Society

APS Responds to FDA REMS Decision

The following statement was issued by the American Pain Society (APS) in response to the July 9 announcement by the FDA of its extended-release, long-acting opioid REMS decision.

GLENVIEW, Ill., July 11, 2012—The FDA's Risk Evaluation and Mitigation Strategies (REMS) for extended release/long-acting (ER/LA) opioids, announced on July 9, is consistent with APS's strong belief that competency-based educational programs will benefit both primary care and specialty prescribers of ER/LA opioids and ultimately improve patient safety and decrease diversion while still assuring access to these medications for patients who need them.

Professional and consumer education programs can achieve significant benefits for improving awareness and reducing behaviors that contribute to opioid abuse. For example, the FDA's mandate that simplified medication guides and information sheets for ER/LA opioids be made available for patients will hopefully lead to improved knowledge concerning proper use, storage, and disposal of these drugs and result in less intentional and unintentional diversion of these medicines.

The educational opportunities for prescribers and dispensers mandated by the REMS should be offered through a variety of channels. APS and other professional societies can play a vital role in helping to develop educational modules as part of the REMS programs implemented by FDA and drug manufacturers. Clinician training programs should be evidence-based, and designed to develop and improve clinical skills such as patient assessment, communication, and recognition of risks for abuse as the basis for developing integrated treatment plans, revising treatment plans, and making referrals to pain specialists as necessary.

Despite our appreciation for the ER/LA REMS as announced, APS continues to disagree with FDA's decision to limit REMS to extended-release, long-acting opioids only. All opioids must be used, stored, and disposed of in similar ways for maximum safety.

This press release is also available on the APS website.

APS Welcomes New President Roger B. Fillingim, PhD, University of Florida Psychologist

Roger B. Fillingim, PhD, professor in the College of Dentistry and director of the Pain Research and Intervention Center of Excellence at the University of Florida, has begun a 2-year term as APS President. Dr. Fillingim has been an active leader in APS for many years, including serving as chair of both the Scientific Program and Education Advisory committees. In 2009, he received the APS Wilbert E. Fordyce Clinical Investigator Award for his clinical pain scholarship and research achievements.

Dr. Fillingim would like to see APS become more active in its advocacy role. "There are several important issues we must address on behalf of the pain community, such as balancing the benefits and risks associated with pain medications, securing more funding for pain research, and enhancing access to evidence-based interdisciplinary pain care for patients in need," he says. Dr. Fillingim hopes to achieve these goals by collaborating with other organizations, including patient advocacy groups, professional societies, private industry, and government agencies.

Read more about Fillingim's achievements and hopes for the Society in the recent APS press release.

Call for Award Nominations

The APS Awards Committee invites nominations for awards to be presented at the 32nd Annual Scientific Meeting, May 8–11, 2013, in New Orleans, LA. For a full listing of awards and to make one or more award nominations, visit the APS website and complete the electronic nomination form. Please be sure to include all of the requested information. All nominations should be completed online by August 1. Please e-mail Amy Kephart, APS staff, at akephart@ampainsoc.org with any questions.

Join APS in the Crescent City: Save the Date 2013

The 2013 APS Annual Scientific Meeting will be held in New Orleans, LA, May 8–11, and will offer current information about the diagnosis, treatment, and management of acute pain, chronic cancer and noncancer pain, and recurrent pain. For more information, visit www.APSScientificMeeting.org.

APS Members Can Now Access Journal of Pain Using Single Sign-On

As an APS member, you can now fully access The Journal of Pain online when you use your APS member login on the APS website. This feature saves you the extra step of having to log in to multiple sites and provides access directly from the APS website. Simply log in to the APS members only area with your APS member password and click "Journal of Pain" under "Publications." If you have any questions, contact APS Member Services at 847.375.4715.

