Epstein-Barr Virus Emerging As Possible Cause of Chronic Pain

By Dr. Forest Tennant, PNN Columnist 

When most people hear about the Epstein-Barr virus (EBV), they may recall its reputation as the rather harmless "kissing disease" known as mononucleosis.  To the surprise of many, this previously unheralded virus has recently emerged as a cause of some cancers and painful disorders.

It is now clear that EBV must be contained and suppressed in order to relieve the pain and suffering of many persons with chronic pain. This column is an introduction to the critical involvement of EBV with several chronic pain conditions.

The Epstein-Barr virus is named after Drs. Anthony Epstein and Yvonne Barr. In 1964, they discovered the virus after they found it in a cancer common in Africa called Burkitt’s Lymphoma.  Since that time, EBV has been found to cause other cancers including nasopharyngeal, gastric, Hodgkin’s lymphoma, and leukemia.  Some estimate that EBV causes about 200,000 cancers a year.

About three years after Epstein and Barr discovered EBV, it was found to be the cause of infectuous mononucleosis, which is known to trigger autoimmune complications.  Autoimmunity is simply defined as some element in the body that attacks, erodes, and destroys tissue. 

In 1968, this author reported that mononucleosis could cause glomerulonephritis, an autoimmune renal disease.  Over the ensuing decades, EBV has also been associated with other autoimmune disorders, including hepatitis, rheumatoid arthritis, fibromyalgia, systemic lupus, and Sjogren's syndrome.

EPSTEIN-BARR VIRUS

In 2018, a seminal study documented that EBV could cause a number of painful medical conditions by activating specific genes.  Dr. John Harley and colleagues at Cincinnati Children's Hospital Medical Center, with funding from the National Institutes of Health, found that a viral protein called Epstein-Barr nuclear analog 2 (EBNA 2) binds to the deoxyribonucleic acid (DNA) of genes that promote autoimmunity and some chronic pain conditions.

The pain conditions that Harley and his colleagues associated with EBV are multiple sclerosis, rheumatoid arthritis, celiac disease, type 1 diabetes, inflammatory bowel disease, thyroiditis, and juvenile arthritis.  Subsequent studies added Sjogren's syndrome, mixed connective tissue disease, and polymyositis to the list of EBV autoimmune conditions.

The Harley research is compelling.  We urgently need clinical studies of EBV in severe chronic pain patients to help develop new diagnostic, prevention, and treatment measures.  To this end, I've chosen to study the EBV relationship to painful spine and connective tissue diseases, especially adhesive arachnoiditis (AA) and Ehlers-Danlos syndrome (EDS). These conditions are considered intractable pain conditions in clinical pain practice. 

So far, we have collected EBV laboratory test results from over 80 persons with confirmed AA. Every case has demonstrated abnormally high levels of EBV IgG antibodies, which suggests the presence of autoimmunity and the possible invasion of brain and spinal tissue by the virus. 

Every patient with high IgG antibody levels also has herniated discs, and the majority have hypermobile EDS. Prior to developing AA, all had conditions associated with autoimmunity, such as fibromyalgia and small fiber neuropathy. All of them now have intractable pain.

How It Begins

Patients and clinicians concerned about chronic pain need to understand the basics of how EBV causes and aggravates chronic pain conditions. 

EBV is a member of the herpes virus family, which includes the other herpes viruses and cytomegalovirus.  It is a natural, lifelong parasite that usually infects children before the age of two. 

When EBV first enters the body, it is an “active” virus that may cause a cold, sinusitis, bronchitis, or possibly even go unnoticed. Infants and young children often have the “sniffles” and it could be mistaken as a simple cold. Some children who initially become infected with EBV later develop mononucleosis in their teenage or young adult life.  

After the initial infection, EBV settles into one’s lymphocytes and lining of the throat and nasal cavity to remain for life. Under normal physiologic circumstances, it is a latent or dormant parasite that does no harm.

Over 95% of adults will test positive for low levels of IgG antibodies, decades after their initial contact with EBV during childhood. When chronic pain patients are tested, autoimmunity is suspected if IgG antibodies are above normal levels found in the great majority of adults.

Once EBV has settled into lymphocytes or the throat lining and becomes dormant, it is living a harmless, symbiotic, parasitic life with its human host.  It will remain in this state, unless the body undergoes some kind of stress, usually trauma or an infection, that lowers or degrades the body's innate or natural immunologic protection systems. 

At this time, the virus may vacate its dormant or latent state to begin what is called a "lytic" or duplicative state.  The term used to indicate this state is "reactivation," meaning that the virus is again active, and attacking and invading new tissues. 

Once reactivated, EBV may create an autoimmune state by altering genes or by developing what is called an auto-antibody that will attack tissues.  In either case, an autoimmune state has been created that attacks normal tissues to produce inflammation, adhesions, scarring, and pain. 

Lymphocytes infected with reactivated EBV may enter any number of tissues. They may cross the blood brain barrier, enter the spinal cord and brain, and attack tissues such as the cauda equina, arachnoid membrane, intervertebral discs, and glial cells. This is the pathologic process in which EBV reactivation may cause chronic pain.

It is likely that entry and invasion of spinal canal and brain tissues may be responsible for the autoimmune manifestations seen after a stroke, head trauma, or complex regional pain syndrome (CRPS).  EBV may also be a cause of centralized pain that is associated with over-sensitization, hyperalgesia, and intractable pain.  There are reports that such common chronic pain conditions as fibromyalgia, small fiber neuropathy, and some arthropathies are caused by EBV autoimmunity.

