New developments in pain management.

Thursday, December 6, 2007 | 0

By Steven Feinberg, MD

The following are all relatively new and interesting developments in pain treatment. Some represent possible successes in pain treatment, and others provide new information about possible problems or side effects from certain treatments.

It is important to remember that new developments have not withstood the test of time, during which more revealing research may be conducted. Nevertheless, it could be important for people with chronic pain to consider these new developments as they make treatment decisions.

<b>Medications for Pain</b>

Duloxetine (Cymbalta) for neuropathic pain: The antidepressant duloxetine has demonstrated benefits for people with some forms of neuropathic pain. It is FDA approved for painful diabetic neuropathy and it has shown efficacy in fibromyalgia but is not FDA approved for it. Research has not been published on the effectiveness of duloxetine for other types of neuropathic pain, musculoskeletal (i.e. arthritis), or visceral pain, like interstitial cystitis. It is important to note that although duloxetine and related drugs are referred to as antidepressants, recent evidence does suggests that it may have direct analgesic effects beyond its antidepressant benefits.

Pregabalin (Lyrica) for managing fibromyalgia: On June 21, the anti-seizure drug pregabalin (Lyrica)  was approved by the FDA for the management of fibromyalgia syndrome. The agent is also approved for the management of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia, and in epilepsy for the adjunctive treatment of partial onset seizures in adults. Pregabalin not only appears to improve pain in persons with fibromyalgia, but it also has a broader effect on improving function. According to a randomized, placebo-controlled trial (abstract 695) presented at the 2007 annual meeting of the American Pain Society Recent studies show pregabalin efficacious for central pain (brain or spinal cord injuries) and pain after surgery.

Possible new risks with chronic use of PPIs: Many people with pain take non-steroidal anti-inflammatory agents (NSAIDs). Because of heartburn, ulcers, and other gastrointestinal problems, their doctors also prescribe the use of acid-suppressing proton pump inhibitors (PPIs) for prevention and treatment. A study published in 2006 raised concerns because the chronic use of PPIs might have a significant impact on the rate of hip fractures. The authors think that acid-suppressive therapy may be increasing the risk of hip fracture by decreasing calcium absorption. Thus, as with all medications, PPIs must be used with caution and the disadvantages must be weighed against the benefits.

Possible Treatments for CRPS: It has been suggested that N-methyl-D-aspartate (NMDA) receptors may play a role in clinical chronic neuropathic pain, including complex regional pain syndrome (CRPS), also known as reflex sympathetic dystrophy (RSD). If this is true, then it is possible that blocking NMDA receptors would be beneficial. The utility of these agents has been limited by their significant side-effect profile, which includes lightheadedness, dizziness, tiredness, headache, nervous floating sensation, bad dreams, and sensory changes. Drugs that have clinically relevant NMDA-blocking properties include ketamine, amantadine, memantine, dextromethorphan, and methadone. The concept of NMDA blocking in neuropathic pain is reasonable but there is a strong need for more research and perhaps development of newer agents with fewer central nervous system side effects.

Recently, there has been significant interest in the use of thalidomide as a treatment for CRPS. This is based on the possible role played by natural chemicals found in the body called inflammatory cytokines, which thalidomide inhibits. There are no published clinical trials on thalidomide use in CRPS, only case reports demonstrating benefit. The drug is currently being studied in clinical trials, but because of its history of causing birth defects, women of childbearing age have been excluded, and extensive monitoring is required.

Bisphosphonates (e.g., pamidronate, clodronate, and alendronate) inhibit calcium bone resorption and have demonstrated some benefit in the treatment of CRPS in several studies. Still further research is needed. The data on bisphosphonates looks promising for CRPS but side effects are a major concern.  Topical DMSO (dimethyl sulfoxide) 50% and oral NAC (N-acetylcysteine) recently were shown to possibly have some benefit in CRPS but there is no scientific evidence as yet to support its use.

Concerns about Long-term Use of Opioid Analgesics: While opioid (narcotic) analgesics have been the mainstay for treating chronic intractable pain for quite some time, there are growing concerns about the long-term use of high dose opioids.

The problem with long-term reliance on opioids is that prolonged use may heighten the risk of accidental death from respiratory depression (although most people do become tolerant to the respiratory depressive effects) It can also result in problems including tolerance, hyperalgesia (abnormal pain sensitivity), hormonal effects (decreased testosterone levels, decreased sex drive and irregular menses), depression, and suppression of the immune system. While opioids may initially be prescribed to reduce pain and hopefully improve function, the treatment may actually produce the opposite result.

The exact relationship between higher opioid dosage and risk is not yet clear, but a troubling pattern of increased numbers of deaths associated with prescription opioid use has emerged during the same period that average dose size has significantly increased.

Respiratory depression (a reduced drive to breathe) with opioid use is a serious concern. It can be fatal when doses are increased rapidly or in opioid naïve persons In addition, opioids become particularly dangerous when used in conjunction with alcohol or with other medications that can worsen respiratory depression—sedative-hypnotics, benzodiazepines, anti-depressants, and muscle relaxants.

