous studies, confounding variables were not comprehensively accounted for in the statistical models used. This study adjusts for a wide range of potentially confounding cardiovascular risk factors including age, sex, socioeconomic status, body mass index, diabetes, hypertension, smoking, anxiety, depression, and regular use of NSAIDs. Regular use of NSAIDs was independently associated with both chronic pain and cardiac disease; however, it was not a statistical confounder in the association between chronic pain and cardiac disease. Although it would be simplistic to surmise that cardiac risk attributable to regular use of NSAIDs can be explained entirely by coexisting chronic pain, these data highlight the complex interplay between these three factors in clinical practice and reaffirm the need to carefully balance overall cardiac risk against the potential analgesic benefits NSAIDs can provide. Future work needs to address the possibility of modifying the impact of chronic pain on cardiovascular morbidity and mortality through improved pain control and reduction of symptom intensity.