This article's major intent is to inform all concerned parties that deal with chronic pain that EBV is not just some virus that causes the "kissing disease." It is a new revelation that compels an understanding and awareness that has the distinct potential to improve the plight of chronic pain patients. 

Laboratories and clinical researchers, including this author, are scurrying to identify more diagnostic, treatment, and preventive measures for EBV-caused autoimmunity. I'm pleased to report that our EBV project has been able to identify some initial testing and treatment measures which appear to be effective and a good start in dealing with EBV autoimmunity.  We will share our findings in future articles.

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. Readers interested in learning more about this research should visit the Tennant Foundation’s website, Arachnoiditis Hope. You can subscribe to its bulletins here.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

Opioid Therapy Is Controversial, But Why?

By Barby Ingle, PNN Columnist

There are many factors that contribute to the controversy surrounding opioids, which have been used for thousands of years for pain relief.

Mainstream media often say that opioid medication is harmful and increase the risk of addiction, overdose and death. Many media outlets do not distinguish between FDA approved medications and street drugs, or show the life-giving side of opioid medication.

That is the root cause of the controversy. If people don't understand or are misinformed, they go with what they hear -- right or wrong.

Let’s explore these issues and, hopefully, set the record straight.

Rx Opioid Side Effects

All medications have side effects, including opioids. At least 50% of patients in clinical trials experience a side effect from opioid therapy, such as nausea, vomiting, constipation, dizziness, dry mouth or sedation. These side effects vary and can decrease or increase with long-term use.

Most side effects of opioids improve shortly after therapy begins or following a dose increase. However, itching and constipation can persist throughout treatment. Most of the chronic pain patients I have met on my journey are okay with these side effects and wish to continue with treatment. For others, opioid therapy is discontinued when the side effects are too severe.

A variety of respiratory issues can be caused by opioids, including inadequate breathing, erratic breathing, and impairment of the upper airways. That can lead to respiratory depression, a precursor to an overdose. Patients in acute pain management who are new to opioids are most at risk of respiratory depression because they have not developed tolerance to opioids.

To be clear, an overdose from prescription opioids is relatively rare. A recent study found the risk of a fatal overdose at 90 morphine milligram equivalents (MME) – a fairly high daily dose – is only 0.26%. The risk is even lower at 50 MME – just 0.16%.

Opioids have more respiratory effects during sleep. Several fatalities have been reported in patients with obstructive sleep apnea, who may be contraindicated to opioid therapy. Patients with sleep apnea who take other central respiratory depressants, such as benzodiazepines, should be cautious about this. If opioids are prescribed to patients with sleep apnea, a nocturnal respiratory assessment will be needed.

Patients may absorb more opioids from transdermal opioid formulations if they have a fever or other illnesses. This is also true if they are exposed to heat, such as a sauna.

Is Pain Inevitable?

The Japanese author Haruki Murakami once wrote, "Pain is inevitable. Suffering is optional." Murakami was writing about running a marathon, but it’s an apt description for someone with chronic pain. Does their suffering have to be inevitable?

I didn't understand that concept as a collegiate coach or as an athlete until I developed chronic intractable pain and needed treatment. It is difficult to understand chronic pain or intractable pain if you haven't lived with them.

So that we are all on the same page, chronic pain is defined as pain lasting over three months. Intractable pain is complex and can last a lifetime, causing immense suffering. Acute pain is pain that lasts for less than three months.

Acute pain is usually caused by an injury, trauma or medical condition. Left untreated, acute pain can progress to the chronic stage, causing long-term disability, depression, and impaired quality of life. Therefore, it is essential to identify and treat pain as soon as possible, preferably in the acute stage.

Different approaches, including medication, physical therapy, and lifestyle changes, can be used to manage pain. Finding the right approach for each patient is crucial, as something that worked for one patient may not work for another. It is essential to consider all options before selecting the most appropriate treatment.  

Barby Ingle is a reality TV personality living with multiple rare and chronic diseases. She is a chronic pain educator, patient advocate, motivational speaker, and the founder and former President of the International Pain Foundation. You can follow Barby at www.barbyingle.com. 

How to Recognize and Treat Intractable Pain

By Dr. Forest Tennant, PNN Columnist

The realization that a subgroup of chronic pain patients has intractable pain is finally spreading. Over half a dozen states now have laws protecting intractable pain (IP) patients and Wikipedia refers to IP as a disease that causes “a severe, constant, relentless, and debilitating pain.”

A major impediment to treatment of IP is simply that it is not commonly recognized by either patient or practitioner. Basically, the concept that pain alone can cause serious medical complications is not yet appreciated. This fact is evidenced in product advertising and lay person media articles about “chronic pain.” A close analysis implies that everyone has simple chronic pain and needs a “one size fits all” treatment.

The fact is that the IP subgroup of patients isn’t recognized by even the most sophisticated and prestigious medical institutions. For example, I hear almost daily about a person with IP who has severe hypertension, tachycardia, or even angina without any recognition that IP is the culprit.

