By Forest Tennant MD, MPH, DrPH
There is a magnificent and caring history surrounding the treatment of intractable pain patients. While the name intractable may not have been used, historical descriptions of persons with this type of pain make it clear that they had constant, incurable pain. This is the basic definition of “intractable.”
Dr. John Fothergill was the esteemed British physician in the 1700s who tackled the intractable pain of incurable, terminal tuberculosis with a concoction of opium and alcohol. My rendition of these events ended when I started the first public health facility in 1975, to treat both persons who were addicted to the opioid heroin, and those who had intractable pain.
Two very important precepts historically stand out. Some caring and diligent physicians believed that no one should have to suffer or die in intractable pain. The other precept is that life should not be shortened by depriving any intractable pain patient of opioids or other pain-relieving drugs. It has been well-known among physicians over the past two centuries that severe, untreated pain shortens life.
John Fothergill was the preeminent physician in London during the 1700’s. He was the first to recognize and publish that pain could best be treated with a combination of opium and alcohol. His formula for the pain, cough, and depression of incurable, fatal tuberculosis (called consumption) was “one-half ounce of pure white opium seeds in a pint of Bristol.” This concoction established the scientific principle that opioids should be combined with a “potentiator” for maximum effect. Opium and alcohol combinations were used for war wounds by the physicians under the command of George Washington in the Revolutionary War.
In the 1800’s “Doc” Holliday was a dentist who became famous as a gunfighter in Dodge City, Kansas, and Tombstone, Arizona including the “shoot-out” at the OK Corral. He had a lung disease believed to be tuberculosis or a related disease, and he used a combination of opium and alcohol for pain relief. Because of his medical knowledge of medicines, he was probably able to live much longer than would have been expected for a person with his condition.
A major advance in the treatment of intractable pain was the development of a syringe that could inject morphine. Although various injection syringes were initially made, it was the Scottish physician Alexander Wood, who in 1853, first combined a hollow steel needle with the proper syringe that could inject morphine into a human.
The first concerted attempt to treat intractable pain in the United States was to relieve the pain caused by neurologic injuries incurred by soldiers in the Civil War. Soldiers particularly developed severe pain in their arms, legs, and feet. This pain was called “causalgia.” Today it is known as reflex sympathetic dystrophy (RSD), or complex regional pain syndrome (CRPS). Morphine was given to injured soldiers, in many cases, for several years after the war.
In 1896, physicians at the Brompton Hospital in London, England began treating severe intractable pain. They discovered that opioids should be mixed with stimulants for maximal effect. Their original mixture contained morphine and cocaine. Later it was called the “Brompton Cocktail.” The Brompton Hospital formulary in 1957 listed these ingredients: Morphine hydrochloride, ¼ grain(15mg), Cocaine hydrochloride, 1/6 grain (10mg), Alcohol 90% (2ml), Syrup, 4ml, Chloroform water, ½ Fl. (15ml).
The Federal Medical Center in Lexington KY opened on May 15, 1935, on 1,000 acres under the name “United States Narcotic Farm.” The name was later changed to the “US Public Health Service Hospital.” In 1967, it changed its name again to “National Institute of Mental Health, Clinical Research Center.” Its original purpose was to treat people who voluntarily were admitted with drug abuse problems to treat them, mostly with experimental treatments. It was the first of its kind in the United States. The site included a farm where patients would work. Although initially opened for volunteers, it later became a facility where addict prisoners were sent. In 1974 the “Farm” was closed as a therapeutic center for drug addicts, and in 1990 it was declared a Federal Medical Center for seriously ill Federal prisoners. Before 1976, within the hospital was a research unit to find addiction treatments as well as non-addicting pain treatment drugs. After World War II, narcotic formulas were taken from the Germans and tested at the center. Part of the testing was the administration of test drugs to hospitalized addicts. This research program developed methadone and other opioid-related compounds that are currently used today. Physicians who staffed the hospital were public health physicians and established the notion that addiction and intractable pain should be treated by such physicians. Consequently, physicians who started addiction and intractable pain treatment in America’s cities in the 1970s were, like the author, trained public health physicians. *
The Public Health Facility in West Covina, California (East of Downtown Los Angeles) was established in 1975. The clinic was upstairs over a row of commercial establishments. The center was initially located and financed through the Los Angeles County Public Health Foundation. It was directed by the author who had just obtained his doctorate in public health. The facility provided standard public health services for tuberculosis, sexually transmitted diseases, vaccinations, family planning, and well-baby care. A methadone clinic for heroin addicts was started as well as an intractable pain program. The first intractable pain patients were either referred from the regional cancer hospital (City of Hope) or were desperate, non-addict intractable pain patients who had heard that methadone had become available to treat their pain.