APS to Present Sessions at the 2012 PAINWeek Conference

APS is partnering with PAINWeek in September to present sessions on the theme "American Pain Society: Translating Science into Practice." The sessions will take place on Friday, September 7, as part of the PAINWeek program in Las Vegas, NV, September 5–8. The four 1-hour sessions will address practical application of the science behind treatment approaches for migraine, cognitive and behavioral treatments, analgesic development, and the use of opioid analgesics. Faculty will include Charles Argoff, MD; David Dodick, MD; Roger Fillingim, PhD; Jennifer Haythornthwaite, PhD; and Mark Wallace, MD.

About PAINWeek

PAINWeek is the nation's largest pain conference for frontline practitioners with an interest in pain management and will again welcome more than 1,500 physicians, nurses, pharmacists, and other healthcare professionals for a comprehensive program of course offerings, satellite events, and exhibits. More than 100 hours of continuing medical education activities will be presented. To learn more and register for PAINWeek 2012, visit www.painweek.org.

APS President Roger Fillingim, PhD, says of the event, "APS is pleased to collaborate with PAINWeek and introduce the Society to its frontline practitioners. Our goal is to provide a timely and relevant program that will speak to the mission and direction of APS within the pain management landscape." Director of Program Development for PAINWeek Debra Weiner adds, "We are excited to welcome APS to PAINWeek. Inclusiveness has been our byword from the beginning, and it is very gratifying to have such an esteemed organization contribute to the national conference."

Research

2012 Future Leaders in Pain Research Grants Program: Deadline Extended to July 23

The call for applications for the 2012 Future Leaders in Pain Research Grants Program is now extended to July 23, 11:59 pm PDT. This year APS will again award at least two grants in the amount of $20,000 each to those research proposals demonstrating the greatest merit and potential for success. This grant program was established to fund research projects of doctorally prepared investigators who have not yet attained NIH RO1–level funding. The program's intent is to encourage research in pain that will add to the body of knowledge and to allow investigators to develop pilot data that will aid them in securing additional major grant funding.

For more information regarding deadlines, eligibility, topics, and more, please visit the Future Leaders in Pain Research Grants page on the APS website.

Renowned Researcher to Lead New Multidisciplinary Pain Program at NIH

Catherine Bushnell, PhD, an internationally recognized pain and neuroscience researcher, has been appointed scientific director of a new research program focusing on the role of the brain in perceiving, modifying, and managing pain. Based in the National Center for Complementary and Alternative Medicine (NCCAM), part of the National Institutes of Health (NIH), this collaborative effort will complement basic science and clinical research efforts of other ongoing intramural neuroscience, imaging, and mental and behavioral health research programs.

According to the Institute of Medicine (IOM), more than 100 million people suffer from chronic pain conditions in the United States, and it is estimated to cost nearly $635 billion annually for treatment and lost productivity. While tremendous progress has been made in drug treatment of acute pain, there are pressing needs for better understanding and treatments for chronic pain.

"Dr. Bushnell's work has profoundly changed the ways in which we understand and study this very important problem," said NCCAM Director Josephine P. Briggs, MD. "Under her leadership, this program will continue to work toward the development of better ways to safely and more effectively treat chronic pain, and advance research on the intersection and integration of pharmacological and non-pharmacological approaches."

Research projects will include investigating the role of the brain in pain processing and control, and how factors such as emotion, attention, environment, and genetics affect pain perception. The program will also explore how chronic pain produces changes in the brain that can modify how the brain reacts to pain medications like opioids.

"Dr. Bushnell is a pioneer in the field of pain research, and NIH is extremely fortunate to have her leading this research program," said Michael Gottesman, deputy director for intramural research. "She and her team will add a novel and important component to NIH's overall intramural neuroscience research community."

Dr. Bushnell comes to NIH from McGill University in Montreal, where she was the Harold Griffith Professor of Anesthesia and professor in dentistry and neurology. Dr. Bushnell's research interests include brain mechanisms of pain processing, psychological modulation of pain, and brain changes in chronic pain patients. Recent research projects utilize brain imaging and psychophysical testing to study the neural basis of pain processing.

