November 2015
David Craig, PharmD | Editor


The Journal of Pain

Journal of Pain cover

The following highlights summarize selected articles from The Journal of Pain (Volume 16, Issue 11, November 2015 Issue).

Manual Physical Therapy Versus Surgery for Carpal Tunnel Syndrome: A Randomized Parallel Group Trial

César Fernández-de-las Peñas, Ricardo Ortega-Santiago, Ana I. de la Llave-Rincón, Almudena Martínez-Perez, Homid Fahandezh-Saddi Díaz, Javier Martínez-Martín, Juan A. Pareja, Maria L. Cuadrado-Pérez; Department of Physical Therapy, Occupational Therapy, Rehabilitation and Physical Medicine, Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain; Department of Neurology and Neurophysiology and Department of Traumatology and Orthopaedic Surgery, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain; Department of Neurology, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain

The results of a randomized clinical trial published in The Journal of Pain showed that for treatment of carpal tunnel syndrome (CTS), surgery and manual physical therapies were similarly effective in improving pain and function.

A team of Spanish researchers conducted a randomized clinical trial to compare the 1-year effectiveness of manual physical therapies, including desensitization maneuvers of the central nervous system, and surgery in patients with CTS. CTS surgery has the highest utilization rate of upper extremity procedures performed.

CTS is a pain disorder in the upper extremity caused by compression of the median nerve at the carpal tunnel. Prevalence in the United States is estimated at 6%–11%, and 6-year cumulative lost income per patient ranges from $45,000 to $89,000. Treatment can be conservative or surgical, but scientific evidence for each therapeutic option is conflicting.

For this study, 120 women with CTS were randomized into two groups: treatment with physical therapy and treatment with surgery. At 12 months, 92% of the study participants completed the follow-up.

The researchers found that patients who had surgery and those treated with physical therapy showed similar outcomes for pain relief and function at 6 months and 12 months. However, patients assigned to physical therapy experienced significantly greater relief of symptoms and improvements in hand function at 1 and 3 months.

Out-Of-Pocket Expenditures on Complementary Health Approaches Associated with Painful Health Conditions in a Nationally Representative Adult Sample

Richard L. Nahin, Barbara J. Stussman, Patricia M. Herman; National Center for Complementary and Integrative Health, National Institutes of Health, Bethesda, MD; RAND Health, RAND Corporation, Santa Monica, CA

Persons with chronic pain conditions often seek relief from complementary health approaches, such as acupuncture, chiropractic care, massage therapy, and herbal remedies. According to research reported in The Journal of Pain, U.S. adults with pain conditions spent $15 billion on complementary practitioners, products, classes, and other materials to treat or manage their pain.

Researchers with the National Center for Complementary and Integrative Health, National Institutes of Health, and RAND Health examined data from 5,467 adults who participated in the 2007 National Health Interview Survey. They sought to estimate aggregate and per-person costs for complementary health approaches associated with 14 different painful health conditions.

Results of the analysis showed that aggregate expenditures for complementary health approaches were $14.9 billion. Total out-of-pocket expenditures for complementary health approaches were highest among individuals with back pain, with a total of $8.7 billion, far surpassing outlays for other pain conditions. Annual condition-specific, per-person costs ranged from $568 for headaches to $895 for fibromyalgia.


Pain Medicine Cover

The following highlights summarize selected articles from PAIN (Volume 156, No 11, November 2015 Issue).

Sleep-Disordered Breathing Decreases After Opioid Withdrawal: Results of a Prospective Controlled Trial

Andreas Schwarzer, Marie Aichinger-Hinterhofer, Christoph Maier, Jan Vollert, Jörg Werner Walther; Departments of Pain Medicine and Internal Medicine, Pneumology, Allergology, and Sleep Medicine; BG-University Hospital Bergmannsheil, Ruhr-University Bochum, Bochum, Germany

The rate of cardiovascular events among elderly patients with arthritis who are treated with opioids and the incidence of strokes among patients with prostate cancer who also are treated with opioids are both on the rise. Sleep-disordered breathing (SDB) often goes clinically unnoticed but constitutes a frequently occurring opioid side effect. Although there are no relevant signals for opioid-associated cardiotoxicity, opioids can cause SDB in as many as 80% of patients who use them by relaxing the upper airways or influencing the central regulation of respiration, which can amplify hypoxia.