Other examples are persons with IP who have hormonal deficiencies. Medical practitioners are treating their patients for such hormonal complications as osteoporosis, impotence, and depression, with no recognition that IP is the cause. Regrettably, some persons have had their pituitary or adrenal removed for a “tumor” when in reality the gland was over functioning and enlarged due to IP.

About half of the persons who develop IP have a genetic or inherited disorder. The most common high risk genetic conditions are Ehlers-Danlos Syndrome (EDS), ankylosing spondylitis, and scoliosis.  Other genetic, but less common, risk disorders include Marfan Syndrome, porphyria, and autoimmune diseases such as rheumatoid arthritis and ulcerative colitis. 

How IP Starts 

Thanks to research and studies in recent years, there is now an understanding of the pathologic sequences that lead to IP.  Basically, IP is the end product of multiple events and conditions that may affect a person.   

IP always has a starting or painful initiating event which is either traumatic or inflammatory. Typically, the initiating event takes place several months or years before IP symptoms develop. 

The most common traumatic events are falls, altercations or surgery. Trauma may be to the head, spinal cord, or a nerve in the arm or leg.  The most common initiating inflammatory disorders are fibromyalgia, severe respiratory infection or arthritis. 

The initiating event doesn’t usually cease but “smolders on” with pain that comes and goes.  A diagnosis of chronic pain is likely assigned, and a wide variety of medications and other measures are attempted.   

Interestingly, an initiating inflammatory event such as arthritis or fibromyalgia may seemingly spread. The person may develop additional inflammatory disorders such as thyroiditis, carpal tunnel syndrome, migraine, and irritable bowel. 

Trauma may be severe or minor and the sequelae quite variable. Neuropathies or intervertebral disc degeneration and herniation are the most common traumatic complications that lead to IP.  Pain after the initiating event is usually not constant, but at some point becomes constant. 

This constancy is associated with inflammation that develops in the brain and/or spinal cord of the central nervous system (CNS). Cells called glia or microglia promote CNS inflammation, which can damage the neurotransmitter-receptor systems that control pain.   

Exactly how injuries and inflammatory disorder activate glial cells to produce CNS is unclear. The two most discussed mechanisms are excess electromagnetic energy generated in the injury and inflammatory sites, and autoimmunity or viral invasion of CNS tissue.  The Epstein Barr virus is the most likely virus.

The first chapters of my new book, “Handbook for Intractable Pain,” are dedicated to how to recognize IP symptoms. The second section is a step-by-step treatment program of self-help.

IP doesn’t have to thrust a person into misery and a short life if a three-component protocol is followed:

1. Suppression of inflammation and autoimmunity

2. Restoration of damaged tissues

3. Pain control

To carry out this protocol, one has to become knowledgeable about IP and build, over time, an effective therapeutic program.

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain. To Tennant Foundation has launched a new website, IntractablePain.org, where you can learn more about the conditions that cause intractable pain and their many complications.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

We Must Overcome Stigma Against Buprenorphine for Pain

By Dr. Stefan Franzen

For years I had a negative impression of buprenorphine as a pain medication, both from personal descriptions I had heard by pain patients and from the scientific and medical literature.

I have since learned that buprenorphine can be effective pain reliever. At a high dose, the efficacy is similar to that of high-dose morphine or oxycodone, which were once commonly used to treat chronic or intractable pain.

Today, high doses of any opioid are shunned by most doctors because they are subject to increased scrutiny by state medical boards or even investigation by the Drug Enforcement Administration. The medical and moral justification of alleviating patient suffering appears to be irrelevant to public health authorities, even when they profess to favor a humane policy to treat pain.  

We need a more rational discussion about opioids. Buprenorphine is an opioid that, when used alone, can play a role in pain treatment. Buprenorphine was developed in the United Kingdom in the 1960s and has been used in many countries to treat pain since the 1980s.

We must distinguish pure buprenorphine from Suboxone, which is a combination of buprenorphine and naloxone. Suboxone is given to people with opioid use disorder to help prevent abuse. If a tablet is crushed, extracted or injected by a drug abuser, the naloxone will block the effects of buprenorphine. However, if taken as directed under the tongue, the naloxone has much lower bioavailability.

A pain patient does not necessarily need naloxone and, depending on individual differences in body chemistry, the naloxone may even have negative effects. There is no reason to prescribe Suboxone for pain. It’s use as a pain medication is highly inappropriate, but may be the result of doctor’s fear of DEA action.

Pure buprenorphine is a different matter.

The CDC’s 2016 opioid guideline recommended that daily opioid doses not exceed 90 morphine milligram equivalents (MME).  Although voluntary, the guideline was seized upon by other federal agencies and state legislatures to justify draconian new laws and regulations that limited opioid doses to 90 MME or less.

No such limits have been set for buprenorphine. However, few doctors in the U.S. prescribe buprenorphine for pain, despite recent studies demonstrating its efficacy and international recognition that it is an effective analgesic.

For historical reasons, American doctors do not know much about buprenorphine as a pain medication. Moreover, many fear prescribing any opioid in today’s regulatory climate. Patients know that buprenorphine has been used to treat addiction and therefore are suspicious of it as a pain treatment. They are also justifiably concerned about being stigmatized as a drug abuser if they are prescribed Suboxone.

U.S. Opioid Policy Lacks Common Sense

In short, the stigma surrounding buprenorphine is a significant factor preventing development of a rational opioid policy in the U.S.

