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VA research on

Pain Management


Pain is one of the most common reasons Americans consult a physician, and joint and back pain and other musculoskeletal ailments are the most common diagnoses among Iraq and Afghanistan Veterans.

According to a 2015 report by the National Institutes of Health (NIH), 25.3 million American adults (11.3 percent of the total population) had pain every day for the preceding three months. Nearly 40 million adults (17.6 percent) experience severe levels of pain.

The consequences of chronic pain include lost work productivity, disability, and increased health care costs. Unrelieved and persistent chronic pain contributes to depression, anxiety, poor sleep patterns, decreased quality of life and often times, substance use disorder. It is also a risk factor for suicide.

VA's National Pain Management Strategy provides a system-wide standard of care to reduce suffering from preventable pain. As part of that strategy, the department's pain research portfolio covers a wide range of topics, from drug discovery to complementary and integrative treatments, to the impact of pain on daily function and quality of life. The strategy helps set the direction of VA pain research, which in turn helps inform and refine the strategy.

For patients interested in treatments other than medication, or in addition to medication, complementary and integrative medicine is a popular option. A wide range of these therapies and treatments, such as acupuncture and yoga, are proving valuable in helping Veterans manage their pain.


Selected Major Accomplishments

  • 2008: Established the VA Pain Research, Informatics, Multimorbidities, and Education (PRIME) Center to study the interaction between pain and associated chronic conditions and behavioral health factors
  • 2014: Announced, along with NIH, a five-year, $21.7 million quality-improvement initiative to research non-drug approaches to managing pain and related health conditions
  • 2015
    • Found that ion channels—specialized proteins in the membrane of brain cells—are heavily implicated in the biological mechanisms that generate and sustain neuropathic pain
    • Determined that VA's stepped-care model of pain management for chronic pain resulted in significant reductions in pain-related disability, pain interference and pain severity in Veterans with chronic musculoskeletal pain compared with usual care
  • 2016: Established a musculoskeletal diagnosis cohort to characterize variation in pain, comorbidities, treatment, and outcomes among more than 5 million patients with musculoskeletal disorders receiving care from VA


New, Ongoing, and Published Research

VA researchers are working to develop new approaches to alleviate Veterans' pain, which may result from spinal cord injury, burns, amputations, traumatic brain injury, cancer, or musculoskeletal conditions. Some types of chronic pain, such as the nerve pain experienced by many people with spinal cord injury, are very difficult to treat.

Other investigators are conducting studies to determine which complementary and integrative pain therapies are truly effective, and for which conditions and populations they work.

➤ Center for Neuroscience and Regeneration Research

Biomedical research conducted by VA investigators has contributed to the scientific understanding of pain, especially nerve pain. Among the pioneers in this area has been Dr. Stephen Waxman. Waxman is the director of the Center for Neuroscience and Regeneration Research, a collaboration among VA, the Yale University School of Medicine, the Paralyzed Veterans of America, and the United Spinal Association.

The center is a state-of-the-art research facility dedicated to molecular and cell-based discoveries that might lead to the restoration and preservation of nervous system function.

Waxman and his colleagues have discovered that ion channels (particularly channels that move sodium) change following injury or disease and play a role in the development of chronic pain.

Ions are atoms or molecules with a net electric charge due to the loss or gain of one or more electrons. An ion channel is a protein structure embedded in a cell's membrane that moves ions across the membrane without the use of additional energy.

Recent work at the center has identified and characterized new mutations in sodium channels that produce neuronal hyperexcitability (excessive activity) and severe pain in people with rare genetic diseases or common peripheral nerve diseases.

Other work has identified and characterized a new gene variation, or polymorphism, that increases a person's risk for neuropathic pain. (Neuropathic pain is a complex, chronic pain state that is usually accompanied by tissue injury.) Treating people with a sodium channel blocker (lamotrigine) provided some relief to two pairs of twin sisters in a family who had the same kind of unusual pain after exercising. This led the researchers to conclude that a sodium channel mutation was directly related to the twins' pain.


