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What is Chronic Pain?
In 1931, the French medical missionary, Dr. Albert Schweitzer wrote, “Pain is a more terrible lord of mankind than even death itself.” Today, pain has become a serious and costly public health issue, and it remains largely under-treated and misunderstood. According to the National Institutes of Health, 90 million people in the U.S. suffer from chronic pain. The American Pain Foundation estimates that chronic pain is the cause of $100 billion a year in lost work time and health care.
The scope of individuals enduring some type of pain even eclipses cardiovascular disease, the nation’s number one killer of adults. By comparison, the American Heart Association reports that 71 million Americans suffer from cardiovascular disease.
The National Pain Foundation (www.nationalpainfoundation.org), a health advocacy group for pain sufferers, notes that one in four people in the United States suffers from chronic pain and more than 40 million physician visits every year are related to pain. Yet, when individuals complain about pain, they are often given inadequate treatment or, out of strong fear of medications or aggressive therapies, they simply give up and decide to live with their pain.
Types of Chronic Pain
When pain lasts for a long time, it is considered to be chronic pain. Many physicians consider pain to be chronic when it has lasted for six months or longer. Others say that pain is chronic when it lasts one month longer than would generally be expected considering the injury, surgery, or disease that is causing it.
To understand chronic pain, it can be helpful to categorize pain in general. Basically, there are two types of pain: nociceptive and neuropathic.
Nociceptive Pain
Nociceptive pain is caused when special nerve endings—called nociceptors—are activated. This type of pain results from an injury to the body (such as a cut or burn), surgery, or a disease that is not a part of the nervous system (like arthritis or cancer). Pain from the activation of nociceptors depends on the parts of the body involved. It can be felt as a localized sharp, aching, or throbbing pain that is constant, or it can be a generalized deep, aching pain that comes and goes.
Neuropathic Pain
Neuropathic pain is caused by a malfunction of the nervous system due to injury, disease, or trauma. It can be sharp, intense, and constant, usually felt as a burning, shooting, or tingling pain; it can also be sporadic and felt as a dull, aching, and throbbing pain (for example, the chronic pain that people experience in their lower backs, upper backs, and legs is usually of this type). Neuropathic pain is divided into two categories: simple and complex. Simple neuropathic pain usually involves a single extremity such as an arm or leg, while complex neuropathic pain usually involves multiple extremities and has the possibility of spreading.
Because chronic pain can arise spontaneously without a known cause and can vary widely in intensity, location, and response to therapy, treating it successfully can be a major challenge. Not treating it or under-treating it, however, can be devastating.
Treatment Approaches
Chronic pain has been under-treated in part because the traditional practice of medicine was to focus on an underlying disease and not its symptoms. However, as pain came to be considered by many to be, itself, the disorder, a newer branch of medicine has evolved that deals specifically with pain management. Now, many physicians and clinicians realize just how important it is to treat pain in order to fully meet their patients’ desire to live fuller, more active lives. And, on their part, patients are becoming more involved in their treatment and are requesting pain relief therapies from their doctors.
Pain is a reaction to signals transmitted from a pain source that travel through the nerves in the spinal cord to the brain. This means that pain can be controlled by interrupting or modulating the pain signals before they reach the brain.
Most individuals who develop a chronic pain condition try several types of therapies in their search for relief. Typically, they begin with conservative measures such as exercise, over-the-counter medications, rehabilitative therapy, transcutaneous electrical stimulation, and cognitive and behavioral modification.
When these treatments fail to work, physicians may prescribe more aggressive pain therapies such as nerve blocks, which use a chemical blocking agent, or neurolysis, which physically destroys nerve tissues. Prescription pain medications (systemic opioids) are frequently introduced at this stage; however, negative side effects, including dependency, can result.
When chronic pain conditions resist these therapies, patients may require more advanced treatment options. Surgery, implantable drug pumps, or neuroablation (a permanent surgical technique that blocks pain by destroying nerves and tissues at the source of the pain) may be recommended to combat chronic pain. Neurostimulation is an advanced alternative that pain practitioners also may offer their patients. This therapy includes spinal cord stimulation (SCS) systems that interrupt the pain signals on their way to the brain.
Patient Resources
Patients should always be encouraged to talk with their physicians or seek out pain management practitioners if they believe they are suffering from chronic pain.