"I am honored to have been selected to collaborate and work with one of the strongest neuroscience research programs in the world," Dr. Bushnell said. "It is an exciting and promising time in the field of pain research and I look forward to strengthening our understanding of the mechanisms and modulation of pain."

Dr. Bushnell just finished a term as president of the Canadian Pain Society and is treasurer of the International Association for the Study of Pain. She was director of the Alan Edwards Centre for Research on Pain at McGill from 2003 to 2009. In 2009, she was awarded a senior Canada Research Chair in Clinical Pain. Dr. Bushnell's scientific work has been recognized internationally, as demonstrated by her receipt of lifetime achievement awards from both the American Pain Society and the Canadian Pain Society. She began her scientific career at NIH in 1976, when she joined the National Institute of Dental and Craniofacial Research, then known as the National Institute of Dental Research, as a psychologist exploring the psychological aspects of pain processing. Dr. Bushnell received a Ph.D. in experimental psychology from the American University in Washington, D.C. in 1977 and postdoctoral training in neurophysiology at NIH. She has authored more than 100 publications in the field.

The program will be the focus of NCCAM's Division of Intramural Research, located on the NIH campus in Bethesda, MD.

Advocacy

Be Heard—Write an Op-Ed Article

Newspapers publish op-ed articles from guest contributors on their editorial pages to showcase different points of view on major issues in the news. Pain care and pain medications certainly have garnered their share of coverage recently, and you may have thought it would be worthwhile to express your views in an op-ed article for your local newspaper.

APS has developed two template op-ed articles now available to members for use in crafting their own op-ed submissions. They provide a basic framework and storyline, and members can adapt as much of the information as they wish for writing op-ed articles. The template pieces are "Time to Balance Public Discourse on Pain Drugs" and "Limiting Access to Care Not the Answer for Drug Misuse."

APS members interested in writing op-ed articles can contact Erin Abbey, APS Marketing Director, for assistance by e-mailing eabbey@ampainsoc.org.

Members

What is your area of specialty?
My research program has two primary areas of focus. First, I have had a long-standing interest in pain assessment, given that valid and reliable measurement is a basic requirement for both good clinical care and our scientific understanding of pain. For this reason, one ongoing area of interest is the evaluation—and development, as needed—of measures of pain. Second, as a clinical psychologist, I study the efficacy and mechanisms of psychosocial pain treatments. Most recently, I have been examining the efficacy and mechanisms of electroencephalogram (EEG) biofeedback (also known as "neurofeedback") and self-hypnosis training as strategies for teaching patients with pain to alter brain activity directly as a means of creating more comfort.

What initially sparked your interest in working in your field? Briefly describe your career path.
I trace my interest in pain to Monty Python and Dr. Who. I went to graduate school with an intent to study depression. However, the faculty member who specialized in this area was not able to take on new students when I started graduate school. Therefore, I interviewed the other faculty members in the department and ended up finding one—Paul Karoly—who shared my sense of humor and enjoyment of science fiction. I enjoyed speaking with him so much that I decided to work with him, and only after making this decision did I learn that his interest was in health psychology. As I began to understand the importance of psychological factors as contributing to the experience of and adjustment to pain, as well as the plethora of interesting questions in this area that have yet to be answered, I was hooked.

What has been a highlight of your work? Perhaps you and your staff are proud of a certain project or accomplishment.
I hope that I have contributed to our understanding of the strengths and weaknesses of the many measures of pain that are available and, therefore, made it easier for clinicians and researchers to make informed decisions regarding the measures to use. I am also happy to have contributed to the development of a number of measures that help us understand the specific pain-related beliefs and coping responses that are most important to adjustment to chronic pain. In addition, I think our research on various psychosocial treatments, including cognitive-behavioral therapy and self-hypnosis training, has helped us to better understand their efficacy.