For this study, investigators used a dechallenge model with opioid withdrawal as a treatment variable and a nonopioid control group (CG) observed before and after receiving comprehensive pain management. Patients with chronic pain who were long-term opioid users had clinically significant SDB compared to patients who did not take strong-acting opioids. After opioid withdrawal, apnea-hypopnea index (AHI) and central apnea index levels were significantly reduced. The frequency of central apnea was 50% in the opioid withdrawal group; these study findings are in accordance with the reported prevalence of SDB in patients taking opioids. No central sleep apnea was detected in the CG. The significant decrease in the overall AHI after withdrawal was driven mainly by the abolition of central apnea and the highly significant reduction of hypopnea.

Mean oxygen saturation was decreased among chronic opioid users and improved significantly after opioid withdrawal across all sleep stages and during waking. Chronic opioid use should be regarded as an independent risk factor for SDB with central apnea and nocturnal hypoxemia. Before opioid withdrawal, all of the patients exhibited a significantly pronounced daytime sleepiness.

Further studies could investigate the influence of opioid intake on SDB for patients who are beginning new opioid therapies, and on explicit cardiovascular events as a consequence of SDB after long-term opioid use.

Systematic Review of the Face, Legs, Activity, Cry, and Consolability Scale for Assessing Pain in Infants and Children: Is it Reliable, Valid, and Feasible for Use?

Dianne J. Crellin, Denise Harrison, Nick Santamaria, Franz E. Babl; Department of Nursing, The University of Melbourne, Melbourne, Australia; Murdoch Children’s Research Institute, Melbourne; Emergency Department, Royal Children’s Hospital, Melbourne; School of Nursing, Faculty of Health Sciences, University of Ottawa; Department of Paediatrics, The University of Melbourne, Melbourne

More than 40 multidimensional observational scales have been developed to assess and quantify pain intensity in infants and children. Scale parameters are a combination of behaviors (facial expressions, body movements, and crying) and physiological parameters (heart rate, oxygen saturation, and blood pressure). The Face, Legs, Activity, Cry, and Consolability (FLACC) scale, designed to assess postsurgical pain in young children, scores pain intensity by rating five behaviors on a 0–2 scale: face, legs, activity, consolability, and cry, resulting in a maximum score of 10.

The objectives of this systematic review were to determine the suitability of the FLACC scale to assess pain in infants and children by rigorously evaluating the psychometric properties of the scale; specifically, to identify and describe studies providing psychometric data and the populations and circumstances to which FLACC has been applied in these studies; systematically review the quality of these studies using appropriate assessment tools; analyze and synthesize the evidence for the psychometric and practical properties (feasibility and utility) of the FLACC scale; and provide contemporary recommendations for the scale’s role in pain assessment.

A number of concerns about the validity of the FLACC scale emerged. For example, the results of two studies, one using the Facial Action Coding System and the other the Child Facial Coding System, demonstrated that infants and children rarely showed “jaw clenching” or “chin quivering” as an indication of pain, both of which are descriptors for the FLACC facial expression item. Results confirmed concerns about reliability, face, and convergent validity, and the investigators concluded that when behavioral descriptors are inconsistent with what is observed empirically, the scales are likely to perform less effectively. Furthermore, several of the descriptors of the FLACC are open to interpretation.

The weight of evidence for the reliability and validity of the FLACC scale, as applied to infants and children ages 2 months to 7 years who experience postsurgical pain, is sufficient to recommend the scale’s use in this setting. However, the results of this review challenge the popular view that the strong psychometric properties of the FLACC scale support its use to assess pain in children from infancy to adolescence in a range of circumstances. The data used to support the psychometric properties of the scale, in particular, validity, are either absent or limited and frequently derived from studies with methodological flaws. Further work is required to provide a foundation upon which confident recommendations about the future of the FLACC scale in pediatric pain assessment can be made.