➤ Pain, Research, Informatics, Medical comorbidities, and Education (PRIME) Center

VA's Pain, Research, Informatics, Medical Comorbidities, and Education (PRIME) Center, part of the VA Connecticut Healthcare System, conducts research to improve pain care and sponsors educational activities for Veterans and clinical staff. The PRIME Center's goals include advancing scientific knowledge and significantly impacting the care of Veterans living with pain and associated chronic conditions, such as depression or PTSD.

To meet these goals, the Center studies the interactions between pain and associated chronic conditions and behavioral health factors to develop and implement effective interventions that can reduce pain, the negative impacts of pain on emotional and physical functioning, and the overall disease burden pain causes by employing principles of medical informatics, behavioral science, and health services research.


➤ Tampa VAMC Chronic Pain Rehabilitation Program (CPRP)

VA's Chronic Pain Rehabilitation Program, located at the James A. Haley Veterans Hospital in Tampa, Fla., is a nationally known center for chronic pain research, treatment, and education. The CPRP is the only Commission on Accreditation of Rehabilitation Facilities (CARF) inpatient pain treatment center in the VA system.

The CPRP is a referral-based program for Veterans with chronic pain, including those living out-of-state. It offers inpatient and outpatient rehabilitation programs to help Veterans manage their chronic pain condition.


➤ CREATE: Pain Management and Patient Aligned Care

VA's Collaborative Research to Enhance and Advance Transformation and Excellence (CREATE) funding initiative encourages VA investigators to collaborate with other VA partners to conduct research on high-priority issues that affect the health and health care of Veterans.

VA's Pain Management and Patient Aligned Care CREATE has three specific goals: to enhance Veterans' access to pain care; to use health information technology to promote better pain care for Veterans; and to build sustainable improvements in pain care. The program is anchored by three projects:

  • Longitudinal Musculoskeletal Cohort Study—This study will examine variations in pain, pain treatment, the effects of co-existing conditions, and outcomes among Veterans receiving care from VA. The study's results will be used to transform pain care and management within VA.
  • Effective Screening for Pain Study—This ongoing study aims to evaluate the effects of an enhanced, computer-aided pain screening and assessment tool to allow for the use of pain and function scores as an alternative to the currently used numerically-based pain rating scale. The study's results will help improve the quality and clinical usefulness of the routine screenings for pain VA provides Veterans at every health encounter.
  • Comprehensive Opioid Management in Patient Aligned Care Teams (COMPACT)—The COMPACT study is testing a telehealth-based self-management training system to promote improved care for Veterans receiving chronic opioid therapy. The primary aims of the study are to test the effectiveness of the system in improving physical and emotional functioning, the safe use of opioids, and quality of life. Because the COMPACT makes use of widely accessible automated telephone technology, researchers hypothesize that the training system will broaden access to pain care and can be delivered with consistency, thereby reducing variability in care.


➤ Interagency Pain Research Coordinating Committee (IPRCC) and Interagency Pain Research Collaboration

The Interagency Pain Research Coordinating Committee (IPRCC) is a federal advisory committee created by the Department of Health and Human Services to enhance pain research efforts and promote collaboration across the government.

National Pain Strategy—In 2015, the IPRCC created the National Pain Strategy (NPS). The strategy was created with input from VA clinicians and scientists as well as from academicians, advocates and other federal agencies.

The NPS provides guidelines for the effective treatment of pain across a person's lifetime. It emphasizes pain education and management and disparities in treatment. Although it is currently in draft form, the IPRCC is already using the strategy to harmonize pain research across federal agencies.

Complementary and integrative pain management—VA researchers are also collaborating with NIH's National Center for Complementary and Integrative Health (NCCIH, formerly NCCAM) to support studies on effective complementary and integrative approaches to pain management in Veterans with both physical and mental health conditions.

In 2014, VA and NCCIH jointly announced a $21.7 million research program focused on the use of complementary approaches to treat chronic pain in the Veteran population, and to determine whether treatments such as yoga, acupuncture, and meditation can help Veterans manage their chronic painful conditions.