Is there a particular challenge that you've either overcome or hope to address soon?
All our treatments, including both biomedical and psychosocial treatments, are only effective for subsets of individuals. One challenge for our field is to better understand how these treatments can be used together (or matched to appropriate patients) to maximize positive outcomes for the most number of people. Also, we now have tens, if not thousands, of psychosocial treatments available, and more seem to be developed each year, yet I suspect that all of these treatments are effective because they influence a finite set of very specific mechanisms, such as behavioral coping responses, cognitive content (what people think about pain), and cognitive processes (how people related to their pain beliefs). I am interested in participating in more research that helps to identify the relative importance of these very specific mechanisms.

Who is your favorite role model—and why?
I have many role models in the field whose work has inspired me. These include my first academic mentor, Paul Karoly, who was incredibly encouraging and supportive of my ideas (some of which were less useful than others) and provided me with many opportunities to communicate some of these ideas in the research literature. Wilbert Fordyce is another hero, whose clear thinking, clinical work, and warm support during my predoctoral and postdoctoral internship inspired me to continue to work in this area.

How has membership in APS been of value to you and your professional development?
It is clear that pain cannot be adequately understood (or effectively treated) by a single discipline or approach. Focusing only on the psychology of pain, the social aspects of pain, or the biology of pain will fail in most cases. APS provides critical mechanisms, for example, through the Journal of Pain and our annual scientific meetings, for communicating across disciplines and moving the field forward.

Summaries

The Journal of Pain Highlights

The following highlights summarize selected articles from July 2012 (volume 13, number 7).

Study Assesses Pain and Quality of Life in Ugandan HIV Patients
Eve Namisango, Richard Harding, Leonard Atuhaire, Henry Ddungu, Elly Katabira, Fred Roland Muwanika, and Richard A. Powell; African Palliative Care Association, King's College London, University of Cape Town, and Makerere University.

Sub-Saharan Africa accounts for 69% of HIV cases worldwide and 72% of AIDS deaths. A study published in The Journal of Pain showed that pain is highly prevalent among well-functioning HIV patients in Africa, has a debilitating impact on quality of life, and that there is a significant level of unmet need for pain relief.

Although it is well known that pain occurs throughout the disease experience, few studies have looked at the frequency and severity of pain in HIV patients in Africa. Most research on HIV-related pain has been conducted in economically developed nations and predominantly on male patients. Researchers from the African Palliative Care Association in Kampal, Uganda, and Kings College London examined the 3-day period prevalence of pain among ambulatory HIV patients in two Ugandan outpatient sites. They sought to assess the association of pain with antiretroviral therapy (ART), and the relationship between pain, function, and quality of life.

Study participants were recruited at HIV clinics, were at least 18 years old with a confirmed HIV diagnosis, and possessed sufficient cognitive and physical ability to participate in the study. Questionnaires were completed by the patients to elicit responses regarding pain and pain intensity, gender differences in pain, physical symptoms burden, functionality, and overall quality of life. Three hundred two patients participated in the study.

Results showed that 47% of the patients reported pain 7 days prior to completing the surveys. Of those with pain, 53% said it was mild, 20% described their pain as moderate, and 27% called it severe. Gender was not associated with pain intensity. However, pain intensity was significantly associated with reduced function, increasing number of symptoms, and advanced HIV disease. The authors also found that pain was not associated with ART, and there was a significant level of unmet need for pain relief.

Estrogen Receptor Activation May Provide Therapeutic Target for Irritable Bowel Syndrome
Dong-Yuan Cao, Yaping Ji, Bin Tang, and Richard J. Traub; University of Maryland

Some painful conditions, such as irritable bowel syndrome, are more common in women and hormonal modulation of nociceptive activity is believed to be the cause for the higher gender-based prevalence. A study published in The Journal of Pain showed that, in rats, the activation of Estrogen Receptor (ER) ß is antinociceptive in the colorectal distention model of visceral pain and may provide a therapeutic target to manage irritable bowel syndrome.

The purpose of the study was to investigate the role of ER ß in visceral nociceptive processing. The effects of selective ER ß agonists were evaluated in ovariectomized and normal female rats. Results showed that injection of the ER ß agonist attenuated the viseromotor response after 4 hours. The visceral antinociception by ER ß was confirmed by electrophysiology analysis and suggested that the effect occurred at the spinal cord. The authors noted that the 4-hour response delay indicated that a rapid membrane-initiated signaling mechanism is not involved.