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Spinal Cord Stimulation Shows Success in Cancer Pain
Linda Pembrook
SAN FRANCISCO—Spinal cord stimulation (SCS) has shown efficacy in the treatment of cancer pain, but it is important to prepare the patient, family and oncologist to have realistic expectations, said Sunil J. Panchal, MD, president of the COPE Foundation in Tampa, Fla. The technique should not be used to treat patients with an active tumor, and for some patients, the treatment may need to be converted to an intrathecal infusion system or an ablative therapy.
“Provide [the patient with] specific printed information in terms of what to do and where to go,” he recommended in a presentation at the 2006 annual fall meeting of the American Society of Regional Anesthesia and Pain Medicine. “Advise patients to pursue CT [computed tomography] first.”
The importance of pain management following surgery in cancer patients was demonstrated in a follow-up study of thoracotomy patients, in whom the incidence of persistent pain was 80% at three months and 61% at 12 months (Acta Anaesthesiol Scand 1999;43:563-567). In a study of 511 patients undergoing mastectomy, 43% experienced chronic postsurgical pain (Clin J Pain 2004;20:70-75).
SCS has shown excellent results in some trials, Dr. Panchal said. For example, a recent clinical case report described two patients with chemotherapy-induced neuropathy whose pain scores improved and who were able to reduce their use of medication after SCS (J Pain Symptom Manage 2004; 27:72-78).
“It is very easy to get adequate coverage from a paresthesia perspective and to treat neuropathic symptoms. But there is no good literature in this area—almost everything comes down to consensus or expert opinion,” Dr. Panchal said.
Case Studies
Referring to his own practice, Dr. Panchal described the case of a 52-year-old man with a right-sided Pancoast tumor that was in remission. The patient developed brachial plexitis after undergoing radiation therapy. He did not obtain adequate pain relief from multimodal pharmacotherapy and experienced side effects from this treatment. The patient reported good short-term relief after a stellate ganglion block was performed by another physician.
“With spinal cord stimulation, he was able to significantly reduce his opioid consumption while maintaining his gabapentin regimen. After two years, he has continued good control and coverage. We didn’t see any migration of the SCS system.”
Dr. Panchal also described a 56-year-old woman with pain after thoracotomy who experienced significant sedation with low-dose opioids and was looking for a nonpharmacologic alternative. Since undergoing SCS, she has had good pain relief for 18 months and has stopped using opioids, with no recurrence of tumor, he said.
In another case, a 58-year-old woman who underwent thoracotomy two years earlier obtained good relief with dual-lead SCS, but the SCS system migrated six weeks after implantation. With revision, she has had continued relief for 18 months and has reduced her opioid consumption by about one-third, Dr. Panchal said.
“Typically, with thoracotomy patients, we will place one lead just off midline and the second lead a little further later, almost into the gutter,” Dr. Panchal explained. “My ability to get adequate coverage of paresthesia all the way around the chest wall has improved recently with the advent of stimulator leads with tighter spacing and the increased sophistication of the programming systems.”
MRI Warning
If magnetic resonance imaging (MRI) is considered for a patient with an implanted device, estimation of the risks and benefits is essential, Dr. Panchal said. Medtronic makes specific safety recommendations, for example, that patients with SCS should not undergo MRI using a full-body transmit radiofrequency (RF) coil, a receive-only head coil or a head transmit coil that extends over the chest area.
Several factors can increase the risks for heating and patient injury, including the following: a high MRI-specific absorption rate, the use of low-impedance leads or extensions, a transmit/receive coil that is near or extends over the implanted lead system, implanted lead systems with small surface-area electrodes, and short distances between lead electrodes and heat-sensitive tissue.
MRI was safely performed in a study of 38 patients with implanted neurostimulators (Neurosurgery 1999;44: 118-125). The study authors concluded, “There is no danger with any type of electrode during MRI examinations if the electrodes lie outside the region of interest,” but they noted that the findings are restricted to the two types of devices tested in this study. In contrast, a recent case report described a patient with Parkinson’s disease in whom permanent neurologic injury developed secondary to an RF lesion produced by heating of a deep-brain-stimulation electrode during MRI of the lumbar spine (Neurosurgery 2005;57:E1063).
Another case report concerned a patient with complex regional pain syndrome in whom a conversion disorder—partial paralysis—developed after implantation of an SCS system (Anesth Analg 2003;96:201-206).
Robert Plunkett, MD, associate professor of neurosurgery at the University at Buffalo School of Medicine and Biomedical Sciences in New York, agreed that SCS has a limited role in the treatment of cancer pain, and that basically it is used to treat patients with pain after thoracotomy or neuropathic pain related to chemotherapy or radiation therapy.