Dr. Frank Fraser became a research physician in 1949 at the Federal Narcotic Facility in Lexington, Kentucky. He developed methodologies to test and determine the addiction and pain relief potential of many compounds. Testing included the administration of drugs to inmates. A major discovery by Dr. Fraser was drugs that are technically called mixed agonist-antagonist compounds which provide good pain relief with limited addiction potential. His methods led to the development of pentazocine and today’s buprenorphine. After 1963 he became a research consultant for Eli Lilly and the Federal research agencies concerned with addiction and pain relief. When the author began to develop the Nation’s first outpatient facility in 1975, Dr. Fraser was sent by his sponsors to West Covina, CA on several occasions to consult with and train the author. At that time, Dr. Fraser possessed more knowledge of addiction and pain than any other physician in the United States, and he believed that only physicians who understood the difference between opioid addiction and intractable pain should attempt long-term treatment with narcotics.
Dr. Vincent Dole (1913-2006) along with his wife, Dr. Marie Nyswander (1919-1986), were the physicians who developed the use of methadone to treat heroin addiction. Both were originally research physicians at the Federal Narcotic Facility in Lexington, Kentucky. They were recruited away to New York in the early 1960’s by the Rockefeller Foundation to find a treatment for heroin addiction which was plaguing New York and other metropolitan areas. The author became aware of their work and administered methadone to addicted US Army soldiers when he served as a US Army Medical Officer in Germany in the late 1960s. Although these physicians are best known for their addiction efforts, they also established how intractable pain should be treated. They both shared the belief that heroin and other opioid addictions had a genetic, irreversible makeup, that often required methadone to suppress their craving for opioids. Drs. Dole and Nyswander believed that intractable pain should be treated with a low, daily dose of methadone since it was long-acting. Pain flares, or what they called “breakthrough” pain, were treated with a short-acting opioid. This procedure was primarily used for intractable pain until the commercial development of the fentanyl patch and long-acting oxycodone (Oxycontin®). These were initially, (and many believe falsely), promoted for superior intractable pain treatment compared to the “methadone/short-acting opioid” protocol. It is noteworthy that Dr. Dole received the distinguished 1988 Albert Lasker Award for Clinical Medical Research.
In 1972, when the author was transferred from the US Army Medical Corp to the United States Public Health Service as an Academic Fellow, he spent time training with Dole and Nyswander at the Rockefeller Center to learn their methods of treating both opioid addiction and intractable pain. It was the general belief of Dole and Nyswander, in the 1970’s and 80’s, that public health physicians should be the primary physicians to use opioids in the treatment of both addiction and intractable pain.
Dr. Houde was a physician who specialized in treating cancer pain. While at Sloan-Kettering Hospital in New York, he developed the concept of morphine equivalence. His table of morphine potency was to assist physicians when they needed to change opioids. The concept of morphine potency or equivalence has recently been adopted to regulate and restrict opioid use, which was never even considered or intended by Dr. Houde. It was strictly a clinical tool. The author was mentored by Dr. Houde in the first years of his intractable pain clinic as the focus was greatly on treating late-stage or post-cancer patients. These patients often suffered pain from tissue destruction of the cancer and surrounding tissue by mutilating surgery or radiation. Dr. Houde believed that opioid dosages should be titrated upward, over time, regardless of dosage to ensure pain relief and allow the patient to maintain mental and physical function. He firmly believed that no one should die in pain, or that life should be shortened by deprivation of opioids.
Dr. Elizabeth Kubler-Ross (1926-2004) championed end-of-life care and admonished other physicians to have open and honest conversations with patients about death and dying. The author started his original clinic in 1975, in part, to emulate Dr. Kubler Ross in the care of end-of-life patients. He surprisingly found that some end-of-life patients with intractable pain could prolong their lives by months or years if they were treated with a combination of opioids and stimulant drugs.
Dr. Murad “Jack” Kevorkian (1928-2011) was an American pathologist and euthanasia proponent. He publicly championed a terminal patient's right to die by physician-assisted suicide, embodied in his quote, “Dying is not a crime.” He was the first and most famous physician to advocate and practice assisted suicide. Dr. Kevorkian contacted the author and said he had patients who didn’t wish to die if they could only get intractable pain care. Consequently, some referrals were accepted by the author from Dr. Kevorkian, and they lived for several more years with intractable pain care.
Dr. C. Stratton Hill, Jr. (1928-2015) was the Texas physician who sponsored and lobbied the Texas Legislature to pass the first intractable pain law in 1990. The law intended to allow physicians to prescribe opioids to bona fide, intractable pain patients without fear of prosecution by State Medical Boards and Departments of Justice. Intractable pain was defined as “incurable by any known means.” Dr. Hill had been president of the Texas Medical Association and was an expert in treating cancer and other causes of intractable pain. He obtained the definition of intractable pain and criteria for the necessity of opioids from the work and publications of the former work of the British Intractable Pain Society.