The results indicate that ER ß's antinociceptive effects on visceral pain could provide a therapeutic target for managing irritable bowel syndrome and the antidepressive actions of ER ß agonists also might be beneficial because stress can trigger or exacerbate the condition.

Pain Medicine Highlights

The following highlights summarize selected articles from the June 2012 issue (volume 13, issue 6).

Is Spinal Manipulation Effective for Pain? An Overview of Systematic Reviews
Paul Posadzki

This article critically evaluated data from systematic reviews (SRs) of spinal manipulation (SM) as a pain management option. Four electronic databases were searched to identify all relevant articles on the effectiveness of SM for pain. Twenty-two SRs related to low-back pain (LBP), headache, neck pain, any medical problem, carpal tunnel syndrome, dysmenorrhea, fibromyalgia, lateral epicondylitis, musculoskeletal conditions, and nonspinal pain were identified.

Unanimously positive conclusions were drawn for none of these conditions. Collectively, these data fail to demonstrate that SM is an effective intervention for pain management. SM is a technique commonly used by chiropractors, osteopaths, physiotherapists, physicians, bone setters, and other manual therapists. Despite unproven safety and debatable effectiveness and cost-effectiveness, SM is still widely used to treat a wide range of pain-related conditions (among others). Hundreds of randomized clinical trials of SM have been published in the literature; however, their data are less than uniform.

The conclusions of SRs of SM for back pain appear to be influenced by authorship. Osteopaths or chiropractors seem to publish low-methodological-quality SRs associated with positive conclusions. Four (80%) of the five SRs published either by chiropractors or osteopaths arrived at overtly positive conclusions, and 16 (94%) of the 17 SRs by independent research groups reached negative or equivocal conclusions. The highest degree of ambiguity in the included SRs has been noticed for LBP. In addition, several hundred severe complications after upper SM have been reported although the estimates as to the incidence of these complications vary hugely. A particular concern relates to vascular accidents caused by arterial dissection after upper SM.

Randomized, Double-Blind, Placebo-Controlled Study of the Abuse Potential of Different Formulations of Oral Oxycodone
Lynn R. Webster, Brad Bath, Robert A. Medve, Tonya Marmon, and Gregory J. Stoddard; Lifetree Clinical Research, Nektar Therapeutics, Synteract, Inc., and University of Utah School of Medicine

The purpose of the present study was to evaluate the pharmacokinetics and associated abuse potential of several formulations of oral oxycodone among recreational opioid abusers. Participants completed an 8-day, placebo-controlled trial with four phases: a naloxone challenge, double-blind drug discrimination, double-blind abuse liability, and discontinuation. Nineteen healthy, male, recreational drug abusers participated in this study. Participants were administered different doses and formulations of oxycodone (40 mg immediate release [IR], 40 mg controlled release [CR], crushed 40 mg CR, and 80 mg CR) to evaluate pharmacokinetic parameters and ratings of drug liking and high. Pharmacokinetic parameters were determined over a 12-hour dosing interval.

Intact, orally administered oxycodone CR produced less drug liking and high than IR oxycodone and required approximately twofold higher doses to produce subjective effects comparable to IR oxycodone The length of time spent abusing a particular opioid has also been associated with a transition to nonoral routes of administration. In contrast, more than 97% of nonmedical users of prescription opioids prefer taking opioids orally, with fewer than 20% reporting the use of alternative routes of administration. Because the vast majority of misuse and abuse of prescription opioids occurs through the oral route, it is important to understand the characteristics of prescription opioids that might determine their abuse potential.

The results of this study suggest that the intact CR formulation of oxycodone may have less abuse potential than the IR and CR formulations that have been altered by crushing, which defeats their controlled-release properties.

PAIN Highlights

The following highlights summarize selected articles from July 2012 (volume 153, issue 7).