Many patients with experience taking morphine, oxycodone, hydrocodone and other opioids say they are safe and non-addictive. Research shows that is true for a great many pain patients. However, a small fraction of the population is susceptible to opioid abuse and addiction. This is a classic ethics problem.

Should we let 99% of patients suffer because 1% might harm themselves? How do other societies manage this problem? We know what doesn’t work. The “War on Drugs” has been an unmitigated disaster for everyone: drug abusers, doctors, pain patients and their loved ones. Our drug overdose rate is 15 times higher than that the of European Union.

Worse still, our medical system and corporate regulation appear to lack common sense guardrails needed to prevent the diversion of prescription opioids -- even after massive publicity, sensational books, documentaries, and popular miniseries on the opioid crisis.

In case anyone had any doubt, the book “American Cartel” shows that diversion was mainly practiced by large opioid distributors and a few manufacturers, who flooded vulnerable communities with prescription opioids. Theft and deception of doctors by drug abusers also contributed to diversion. Each of these could be controlled in a sensible way, without forbidding people in pain from receiving medication. Yet, at present it appears there is no political will in the U.S. to even treat pain, regardless of the suffering of millions.

Instead, the politicians and media blame opioid prescribing, which implicitly blames doctors and patients. Perhaps as a response to this seemingly hopeless situation, a growing number of medical researchers have begun testing pure buprenorphine for the treatment of pain.

After seeing the effectiveness of buprenorphine, which I discuss in my new book, “Z’s Odyssey,” I became convinced that it is a viable treatment for even severe, intractable pain. This should be a choice, but the problem today is that many patients do not have a choice.

Pure buprenorphine for pain was not available in the United States until 2010, when the low-dose Butrans skin patch became available.

In 2015, a buccal formulation designed for absorption through the cheek became available. Belbuca film is quite convenient and comes in a moderate dose.

For intractable pain, a sublingual formulation of buprenorphine known as Subutex can be prescribed off label for pain. Subutex is also used to treat opioid addiction, but does not contain naloxone.

A Subutex tablet placed under the tongue takes about 20 minutes to be completely absorbed. Because buprenorphine binds to the pain receptors more tightly than any other opioid, the dose in milligrams required for full effect is much lower than similar strength morphine. Many medical researchers have concluded that buprenorphine is an excellent analgesic, with low risk for addiction or overdose. If taken as directed, the risk of respiratory depression from buprenorphine is the lowest of any opioid.

For pain relief, U.S. doctors must prescribe Subutex off-label, which means that they are prescribing for a condition that is not FDA approved.  Subutex is approved for pain in Great Britain and most of Europe. The UK’s National Health Service recommends Subutex and other formulations of buprenorphine for patients “when weaker opioids for pain stop working.”

Of course, buprenorphine is not beneficial for every patient. And there is an issue of dental decay that requires careful monitoring and appropriate procedures. But for people in the most severe pain, who lack any other option because of the opioid prohibition mindset, buprenorphine may offer relief.

Finding a doctor willing to prescribe Subutex off label could be difficult. For severe or intractable pain that requires a high dose, a patient most likely needs to find a psychiatric or addiction treatment doctor licensed to prescribe buprenorphine in formulations such as Subutex that are pure buprenorphine.

Since 2000, the U.S. Congress has passed three laws that make buprenorphine more accessible to people with opioid use disorder.  If Congress can aggressively lower the barriers to prescribing high-dose buprenorphine for addiction treatment, then why shouldn’t pain patients have access to medication that has the same dose of the active agent?

There is an education gap that prevents doctors and society at large from effectively managing this situation. The medical literature is heavily weighted toward studies of buprenorphine for addiction, with almost 97% of studies on opioid use disorder and less than 3% on pain.  Pain patients also fear the stigma associated with buprenorphine as an addiction treatment, rather than an analgesic.

There is no objective reason for this. At the very least, buprenorphine should be an option for those forgotten patients who still live in pain. By overcoming the stigma of buprenorphine, doctors could treat patients with dignity by prescribing a safer and more effective medication. 

Stefan Franzen, PhD, is a Professor of Chemistry at North Carolina State University. Franzen is the author of “Patient Z” – a book that looks at pain, addiction and the opioid crisis through the eyes of a patient who can’t find good pain care. He recently published a sequel to Z’s story, called “Z’s Odyssey.”

Understanding the Difference Between Chronic Pain and Intractable Pain

By Dr. Forest Tennant, PNN Columnist  

The difference between simple chronic pain and intractable pain (IP) is what is known as pathologic sympathetic overdrive. This major medical complication is characterized by excessive electrical activity in the body's sympathetic nervous system. Excess electricity causes hyperarousal and pathologic overactivity of the sympathetic nervous system, which controls the body’s stress response. A comprehensive grasp of this complication is crucial for effective treatment.

Pathologic complication is the root cause of the disability, profound suffering and shortened lifespan often caused by intractable pain. Even though I recognized and published the difference between chronic and intractable pain in the Western Journal of Medicine over 20 years ago, it is still poorly understood in the mainstream medical practices of today. This contributes greatly to the undertreatment and mistreatment of IP patients.

The severe, constant and disabling pain of IP causes anatomical defects in the brain, which leads the cells in the brain to generate excess electricity. This is how pathologic sympathetic overdrive (PSO) starts. The brain must get rid of the excess electricity to prevent damage from the “burning” of brain tissue.