Clinical Journal of Pain


The following highlights summarize selected articles from Clinical Journal of Pain (Volume 31, No. 11, November 2015 Issue).

SCN9A Variants May be Implicated in Neuropathic Pain Associated with Diabetic Peripheral Neuropathy and Pain Severity

Qingqin S. Li, Peter Cheng, Reyna Favis, Alan Wickenden, Gary Romano, and Hao Wang; Neuroscience Therapeutic Area, Janssen Research & Development, LLC, Titusville, NJ; Neuroscience Therapeutic Area, Janssen Research & Development, LLC, Raritan, NJ; Aranea, Janssen Research & Development, LLC, La Jolla, CA; Neuroscience Therapeutic Area, Janssen Research & Development, LLC, Spring House, PA

Although there are many causes of neuropathic pain, diabetes mellitus is the most common cause, with 50%–60% of patients developing neuropathy as a long-term complication and 10%–26% experiencing neuropathic pain. Neuropathic pain can be severe and difficult to treat. Several medications have shown efficacy in treating diabetic peripheral neuropathy (DPN) pain, including tricyclic antidepressants, the serotonin noradrenaline reuptake inhibitor duloxetine, anticonvulsants such as pregabalin and gabapentin, and opioid analgesics such as oxycodone. However, treatment for many patients with painful diabetic neuropathy is limited by modest efficacy or significant side effects associated with these agents. In this study, investigators interrogated the relationship between common and rare variants in the SCN9A gene and chronic neuropathic pain associated with DPN in a case-control study using a 2-stage design.

Through use of common and rare variant approaches, this study’s findings suggest a possible role for uncommon and rare variants of SCN9A in the disease etiology of DPN-related neuropathic pain. Seven variants were associated with neuropathic pain at the sequencing stage. Four variants were confirmed by genotyping to occur at a higher frequency among cases than controls. Uncommon and rare variants were associated with neuropathic pain and pain severity score.

These findings may facilitate the evaluation of Nav1.7 blockers in this patient population, although a specific genetically defined subpopulation cannot be easily identified because of allelic heterogeneity. The p.D1908G mutant channel has not yet been characterized in detail, and future characterization of this mutation and the intronic variant is warranted.

Ultralow Dose of Naloxone as an Adjuvant to Intrathecal Morphine Infusion Improves Perceived Quality of Sleep but Fails to Alter Persistent Pain: A Randomized, Double-Blind, Controlled Study

Linda Block, Christopher Lundborg, Jan Bjersing, Peter Dahm, Elisabeth Hansson, and Björn Biber; Department of Anesthesiology and Intensive Care Medicine, Department of Rheumatology, Institute of Clinical Sciences; Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Conventional pain therapies are insufficient for some patients with severe long-term pain. This study focused on the potential beneficial effects achieved by supplementing intrathecal (IT) continuous morphine infusion with concurrent and similarly administered naloxone (NAL). This randomized, cross-over, double-blind, controlled study was performed in a group with a history of long-term, difficult-to-treat pain and uninterrupted IT morphine therapy. The objective was to investigate whether the addition of simultaneous IT administration of NAL would confer improved analgesia and quality of sleep, alter patients’ quality of life, or change the levels of proinflammatory and antiinflammatory cytokines in the blood.

This study’s key finding was that the addition of NAL40 for patients with persistent noncancer pain, who were being treated with continuous IT morphine infusion, was associated with improvements in self-reported sleep. This finding illustrates a potential beneficial role for ultralow doses of NAL as an adjuvant to IT morphine. Importantly, the effects of NAL40 were significantly better than effects following the sham treatment procedure. All study patients who reported an increased level of activity also reported improved quality of sleep.

Future research in larger, well-defined patient cohorts that focuses on unknown mechanisms for pain versus sleep interactions is needed. Such studies would ideally use sleep laboratory methodology. One noteworthy observation was that patients who experienced improved pain relief with any dose of NAL had a daily mean morphine dose of 1.13 mg IT. However, patients who did not experience any improvement in pain relief had a daily mean morphine dose of 2.84 mg IT. An optimal morphine/NAL ratio needs to be identified to achieve desired results.