“In these cases, you need to do a trial of spinal cord stimulation to understand if that patient is going to be a responder before you put in a permanent system,” Dr. Plunkett said. “In those groups, probably 60% to 70% will be responders and 30% will be nonresponders. If they don’t respond, you move on to a different technique, such as intrathecal narcotics or other intrathecal agents.”
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Pain Rehabilitation Provides Lasting Cuts in Drug Costs
Pain specialists seeking hard evidence to support the economic argument for pain rehabilitation programs now have a study to cite. Researchers have shown that patients with chronic pain who complete a three-week outpatient rehabilitation program can significantly reduce their daily medication costs. These savings can be maintained for at least six months, the researchers found.
“As the saying goes, ‘He who has the gold makes the rules,’” said Dennis C. Turk, PhD, professor of anesthesiology and pain medicine at the University of Washington in Seattle. “The gold is being held by third-party payers, and they want to know what kind of savings they will see” before approving a program.
Although previous studies extrapolated financial data from other end points—hospitalization rates, surgery rates and changes in disability payments—the latest work is among the first to show direct cost savings, Dr. Turk said.
The initial study population included 177 adults who were consecutively admitted into the rehabilitation program between June 2005 and January 2006. Patients were primarily female (80%), white (95%), married (63%) and had a mean of 14.8 years of education. Primary pain diagnoses included low back pain (25%), fibromyalgia (21%) and chronic headaches (11%).
“This is a population with very chronic pain,” said lead study author Julie L. Cunningham, PharmD, of the Mayo Clinic Department of Pharmacy, in Rochester, Minn. Patients entered the program after having endured pain for a mean of 9.4 years; 53% reported daily use of opioids upon admission. Only 39% of program participants were full-time Minnesota residents; 61% of patients attended the rehabilitation program from other states, said Dr. Cunningham, who presented her findings at the 2008 annual meeting of the American Academy of Pain Medicine (abstract 153).
The outpatient program provided a range of services, including physical and occupational therapy, sleep hygiene, anger management and education on medication use and the cycle of chronic pain. On admission, a pharmacist took a detailed history of prescription and over-the-counter medications, including tablet size and frequency of administration, and calculated the average wholesale price of daily medications.
The medication survey was repeated after three weeks, and again at six months. With the exception of medications requiring complicated tapering, all drugs were self-administered during and after the outpatient program. The analysis included data from the 112 patients who completed the six-month follow-up survey.
“We saw more than a 30% reduction in medication costs at both time points,” Dr. Cunningham said. During the three-week program, mean medication costs dropped by $8.63 per day, from $23.66 at admission to $15.03. At six months, mean daily medication costs were $15.99—a cost savings of $7.77 from admission (P<0.05; Table).
Table. Daily Medication Costs at Admission,
Program Completion and Six-Month Follow-up
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Daily Medication Cost,
Mean AWP (SD) Cost Savings Versus Admission,
Mean (SD)
Admission $23.66 ($17.25) —
Program completion $15.03 ($12.21) $8.63 ($12.00)
Six-month follow-up $15.99a ($13.97) $7.77 ($14.56)
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a P < 0.05 versus admission.
AWP, average wholesale price; SD, standard deviation
Not every patient experienced a savings in medication costs during and after the program. One patient had no change in medication costs, and 35% reported increases in daily medication costs of $20 or less. Still, nearly two-thirds of the patients had some cost savings during and after the program, some more than $30 a day. Medication costs did not include nonprescription topical, parenteral, inhalational, ophthalmic or intrathecal agents.
A full pharmacoeconomic analysis should include the costs of the three-week rehabilitation program, which the Mayo researchers did not calculate, Dr. Turk noted. In addition, he said, independent confirmation of these findings would be necessary to provide further economic justification for pain rehabilitation programs.
Still, Dr. Turk said, the study “confirms that medication is expensive and frequently used in this population, and that rehabilitation programs can bring significant cost savings.” For payers, he said, a 30% reduction in medication costs that is maintained over time may be a more meaningful end point than reductions in self-reported pain.
—Anne Jacobson
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Stimulating Discussions
Researchers Review the How of Neuromodulation for New Indications
Rosemary Frei MSc
Clinical researchers continue to open new avenues for the use of deep brain and spinal cord stimulation, treating conditions from Parkinson’s to angina. But the mechanisms of action of neuromodulation may be mysterious to many clinicians, particularly in the newer applications of stimulator devices.