The brain rids itself of excess electricity by sending it into the sympathetic nervous system. This system is comprised of nerves that connect the brain to the heart, blood vessels, skin, lung and gastrointestinal system. The best-known neural connection in the network that connects the brain to bodily organs is the vagus nerve, but there are less known nerve connections in and along the spinal cord.

The “overdrive” of excess electricity produces a typical set of easily recognized symptoms and physical signs. These include an elevated pulse rate (tachycardia), high blood pressure, cold extremities (sometimes exhibiting a bluish hue), goosebumps, dilated pupils, and hyperactive reflexes. Another common symptom is temperature spikes and flushing, often followed by chills.

Amazingly, while the nation persistently clamors about the importance of controlling blood pressure, making Americans very aware that hypertension leads to serious medical conditions and is one of the leading causes of death in the U.S., I cannot identify a single lay magazine or medical journal that even refers to the undeniable correlation between severe, unmanaged pain and high blood pressure.  Strangely, there is also a conspicuous absence of discussions even in medical publications about the necessity of adequate pain management to reduce blood pressure.

Complications Caused by Intractable Pain

PSO interferes with normal respiratory function. The lungs may not expand and bring in the normal level of oxygen, and carbon dioxide may elevate in the blood. Inadequate oxygenation may lead to lethargy, fatigue, poor motivation, muscle weakness and mental impairment.

An IP patient’s ability to sleep, and especially achieving adequate REM sleep, is greatly reduced by PSO.  The hazards of inadequate sleep are well-known: fatigue, depression, amotivation, poor mental activity, and hormone imbalances. A tragic misunderstanding is the belief that somehow a lack of sleep is better than taking a bedtime sedative. This notion lacks any scientific merit.

There are lesser known but other serious and debilitating sequalae of PSO. The gastrointestinal system becomes so impaired by PSO to the point that loss of appetite, malabsorption (nutrients do not assimilate) and malnutrition is present in essentially all IP patients. The disturbed nutritional metabolic deficits can lead to either significant weight gain or loss. Constipation and diarrhea will often alternate, while stomach pain and bloating are routine. Patients are often misdiagnosed as having irritable bowel syndrome (IBS), with treatment that gives no consideration that bowel symptoms will persist without control of the underlying IP.

PSO has a significant impact on the endocrine system, similar to the body's "fight or flight" response during moments of stress. With IP the stress is constant. This physiological response involves an increase in adrenaline and cortisone levels in the bloodstream. Normally, this response to stress is temporary, allowing the adrenal and pituitary glands to recover and remain intact. But with the constant pain and electrical overdrive of IP, the glands hypertrophy (enlarge abnormally) trying to keep up their hormonal output to protect the body.

Unfortunately, the glands will often deplete. IP patients have died due to adrenal failure as the glands could not produce enough cortisone and adrenaline to maintain life. PSO tends to especially cause the pituitary gland to enlarge. Some uninformed surgeons have “removed the pituitary tumor” without understanding the root cause of the enlargement, or the imperative need to manage pain.

If PSO goes on long enough, and the pituitary and adrenal glands exhaust or wear out, testosterone and estradiol will deplete. While most people are aware of the impact of such depletion on libido and menstrual functions, what many medical practitioners miss is the critical role these hormones play in tissue healing, pain reduction, and various mental functions.

Since PSO raises cortisone for as long as one has IP, calcium is extracted from bones and teeth. Osteoporosis may develop and teeth may deteriorate. Sudden loss of a tooth is common in IP as is chronic dental cavities.

PSO in an adult IP patient will often cause some level of adult attention deficit disorder (ADD/ADHD), which is the exact clinical syndrome that occurs in a child with hyperactivity or attention deficit disorder. Furthermore, when the IP patient develops the same “attention deficits,” they will need the same medications that a child does to normalize attention span, carry out the 3R’s (“reading, riting, rithmetic”), and activities of daily living.

The mental aberrations caused by IP, unless treated with today’s hyperactivity medications (Ritalin, Adderall), can be so debilitating that the IP patient can become a lonely, despondent invalid, who becomes expensive to care for and totally dependent on family and society. The medical profession’s rejection or dismissal of ADD/ADHD in IP patients can only be classified as blatant professional oversight.

Diagnosing Intractable Pain

It is essential to point out that a medical practitioner who understands PSO can distinguish an IP patient from a simple chronic pain patient with a 5-to-10-minute physical examination. For starters, the IP patient with PSO will show some abnormality of pulse-rate, blood pressure, temperature or breathing rate. Some reflexes will be hyperactive, and the pupil may be dilated.  Hands and feet will be cold to touch and may show a blue discoloration. Teeth will be missing and/or show a lot of decay. Mental activity and speech may be slow and deliberate. Movement also may be slow.

These physical signs correlated with the history and symptoms provided by the patient and family will easily and quickly nail down the presence of IP and PSO, without the need for blood tests or brain scans.

This essay is a call for all parties concerned to fully understand the difference between chronic pain and intractable pain with PSO. Every IP patient, family and medical practitioner must fully understand that PSO will cause dire complications. IP patients and their families need to recognize them and record their PSO manifestations and present them to their medical practitioners.

Sadly, this author cannot identify a single education effort by a recognized medical publication, organization or academic institution that has or is currently trying to educate on the obvious and blatant clinical manifestations of the sympathetic pathological complications of IP. Like most things in medical science and practice today, the demand and education must “start at the bottom and work up.”