The 13 research projects in this program will help researchers better understand how complementary approaches to pain management can be better integrated with regular care. It will also help researchers determine for what conditions and for whom these complementary and alternative approaches pose benefit.


➤ Stepped care model for pain management

VA's Stepped Care Model for Pain Management (SCM-PM) gives clinicians the ability to assess and treat pain within a primary care setting, while enabling them to use other treatment options including specialized care and multidisciplinary approaches.

The model is designed to help Veterans by ensuring VA clinicians are fully trained in pain management techniques; that pain assessment is performed in a consistent manner throughout VA; and that Veterans receive prompt and appropriate pain treatment.

The SCM-PM also stresses the importance of equitable access to health care and the effective use of resources to prevent pain for enrolled Veterans.

In 2009, researchers at the Indianapolis VA Medical Center began the Stepped Care to Optimize Pain Care Effectiveness (SCOPE) study. The study, which took place at five primary care clinics and was completed in 2015, included 250 Veterans with persistent musculoskeletal pain (pain from both muscles and bones) who were receiving either usual forms of pain care or stepped care. Those receiving stepped care had their symptoms monitored by an automated system, and also received consults by telephone with a telephone-based pain specialist team to treat their pain.

The SCOPE study was followed by the Evaluation of Stepped Care for Chronic Pain (ESCAPE) clinical trial in 241 Veterans of the Afghanistan and Iraq conflicts. Results published in 2015 demonstrated that a stepped-care intervention that combined medication, self-management strategies, and brief cognitive behavioral therapy resulted in significant reductions in pain-related disability, pain interference, and pain severity in Veterans with chronic musculoskeletal pain.


➤ Center for Health Equity Research and Promotion

The Center for Health Equity Research and Promotion (CHERP) is a VA Health Services Research and Development Center of Innovation whose mission is to advance the quality and equity of health and health care for vulnerable Veteran populations. CHERP's research focuses on vulnerable Veteran populations, including those who face potential discrimination because of race, ethnicity, or social status, and those at risk for disparities in health or health care due to other physical or mental conditions.

CHERP is examining the associations of socio-economic status and geographic residence with pain management in Veterans. Researchers are:

  • identifying and quantifying disparities in health care and health outcomes between vulnerable and non-vulnerable populations;
  • identifying and understanding how multiple factors are associated with these disparities; and
  • designing and testing targeted interventions; assessing their efficacy, effectiveness, safety and cost, and translating successful interventions into widespread clinical practice and policy.


➤ Chronic back pain

Chronic back pain can change people's lives. The condition can be debilitating, making daily activities such as driving a car or sitting at a desk extremely difficult. As many as 40 percent of Veterans over 65 years old have chronic back pain.

Chronic low back pain as a syndrome—Dr. Debra K. Weiner, an investigator with the Pittsburgh VA Healthcare System and the University of Pittsburgh, is working to better understand chronic low back pain (CLBP) in older adults. She and her colleagues are developing a series of papers that present CLBP as a syndrome, a final common pathway for pain as a result of conditions in different parts of the body rather than a disease localized exclusively to the lumbosacral spine (the small of the back and the back part of the pelvis between the hips).

Each article will address one of 12 important contributors to pain and disability in older adults with CLBP. The first such article, published in 2015, focuses on hip osteoarthritis as a cause of CLBP.

Weiner is also a member of the National Institutes of Health's Task Force on Research Standards for CLBP. This task force is a group of federal and non-federal pain clinicians and researchers working together to draft standards for research on CLBP. It is hoped that these standards will allow pain researchers to use the same criteria when conducting clinical trials to make the results of the trials meaningful and comparable.

Chiropractic care—In 2014, researchers at the Canandaigua VA Medical Center looked at whether chiropractic care could relieve the disability caused by chronic back pain. They studied 136 Veterans aged 65 or older with lower back pain who had never received chiropractic care. Half relieved spinal manipulative therapy (SMT) from a chiropractor; the others received a sham treatment, similar to a placebo.

After 12 weeks, the researchers found that there was a statistically significant improvement in the level of disability of those who received SMT, but only the same level of reduction of pain as those who received the sham treatment. The team believes that the concern they showed about the pain of all patients in the study changed the way the Veterans felt about pain, and made them feel better.