Cognitive Behavioral Therapy Increases Pain-Evoked Activation of the Prefrontal Cortex in Patients with Fibromyalgeia
Karin B. Jensen, Eva Kosek, Rikard Wicksell, Mike Kemani, Gunnar Olsson, Julia V. Merle, Diana Kadetoff, and Martin Ingvar; Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Karolinska Institutet, and Charité Universitätsmedizin Berlin

Interventions based on cognitive behavioral therapy (CBT) are widely used to treat chronic pain, but the brain mechanisms responsible for these treatment effects are poorly understood. The aim of this study was to validate the relevance of cortical control theory in response to an exposure-based form of CBT, acceptance, and commitment therapy, in patients with chronic pain.

Forty-three women with fibromyalgia were enrolled in a randomized, 12-week, waiting-list-controlled clinical trial. CBT was administered in groups of six patients during 12 weekly sessions. Functional magnetic resonance imaging performed during pressure-evoked pain was assessed before and after treatment or the 12-week period. Self-report questionnaires of depression and anxiety were administered pre- and posttreatment as well as 3 months after treatment ended.

Patients treated with CBT reported larger improvement of fibromyalgia on the Patient Global Impression of Change measure and improved depression and anxiety symptoms compared to waiting-list controls. However, there were no effects on clinical pain or pain sensitivity measures.

These authors suggest that CBT changes the brain's pain processing through an altered cerebral loop between pain signals, emotions, and cognition, leading to increased access to executive regions for reappraisal of pain. These data support the authors' hypothesis about the activation of a cortical control mechanism in response to CBT treatment in chronic pain.

Noninvasive Cortical Modulation of Experimental Pain
Veit Mylius, Jeffrey J. Borckardt, and Jean-Pascal Lefaucheur; Université Paris Est Créteil, Philipps-Universität Marburg, Medical University of South Carolina, and Hôpitaux de Paris

Noninvasive cortical stimulation (NICS) can produce analgesic effects by means of repetitive transcranial magnetic stimulation or transcranial direct current stimulation. Such effects have been demonstrated on chronic ongoing pain, as in acute provoked pain. The investigation of induced changes in the perception of experimental pain by NICS can help clinicians and researchers better understand the mechanisms of action involved with these techniques and the role played by the cortex in the integration of nociceptive information. This review presents current data on the modulation of experimental pain perception by cortical stimulation.

The different results observed in acute provoked pain and chronic pain of either neuropathic or nonneuropathic origin suggest that cortical stimulation may modulate various aspects of pain according to the activation of various neural circuits. It is a therapeutic challenge to determine which circuit should be recruited by cortical stimulation to obtain pain relief with respect to the origin of pain, its clinical presentation, or its underlying pathological condition. Further studies of the modulation of experimental pain by cortical stimulation can help to achieve this goal.

In particular, the evaluation of new targets, parameters, and pain conditions to better understand the mechanisms of action of pain processing cortical modulation may greatly benefit patients in pain.

In the Media

Meeting Highlights from American Pain Society 31st Annual Scientific Meeting (Practical Pain Management)

Sufficient Cancer Pain Relief May Mean Frequent Follow Up (News-Medical.net)

Pain is More Prevalent in Poor Populations (Desert News)

Marijuana Spray Proves Effective as Cancer Pain Treatment (American News Report)

Antidepressant May Work Against Chemo-Related Peripheral Neuropathy (WebMD)

Preoperative Breast Cancer Pain Involves an Inflammatory Process (News-Medical.net)

U.S. War on Drugs Moves to Pharmacy from Jungle (Reuters)

After Delay, OxyContin's Use in Young Is Under Study (New York Times)

FDA Won't Order Doctors to Get Pain-Drug Training (New York Times)

Call for Submissions

Do you have a topic that is relevant to APS members? Is there a member who is doing work that APS should spotlight? Is there a funding opportunity APS members need to know about? Please submit stories, events, and more to enews@ampainsoc.org for consideration.