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain. To help patients and clinicians better understand intractable pain, the Tennant Foundation has launched a new website, IntractablePain.Org, where you can learn more about the conditions that cause intractable pain and their many complications.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

What Is End-of-Life Care?

By Dr. Forest Tennant and Kristen Ogden

The Medical Board of California’s new Guidelines for Prescribing Controlled Substances for Pain are futuristic and practical.  They recognize that persons who need intractable pain or “end-of-life” care may often require a non-standard medical program, so the board made these two conditions exempt from any limitations on dosage or treatment.

In our recent column on the guidelines, we clarified the meaning of intractable pain and suggested criteria for identification of the intractable pain patient who requires non-standard drugs and dosages. This column does the same for “end-of-life” care. 

The California guidelines define end-of-life care as “for persons with a terminal illness or at risk of dying in the near future whether in hospice care, hospitals, long-term care or at home.”  Note that this definition does not include palliative care, whose definition is frankly now in limbo, because medical textbooks define it as “symptomatic rather than curative care.” Third party payers only recognize palliative care as being in the last few months of life.

How does one identify a person who needs “end-of-life” care?  California actually has a law which helps identify the person who needs end-of-life care.  Such a person “is suffering from an incurable and irreversible illness that will bring about death within one year if the illness takes its normal course and the treatment is for pain control and/or symptom management rather than to cure the illness.” 

In effect, this definition includes intractable pain patients who are not expected to live more than a year without treatment.  Severe intractable pain, regardless of cause, if left untreated will result in malnutrition, immune deficiency, cardiac or adrenal failure, and a shorter life. 

To our knowledge there are no formal criteria published for clinicians to determine when there exists high risk of death within a year.  Here are criteria used and suggested by us: 

1. Patient has a known disease that may shorten life, such as cancer, adhesive arachnoiditis, head trauma, and Ehlers-Danlos syndromes.

2. Pain is constant and interferes with activities of daily living as reported by a close family member.  Examples are inability to eat, toileting, mobility, hygiene, and dressing.

3. Bed bound and immobile for many hours of each day.

4. Malnutrition, evidence of tissue loss, poor skin turgor (rigidity), and/or weight loss.

5. Family reports inability to normally read, answer questions, or socially respond.

6. Some alterations in normal physiologic functions such as blood pressure, pulse, and hormone levels.

We encourage clinicians to use our criteria for “end-of-life” care or develop some specific alternative criteria.  Too many seriously ill intractable pain patients have been denied care until it was too late.  An “end-of-life” case may begin at any age, be it 14, 40 or 80 years old. 

Many, if not most “end-of-life” patients meet terminus within a year. But some persons turn things around with adequate intractable pain care and live much longer.

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain. The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

Kristen Ogden is a patient advocate from Virginia. Kristen and her husband Louis travel regularly to California for his intractable pain treatment and prescriptions, which are not available in their home state.

The Way Forward: California’s New Opioid Guidelines

By Dr. Forest Tennant and Kristen Ogden

The Medical Board of California recently published new guidelines for prescribing opioids and other controlled substances for pain, which emphasize “individualized care” that is customized for each patient. 

The guidelines are a remarkable, positive and practical way forward in pain care. All persons concerned about chronic pain treatment with opioids, benzodiazepines and other controlled drugs need to know the basic concepts embedded in them.    

As the medical board was updating its guidelines, we had great concern that they would bury California’s Pain Patient's Bill of Rights and Intractable Pain Treatment Act. When these laws were passed in the 1990’s, they were a godsend to patients with chronic intractable pain, who were given the right to “request or reject the use of any or all modalities in order to relieve his or her pain.”

That means patients, with the support of their doctors, could get opiate medication without first having to submit to surgery, medical devices and other forms of pain treatment.  

To our great pleasure, the medical board’s new guidelines recognize, define and support these worthy laws.  Importantly, the guidelines also state that they are “not in any way intended to limit treatment” of patients in hospice or palliative care. And they allow for doctors to prescribe high dose opioids, provided they keep good medical records that document a need for them.

Defining Intractable Pain

The California guidelines provide a classic definition of intractable pain as “a state in which the cause cannot be removed or otherwise treated and no relief or cure has been found after reasonable efforts.” 

The problem with this definition is that intractable pain may be mild or intermittent and not curable, but may still be treated with non-opioid modalities. To require and receive treatment with opioids and other controlled drugs, one really needs a specific causative diagnosis of the unremitting “high impact” pain that produces physiologic complications such as hypertension, tachycardia, and endocrine deficiencies. 

Put another way, is intractable pain an incurable but treatable problem? Or is it constant and incurable with potentially life-threatening complications? 

Physicians, as a group, are often mystified, confused and unaware of how to determine which patients have an incurable, but readily treatable problem, and which patients have the constant and incurable pain that causes complications and require opioid therapy.

Physicians need help to make sound, defensible treatment decisions in the face of this quandary.  Some patients with complex intractable pain are greatly impacted and require non-standard treatment, which may include high-dose opioids, benzodiazepines and stimulant drugs. 

Here are the recommended criteria to identify such patients and support non-standard treatment plans.

1. A specific medical cause of intractable pain has been identified.

2. Constant pain has impacted some physiological and/or mental functions such as sleep, eating, hygiene, reading, concentration, and mobility.