➤ Over-prescription of opioids

Opioids are medications that relieve pain. They reduce the intensity of pain signals reaching the brain and affect those brain areas controlling emotion, which diminishes the effects of a painful stimulus. Medications that fall within this class include hydrocodones, such as Vicodin; oxycodones, such as OxyContin and Percocet; morphine, such as Kadian and Aviza; codeine; and related drugs.

Taken as prescribed, opioids can be used to manage pain safely and effectively. When abused, however, even a single large dose can cause severe respiratory depression and death. Regular or longer-term use and abuse of opioids can lead to physical dependence, and in some cases addiction.

Opioid prescription patterns—Most prescriptions for opioid painkillers are made by the broad swath of U.S. general practitioners, not by a limited group of specialists, according to a 2015 study by researchers at the Palo Alto VA Health Care System and the Stanford University School of Medicine.

The research team examined Medicare prescription drug claim data for 2013, and found that while the top 10 percent of opioid prescribers account for 57 percent of all opioid prescriptions, this prescribing pattern is comparable to that found in the Medicare data for prescribers of all drugs.

The team's findings contrast with previous studies by others that indicated the high levels of prescribing opioids in the United States is the result of a small population of prolific prescribers operating out of corrupt pill mills. According to the authors of the new study, efforts to curtail national opioid overprescribing must address a broad swath of prescribers to be effective.

Overdose from drug combinations—In another study published in 2015, VA researchers and researchers with the Alpert Medical School at Brown University and the University of Michigan Medical School found that nearly half of 2,400 Veterans who died from a drug overdose between 2004 and 2009 while they were receiving opioids for pain were also receiving benzodiazepines, or benzos, which are common medications for the treatment of anxiety, insomnia, and alcohol withdrawal.

The risk of overdose death for Veterans receiving both opioids and benzodiazepines was four times greater than in those receiving opioids alone. In addition, Veterans receiving higher doses of benzodiazepines while concurrently receiving opioids were at greater risk of overdose death than those on lower doses of benzodiazepines. According to the study's lead researcher, prescribing benzodiazepines to patients taking opioids for pain is "quite common," and therefore the team's findings are "deeply troubling."

Opioid Safety Initiative—In 2011, the Minneapolis VA Medical Center began developing an Opioid Safety Initiative (OSI). OSI was designed to decrease high-risk opioid prescribing practices, and to improve the safety of opioid prescribing while providing high-quality pain care for Veterans.

A 2015 study found that OSI, which emphasizes patient education, close patient monitoring with frequent feedback, and the use of complementary and integrative medicine practices like acupuncture and behavior therapy, can produce dramatic results.

Minneapolis researchers found that, from 2011 through 2014, the number of Veterans prescribed more than 200 morphine-equivalent milligrams worth of opioids decreased from 342 to 65. Overall, the number of unique pharmacy patients who received at least one opioid prescription decreased by almost 1,000 and the number of Veterans receiving oxycodone dropped from 292 to three.

Opioid use and new-onset depression—While opioids may cause short-term improvements in mood, their long-term use brings the risk of new-onset depression, according to a study published in 2016 by a team of researchers from VA and other academic institutions. The study looked at 70,997 VA patients, 13,777 patients from Baylor Scott & White Health (BSWH), and the Henry Ford Health System (HFHS). The patients were new opioid users, ages 18 to 80, who did not have a diagnosis of depression when they began taking their medication.

Twelve percent of the VA patients, 9 percent of the patients from BSWH, and 11 percent of the HFHS sample experienced new-onset depression after using opioid analgesics. The research team speculated that the findings may be explained by the possibility that using opioids for more than 30 days can lead to changes in neuroanatomy, and low testosterone.

Endomorphin vs. morphine—Another 2016 study, by researchers at the Southeast Louisiana Veterans Health Care System and Tulane University, compared several lab-made versions of the neurochemical endomorphin, which is found naturally in the body, to morphine, to measure their effectiveness and side effects. Neurochemicals are organic molecules, such as serotonin, dopamine, or nerve growth factor, which participate in neural activity.