At the 2007 annual meeting of the North American Neuromodulation Society, in Acapulco, Mexico, two experts presented overviews of how nerve stimulation seems to work for some of the newest applications of the electrical treatments.
Robert Foreman, PhD, professor of physiology at the University of Oklahoma Health Sciences Center in Oklahoma City, gave an overview of the field dating back to his team’s 1976 demonstration of electrical inhibition of pain perception in the spinothalamic tract by stimulation of the dorsal columns (J Neurophysiol 1976;39:534-546). Dr. Foreman also discussed much more recent work showing that spinal cord stimulation (SCS) improves the function of both peripheral structures and visceral organs.
For example, Dr. Foreman noted, SCS can improve peripheral blood flow in people suffering from peripheral vascular disease. It does so by stimulating release of calcitonin gene-related peptide, a protein that both dilates blood vessels directly and stimulates the production by endothelial cells of nitrous oxide, a potent vasodilator.
SCS also appears to have many beneficial effects on cardiac function, primarily by enhancing blood flow in the organ. The treatment is approved for refractory angina in the European Union, but not in the United States.
“Spinal cord stimulation doesn’t mask pain, as was originally believed, but rather it directly improves the function of the heart,” said Dr. Foreman, a member of the International Working Group on Neurocardiology. “It stabilizes the cardiac nervous system and makes the patient feel much better.”
In addition, SCS has been shown to blunt the nociceptive reflex in an animal model of acute hypersensitivity in the gastrointestinal tract. Such an effect, if demonstrated in humans, could prove helpful in the treatment of postinflammatory irritable bowel syndrome and related conditions (Auton Neurosci 2005;122:69-76).
“We created an animal model with a hypersensitive colon, and we saw that there was a marked decrease in abdominal muscle contractions—a nociceptive reflex—with the use of spinal cord stimulation,” Dr. Foreman said. “Therefore, in irritable bowel syndrome in humans, there would be a reduction in the hypersensitive effects of the colon and hence an amelioration of the patients’ symptoms.”
Jeffrey Arle, MD, PhD, director of functional neurosurgery at the Lahey Clinic in Burlington, Mass., called the presentation “compelling” and predicted it would “further broaden awareness of the ever-enlarging potential of neural interfaces in general.”
Overriding the Current
Warren Grill, PhD, associate professor of biomedical engineering at Duke University, in Durham, N.C., has focused in the last decade on elucidating how deep brain stimulation (DBS) works in people with movement disorders, including essential tremor and Parkinson’s disease.
His team’s research is generating evidence that DBS overrides the abnormal pattern of electrical activity in the nerve cells, and replaces it with a regular pattern at the same frequency as the stimulation.
He and his colleagues first documented that DBS creates an “informational lesion” in the stimulated nucleus in the brain (Neuroreport 2004;15:1137-1140). Within this zone, intrinsic activity is suppressed and replaced by constant-rate neuronal firing.
Dr. Grill and his co-investigators published three papers in 2007 that delved more deeply into the effects of DBS by combining computational models with experiments in human subjects with the devices.
In one study, they confirmed a strong correlation between the ability of DBS to regularize neuronal firing and its ability to suppress tremor (IEEE Trans Neural Syst Rehabil Eng 2007;15:190-197).
In a second paper, they corroborated, by use of computer models and examination of patients with essential tremor, that high-frequency stimulation is insufficient for DBS to be effective. Rather, they found that the pulses must be regular for the treatment to succeed (J Neurophysiol 2007;98:1675-1684). The third paper summarized the accumulating evidence that DBS suppresses abnormal patterns of neuronal activity and replaces them with regular, constant-rate firing (Neurotherapeutics 2007;5:14-25).
“What’s quite remarkable is that we are replacing one abnormal pattern of activity—in this case burst firing in neurons, which had been giving rise to movement disorders—with a new pattern of activity, which is also abnormal and yet which results in symptom relief and significant improvement in voluntary control of movement,” Dr. Grill said.
Dr. Arle called Dr. Grill’s work critical to understanding the theoretical scaffolding for the efficacy of DBS, and perhaps that of other neuromodulation techniques as well.
“This is a line of inquiry—computational approaches—that may be the only means to understand the underlying mechanisms of DBS, since it may never be possible to record from every, or most, cells simultaneously while stimulation is occurring without destroying the tissue itself,” Dr. Arle said. “It may ultimately become a part of further knowledge that has real clinical implications in terms of electrode or programming design, or even target selection in DBS.”
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