3. Trials of standard medications and dosages with such agents as anti-depressants, muscle relaxants, anti-inflammatories, stimulants, anti-seizure medications, and low-dose opioids have not controlled pain or normalized functions.

4. There is objective physical evidence of the causative disease or complications of the pain, such as hypertension, tachycardia, neurologic deficits, or anatomic structural abnormalities.

5. There is an objective, diagnostic test result that documents an abnormality of the cause of pain or its complications, such as a magnetic resonance imaging (MRI), hormone deficiency, elevated autoimmune or inflammatory marker, or an abnormal electrodiagnostic test.

It is the lack of adequate treatment of complex intractable pain that is really the crux of the suffering and deaths that have emerged due to overzealous and misinformed opioid regulations and guidelines.  These legitimate, complex patients comprise about 3 to 5% of chronic pain patients.

The California medical board’s new guidelines provide clinicians the opportunity to implement individualized and effective treatments for these unfortunate and deserving intractable pain patients. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain. Dr. Tennant was the lead physician in crafting California’s Intractable Pain Law and Pain Patient Bill of Rights, and worked with the legislature to get them passed. 

Kristen Ogden is a patient advocate from Virginia. Kristen and her husband Louis travel regularly to California for his intractable pain treatment and prescriptions, which are not available in their home state. Kristen testified during public hearings on the California guidelines and closely followed their development. 

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

Army Veteran Is Latest Casualty of DEA’s War on Drugs

By Pat Anson, PNN Editor

Becky Snyder and her husband Vance were soldiers when they first met in 1979 at Fort Lewis, Washington. Becky was a legal clerk for the Army, while Vance was a combat medic who later became an Army-trained physician assistant and chief warrant officer. They soon married and had a son.

After years spent defending their country, Vance and Becky could not have imagined they’d windup becoming unintended casualties of the DEA’s failed War on Drugs. Vance lost the love of his life when Becky died last month at the age of 70, after a lifetime of suffering from chronic pain.

“She had scoliosis her whole life, probably congenital. And that made it hard for her to do sit ups in the in the military and probably injured her spine trying to do that,” said Vance. “She could walk with difficulty. Usually when we went out, we used a wheelchair.”

Becky’s back pain progressively worsened and she became bedridden after developing intractable pain from two very serious complications: Complex Regional Pain Syndrome (CRPS) and arachnoiditis, a chronic inflammation of spinal nerves.

Both conditions are incurable and cause severe pain, but Becky found relief under the care of two Los Angeles-area doctors, Forest Tennant and David Bockoff. 

BECKY SNYDER AND SON

The careers of both physicians effectively ended after their offices were raided by DEA agents, Dr. Tennant in 2017 and Dr. Bockoff in 2022. They were targeted by the DEA for giving patients like Becky with complex medical conditions high doses of opioid pain medication — which, in the eyes of the DEA, has no legitimate medical use.

There is no evidence that any of Tennant’s patients were harmed or overdosed while under his care, but he retired in 2018 rather than face a costly legal battle with the DEA and Department of Justice.

Becky and other Tennant patients became “opioid refugees,” scouring the country for doctors because no one was willing to treat them locally. Several eventually found their way to Bockoff, with some traveling thousands of miles from out-of-state to see him and get their prescriptions filled in California. That made Bockoff a target for the DEA.

Last November, the DEA suspended Bockoff’s license to prescribe opioids and other controlled substances, even though he practiced medicine for over 50 years in California with no record of any disciplinary action or complaints filed with the state medical board. The DEA claimed five of Bockoff’s patients were in “imminent danger,” but then waited a year to suspend him.  

Patient Deaths

While Bockoff appeals his suspension, at least three of his former patients have died, including one who committed suicide with his wife and another who died after buying opioid medication in Mexico. Becky Snyder is the most recent death.        

“The last six years have been very difficult, because we couldn’t get the amount of medicine that Dr. Tennant gave. Dr. Bockoff, I mean to his credit he did the best he could, but he couldn’t give the amount that Forest Tennant was willing to give,” said Vance.

“But if there hadn’t been Dr. Bockoff, I think she would have died even sooner.”

Becky didn’t die from withdrawal, but from pancreatic cancer. She was diagnosed earlier this summer after complaining of stomach pain, and the cancer quickly metastasized. Becky didn’t drink, and Vance is convinced that poorly treated pain contributed to her death.

BECKY SNYDER

“I was in Army medicine. Clinically and diagnostically, pain can be an important indicator of what’s wrong with a patient. You have to take the suffering seriously,” Vance told PNN. “I believe pain kills people all the time because it just wears the person out. It leads to all kinds of conditions, whether it’s endocrine, whether it’s cancer, whether it’s depression and suicide. There’s all kind of things that pain causes.”

“Cancer follows intractable pain like night follows day,” says Tennant, who believe Becky’s death was preventable. “Because if you can’t get the pain relieved, you disturb your hormonal systems and your immune system. I can’t tell you how common cancer is in these people who can’t get care. It’s just one of the complications.

“I’m sure if I was still in practice or Dr. Bockoff was, she’d still be alive.“

Vance Snyder says intractable pain took a toll on Becky’s physical and mental health, and she aged considerably in her final years. He believes high dose opioids is what kept her alive.