The team found that the new endomorphin drug was not addictive in rats and did not cause motor impairment or potentially fatal respiratory problems. Also, the rats on which it was tested did not build up tolerance to it over time—all of which are problems with current opium-based painkillers.

The team hopes to begin clinical trials of the new drug on humans within the next two years.


➤ Opioid doses and risk of suicide

In a 2016 study, researchers with the VA Ann Arbor Healthcare System and University of Michigan found that Veterans receiving the highest doses of opioid painkillers were more than twice as likely to die by suicide, compared with those receiving the lowest doses.

The research team looked at nearly 124,000 Veterans who received VA care in 2004 and 2005. All had non-cancer chronic pain and received prescriptions for opioids. Using the National Death Index, the researchers identified 2,601 patients who died by suicide before the end of 2009.

They found that the suicide risk rose as dose increased. The researchers could not tell, however, whether there was a direct causal link between the pain medications and suicide risk. Instead, the high doses may be a marker for other factors that drive suicide, including unresolved severe chronic pain.


➤ Knee osteoarthritis

In 2015, researchers at the Durham (North Carolina) VA Medical Center and Duke University found, in a pilot study, that Swedish massage is an acceptable and feasible treatment for Veterans with osteoarthritis of the knee. The team looked at 25 Veterans, mostly men, with an average age of 57. The men also had an average body mass index of around 32, above the obesity threshold.

Of the original 25 Veterans in the study, 23 completed a regimen of eight weekly one-hour massage sessions. More than 90 percent of them said they wanted to continue to receive massage as part of their arthritis treatment plan, and nearly 90 percent thought other Veterans would try it if it were offered in VA.

They also reported, on average, about a 30 percent improvement in pain, stiffness, and function.


➤ Complementary and Integrative Medicine

VA researchers are examining the effectiveness of complementary approaches to treat pain, such as yoga, acupuncture, and a process called neuromodulation. Neuromodulation is a way to change the way nerve cells communicate with each other by applying a magnetic field or current to the head in key regions.

Scientists believe there is a "central" component to chronic pain; one that lies in the brain and how the brain responds to pain signals over time. Neuromodulation is a way of resetting the way nerve cells behave to pain and thus relieves pain that may not be treated traditionally. Transcranial magnetic stimulation (TMS) is already being used clinically for the treatment of depression and is now being tested to treat migraines as a result of traumatic brain injury and other painful conditions.

A 2015 study by researchers at the VA San Diego Healthcare System looked at 24 Veterans with headaches related to their mild traumatic brain injury. Half were given TMS treatment, and half were given a sham treatment instead. At one and four weeks after treatment, the group that received the TMS treatment had a significantly greater reduction in their headache pain.



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Selected Scientific Articles by Our Researchers

The influence of patient sex, provider sex, and sexist attitudes on pain treatment decisions. Hirsh AT, Hollingshead NA, Matthias MS, Bair MJ, Kroenke K. Patient and provider sex, but not some providers' sexist attitudes, influence pain care. J Pain. 2014 May;15(5):551-9.

Spinal manipulative therapy for chronic lower back pain in older Veterans: a prospective, randomized, placebo-controlled trial. Dougherty PE, Karuza J, Dunn AS, Savino D, Katz P. Spinal manipulative therapy did not result in greater improvement in pain when compared to a sham intervention, but it did demonstrate a slightly greater improvement in disability after 12 weeks. Geriatr Orthop Surg Rehabil. 2014 Dec;5(4):154-64.

Evaluation of stepped care for chronic pain (ESCAPE) in Veterans of the Iraq and Afghanistan conflicts: a randomized clinical trial. Bair MJ, Ang D, Wu J, Outcalt SD, Sargent C, Kempf C, Froman A, Schmid AA, Damush TM, Yu Z, Davis LW, Kroenke K. A stepped-care intervention that combined analgesics, self-management strategies, and brief cognitive behavioral therapy resulted in statistically significant reductions in pain-related disability, pain interference, and pain severity in Veterans with chronic musculoskeletal pain. JAMA Intern Med. 2015 May;175(5):682-9.