Pros and Cons of Implantation Technologies: The technology and equipment for spinal cord stimulators and implanted pumps continues to improve. The manufacturers claim wider and better coverage and there are now rechargeable batteries thus lengthening the time between the need for surgical replacement. However, the technology remains expensive Some medical professionals question the long-term gains and don’t feel the technologies have been adequately proven beneficial. Proponents note evidence of cost savings over time although long-term data on lasting effectiveness is lacking.

Ziconotide (Prialt), administered by an implanted pump, is a therapeutic option for treatment of severe chronic pain in persons who have exhausted all other agents, including morphine by an implanted pump, and for whom the potential benefit outweighs the risks of serious neuropsychiatric adverse effects and of having an implanted device. This drug is not benign and before being utilized, a careful consideration should be given to the benefits versus potential negative side effects.

Hyperbaric Oxygen Shows Promise: Hyperbaric oxygen (HBO) therapy recently has shown promising results for some chronic pain syndromes but its use is far from proven. Several authors claim HBO is a reliable method of treatment and may be beneficial if appropriate persons are selected. Further research is required to identify the best treatment protocol, the cost/benefit ratio, and the safety of HBO in chronic pain management—and whether it actually works.

Functional Magnetic Resonance Imaging: While still in its infancy in the research lab and not yet ready for clinical practice, Functional Magnetic Resonance Imaging or fMRI offers hope for people with persistent pain.  Experts believe that fMRI can be used to show people what areas of their brains are activated when they’re in pain. They could then be taught techniques for turning off, or at least turning down, their brain-initiated pain. The rationale for fMRI as a treatment is similar to biofeedback, whereby people with pain associate abnormal physical functioning (muscle tension, constricted blood vessels) with signals, like sound or lights, that they may be able to learn to control.  An interesting article on this subject, The Strain in Pain Lies Mainly in the Brain, by Sean Mackey MD, PhD, Director of Stanford University’s Pain Management Center, can be found at  http://paincenter.stanford.edu/research.

Neurofeedback (EEG Biofeedback): One case report and a case series have reported that chronic pain can be reduced through electroencephalogram (EEG) biofeedback (also known as neurofeedback). It has been used to teach people with chronic pain to decrease the type of brain activity associated with pain and increase the type of brain activity associated with relaxation in order to reduce their pain. But controlled studies showing that this treatment is more effective than placebos have not yet been performed.

Lumbar Disc Replacement: There continues to be great interest in surgical replacement of lumbar discs. It has been widely used in Europe and is becoming more popular in the United States. There are strong proponents who tout its benefit while others question its relative effectiveness and long-term efficacy compared to rehabilitation programs.

The Biopsychosocial Model of Functional Restoration: One of the new changes in pain treatment is really very old, well-researched, and well-established. It is as much philosophical as anything else. There is a growing rebirth and revitalization in pain treatment of the biopsychosocial model and the concept of functional restoration.

The traditional approach, termed the biomedical model, views pain as being directly caused by a specific injury or disease and treatments are designed to correct physical pathology or to cut or block the pain pathways either by drugs or invasive procedures such as surgery or nerve blocks. While this model seems to work with acute and some chronic disease states, these approaches often result in inadequate pain relief and unacceptable levels of disability that persists well after the original injury has stabilized or healed. There are also side effects associated with all of these treatments that may actually require additional treatments and in some instances result in even greater pain.

The biopsychosocial model uses a functional restoration approach. It recognizes that pain is ultimately the sum of the person's:              

    * Medical condition
    * Psychological state
    * Cultural background/belief system; and
    * Relationship/interactions with the environment such as the workplace, home, disability system, and medical providers.   

In the biopsychosocial model the focus is on the person not the disease or physical pathology. Appropriate treatment in this functional restoration model includes assessment of the person’s dynamic physical functional status. Along with traditional tests for strength, sensation, and range of motion are measures of what the individual can and cannot do functionally in terms of activities of daily living and in terms of work-related functions. The assessment reviews psychosocial strengths and weaknesses including an analysis of the individual’s support system. It also includes efforts at education of the individual and family members along with expectation management, functional goal setting, ongoing assessment of the individual’s participation and compliance, complicating problems, and progress toward achievement of goals.

There is now evidence from a number of controlled trials that one of the components often used in biopsychosocial treatments, self-hypnosis training, can reduce pain severity in some (but not all) individuals with chronic pain, and that these reductions can last at least 12 months (the length of follow-up from these studies).  Even though not everyone reports a long-lasting reduction in their pain with this treatment, the majority report that once they learn self-hypnosis techniques, they can use them to obtain short-term reductions in pain that last for hours.

Functional restoration and pain management skill training includes a focus on education, a de-emphasis on passive therapies, with importance placed on a home exercise/self-management effort. There is a shift of health and well-being responsibility (locus of control) from the doctors and therapists to the person. A substantial body of research has supported the benefits of this approach not only in pain reduction but improvement in physical and emotional functioning. This also results in less utilization of health care with few, if any, adverse events.                                           
 
<i>Dr. Steven Feinberg is a physician and QME at the Bay Area Pain & Wellness Center in Los Gatos. He is a Diplomate of the American Board of Physical Medicine and Rehabilitation, the American Board of Pain Medicine and the American Board of Electrodiagnostic Medicine. </i>