Shortly after Texas passed its Intractable Pain Act in 1990, Dr. Harvey Rose (1932-2008) and State Senator Leroy Greene (1918-2002) lobbied the California Legislature and Governor to pass an Intractable Pain Act that was essentially identical to the Texas Act. Along with the author, Dr. Rose and Senator Greene later convinced the California Legislature to enact the California Pain Patients’ Bill of Rights in 1998. These legislative achievements fostered a significant movement of research and treatment of intractable pain for the following twenty years.
In 1972, the author was transferred from the United States Army Medical Corp to the United States Public Health Service and assigned to the UCLA School of Public Health as an Academic Fellow. At that time, he met Dr. Joel Hochman, who was a psychiatric resident. Both of us immediately became friends and colleagues as we believed that addiction, alcoholism, and intractable pain were emerging as dominant public health issues. This mutual belief led our colleagues to brand us as “misguided mavericks.” Dr. Hochman went on to become an expert in intractable pain management, leading him to establish the National Foundation for the Treatment of Pain in 1998. As a tireless and powerful advocate for the rights of others to be free from needless suffering, he fought and won many regulatory battles on their behalf at times under grave pressure and unrelenting adversity. Clinically, he believed that opioid dosages should be titrated upward over time to a point that pain was relieved and biological functions were retained so the patient should have a good quality of life.
Dr. Jeffery Reinking (1945-2011) and the author partnered to establish intractable pain clinics in Northern California between 1998 and 2010. He was a most gregarious and lovable man who was a professional member of a number of national and international organizations including the International Association for the Study of Pain, the American Academy of Pain Medicine, The International Association of Pain and Chemical Dependency, and the American Medical Association. Dr. Reinking was recognized as a pioneer in the interdisciplinary approach to the treatment of chronic pain. In his work, he realized that a sub-group of chronic pain patients had constant, intractable pain that required ongoing medical treatment. At the time of his death, he had about two dozen intractable pain patients who had taken high daily dosages of opioids for twenty to thirty years. The author evaluated these patients and found they functioned well mentally and physically. Monor endocrine(hormonal) deficiencies were the only physiologic abnormalities found in Reinking’s patients. The author best remembers Dr. Reinking making this statement, “I can’t explain it, but the intractable pain patients who take a lot of vitamins and supplements just do a lot better.”
*Campbell ND, Olsen JP, Walden L. The Narcotic Farm: the rise and fall of America's first prison for drug addicts. Harry Abrams, New York, NY 2008.
History of the term "Intractable Pain"
The word “intractable” simply means “incurable.” The term was first popularized by British and Irish physicians, who formed “The Intractable Pain Society” in the mid-20th century to enhance diagnosis and treatment of the condition.
The first use of the term to describe its physiologic complications was in 1978 when two Canadian physicians (Glynn and Lloyd) used the term intractable in a paper entitled, “Biochemical Changes Associated with Intractable Pain.” As reported in the British Medical Journal, they found that these patients had elevated carbon dioxide levels due to impairment of breathing that intractable pain may produce. This study was not only the first to use the term intractable, it demonstrated that persons with intractable pain had objective physiologic abnormalities that separated them from the simple chronic pain patient. It was not the first study to demonstrate that severe chronic pain may cause biochemical changes in the body. A Philadelphia neurologist by the name of Shenkin, shortly after a blood test for cortisol was developed, found in 1964 that cortisol levels were pathologically altered in some chronic pain patients.
In the 1990s, some state legislatures began passing intractable pain laws. We assume they adopted the name intractable as a result of the papers written by physicians who labeled some patients intractable. State laws have all stated that intractable pain is “incurable by any known means.” It was well known that intractable pain was often refractory to standard treatments, and opioid medications at non-standard doses were often needed to relieve pain. These laws are intended to permit physicians to prescribe opioids without retribution or discipline by their state medical boards. These laws were helpful for a couple of decades, enabling highly effective, individualized care of persons suffering from IP.
However, these laws have had a tragic outcome. In recent years, states have essentially ignored these laws and continued to prosecute physicians, declining to acknowledge the laws or the intended meaning of the term intractable pain. States have even stated that the intractable pain laws only apply if a physician is disciplined or prosecuted and wishes to challenge in a court of law. We know of no instance where this has occurred.
The term “intractable” has not been embraced by any professional organization. There was a movement to replace the term “intractable” with “persistent,” but it has not found any widespread acceptance either, as it is more ill-defined than the term intractable. It also trivializes those persons with IPS who should be viewed as having a catastrophic illness.
In summary, the term intractable has emerged in that it signifies both an incurable state and implies that a subgroup of severe chronic pain patients exists among the population of chronic pain patients. Neither the term persistent nor the concept of chronic pain as a disease has found general acceptance, and all persons who have a painful condition that lasts over 90 days have continued to be labeled as having “chronic pain.” The major issue and advice we offer here is that science has now provided both the knowledge and diagnostic testing ability to identify chronic pain patients who no longer have “simple” pain and have developed “Intractable Pain.”