Opioid dose reduction in a VA health care system—implementation of a primary care population-level initiative. Westanmo A, Marshall P, Jones E, Burns K, Krebs EE. VA's Opioid Safety Initiative was associated with a substantial reduction in high-dose opioid prescribing. Pain Med, 2015 May;16(5):1019-26.

Deconstructing chronic low back pain in the older adult--step by step evidence and expert-based recommendations for evaluation and treatment: part I: Hip osteoarthritis. Weiner DK, Fang M, Gentili A, Kochersberger G, Marcum ZA, Rossi MI, Semla TP, Shega J. Presentation of an algorithm and supportive materials to help guide the care of older adults with hip osteoarthritis, an important contributor to chronic lower back pain. This is the first in a series of articles demonstrating that chronic low back pain involves more than the back. Pain Med. 2015 May;16(5):886-97.

The Domain II S4-S5 Linker in Nav1.9: A Missense Mutation Enhances Activation, Impairs Fast Inactivation, and Produces Human Painful Neuropathy. Han C, Yang Y, de Greef BT, Hoeijmakers JG, Gerrits MM, Verhamme C, Qu J, Lauria G, Merkies IS, Faber CG, Dib-Hajj SD, Waxman SG. Mutations in members of the sodium channel family in humans result in pain.

Neuromolecular Med. 2015 Jun;17(2):158-69. Pilot study of massage in Veterans with knee osteoarthritis. Juberg M, Jerger KK, Allen KD, Dmitrieva NO, Keever T, Perlman AI. Swedish massage is feasible and acceptable to VA health care users, and preliminary evidence suggests its efficacy for reducing pain due to knee osteoarthritis. J Altern Complement Med. 2015 Jun;21(6):333-8.

Benzodiazepine prescribing patterns and deaths from drug overdose among US Veterans receiving opioid analgesics: case-cohort study. Park TW, Saltz R, Ganoczy D, Ilgen MA, Bohnert AS. Among veterans receiving opioid analgesics, receipt of benzodiazepines was associated with an increased risk of death from drug overdose. BMJ, 2015 Jun 10;350:h2698

Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. Leung A, Shukla S, Fallah A, Song D, Lin L, Golshan S, Tsai A, Jak A, Polston G, Lee R. TMS treatment significantly reduced the intensity of headaches (by 50 percent) among Veterans with headaches related to mild traumatic brain injury as compared to the control group. Neuromodulation. 2015 Nov 10. (Epub ahead of print.)

Endomorphin analog analgesics with reduced abuse liability, respiratory depression, motor impairment, tolerance, and glial activation relative to morphine. Zadina JE, Nilges MR, Morgenweck J, Zhang X, Hackler L, Fasold MB. Endomorphin analogs could provide gold-standard pain relief, but with remarkably safer side effect profiles compared with opioids like morphine. Neuropharmacology. 2015 Dec 31;105:215-227.

Prescription opioid duration, dose, and increased risk of depression in 3 large patient populations. Scherrer JF, Salas J, Copeland LA, Stock EM, Ahmedani BK, Sullivan MD, Burroughs T, Schneider FD, Bucchols KK, Lustman PJ. Patients and practitioners should be aware that opioid analgesic use of longer than 30 days imposes risk of new-onset depression. Ann Fam Med, 2016 Jan;14(1):54-62.

Opioid dose and risk of suicide. Ilgen MA, Bohnert AS, Ganoczy D, Bair MJ, McCarthy JF, Blow FC. The risk of suicide mortality was greater among individuals receiving higher doses of opioids, and treatment providers may want to view high opioid doses as a marker of an elevated risk for suicide. Pain, 2016 Jan 5. (Epub ahead of print.)

Distribution of opioids by different types of Medicare prescribers. Chen JH, Humphreys K, Shah NH, Lembke A. Most prescriptions for opioid painkillers are made by the broad swath of U.S. general practitioners, not by a limited group of specialists. JAMA Intern Med. 2016 Feb 1;176(2):259-61.

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