“For the worst, worst cases of intractable pain, opioids have to be part of the package. The idea that nerve blocks, epidurals, aromatherapy, cognitive behavioral therapy and all those things are going to make a big difference with the worst kind of pain is ridiculous,” he said.

Snyder has joined with several other Bockoff patients in a lawsuit asking the U.S. Court of Appeals to give them legal standing as interested parties in the Bockoff case. 

In an open letter, Snyder urged the court to find a “proper balance” between appropriate pain care and the needs of law enforcement.

“Severe intractable pain does not exist in isolation, but is connected to every other aspect of the patient’s overall health,” he wrote. “Becky is gone now, but there are many thousands of agonized patients who are desperate and on the verge of suicide. Please think about them when you make your decisions.”     

Polypeptides: A Promising Treatment for Intractable Pain

By Dr. Forest Tennant, PNN Columnist

We have long noted that persons with adhesive arachnoiditis (AA) and other causes of intractable pain who follow a high protein diet and take amino acid supplements usually have better treatment outcomes. They need fewer opioids, function better, and have a good quality of life.

Protein is composed of about two dozen separate building blocks called amino acids. Once ingested, they chemically join together and cause specific effects in the body. When two or more amino acids combine and partner, they are called polypeptides. Two polypeptides that relieve pain and heal damaged tissue are KPV (lysine-proline-valine) and Body Protection Compound or BPC-157.

KPV is useful primarily for pain relief and to reduce inflammation in the brain and spinal canal. It activates the neurotransmitters endorphin and melanocortin, which are stored in the hypothalamus. 

BPC-157 is a chain of 15 amino acids. Its primary function is to regenerate and heal tissue, including neural tissues, receptors, arachnoid membrane, cartilage and intervertebral discs. We believe it also helps heal spinal fluid leaks. BPC has a great effect on the stomach and intestine. 

Because polypeptides (PP’s) are fundamentally a conglomeration of food particles, when swallowed they are digested in the stomach and lose much of their effectiveness. That is why KPV and BPC-157, like insulin, are often taken by subcutaneous injection. Both PP’s are also available in non-injection formulations. KPV comes in an oral or nasal spray, while BPC-157 is available as sublingual tablet taken under the tongue or as a spray. 

A list of several companies that supply PP’s online is available in this bulletin.  

Who Should Take Polypeptides  

We have long-recommended a three-component medical protocol for AA and other causes of intractable pain to (1) suppress inflammation and autoimmunity, (2) regenerate tissue and (3) relieve pain. Our starting protocol for AA is now changed and anchored with KPV and BPC-157.  

To start, we recommend daily use of a polypeptide for a week. After a week, use it 3 to 5 days a week. Some persons with AA like to use KPV daily as it greatly reduces pain. Others can become tolerant to polypeptides, so skipping some days will keep the polypeptide active and effective.  

All persons with AA and/or intractable pain should, in our opinion, try the two PP’s provided here to enhance pain relief, promote tissue regeneration and healing, and reduce the use of potent medications, including corticosteroids, ketorolac, benzodiazepines, and opioids.  We also believe PP’s can reduce the use of risky surgery and invasive procedures.  

Several other polypeptides are being studied, and the Tennant Foundation will keep you apprised of new discoveries and developments. We consider polypeptides a major advance in the treatment of AA and other intractable pain conditions. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. This column is adapted from bulletins recently issued by the Tennant Foundations’s Arachnoiditis Research and Education Project. Readers interested in subscribing to the bulletins should click here.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.  

Deaths of Intractable Pain Patients Often Mistaken as Overdoses

By Dr. Forest Tennant, PNN Columnist

Unexpected and sudden death commonly occur in persons who have poorly controlled pain caused by Intractable Pain Syndrome (IPS). Many persons with IPS who have died unexpectedly have been falsely accused of an “overdose” because drugs were found in their body fluids at autopsy. In reality, the cause was almost always cardiac arrest, hypoglycemia or adrenal failure.

Cardiac Arrest

Pain flares during cardiac arrest may cause the adrenal glands to pump out so much adrenalin that their blood pressure and pulse rate jump up dramatically. This causes blood vessels, including the coronary arteries and those in the brain, to constrict and shut off blood flow. The result may be a heart attack, stroke or arrhythmia.

Chronic, recurrent coronary constriction may cause heart pain called “angina.” A person with IPS who has their medications, usually opioids or benzodiazepines, reduced too rapidly is very prone to cardiac arrhythmia and cardiac arrest.

Hypoglycemia

Insulin is normally made and secreted by the pancreas to lower blood sugar in order to digest food and stabilize metabolism. In times of pain, cortisol and blood sugar are raised. When this occurs, insulin is pumped out by the pancreas to heal injured or damaged tissues. Too much insulin caused by a pain flare can force blood sugar to drop to such a low level – a condition known as hypoglycemia -- that death may occur.

The long-term effect of constant pain on the pancreas is an insulin deficiency, so high blood sugar levels (diabetes) are regularly found in persons with IPS.

Adrenal Failure

Uncontrolled constant pain may exhaust the adrenal glands to a point that the hormone cortisol drops too low, causing Addison’s disease or adrenal insufficiency. Symptoms such as darkened skin, abdominal pain and weakness usually appear slowly, but if there’s rapid onset of symptoms it could lead to adrenal failure and death.

Addison’s Disease is named after Dr. Thomas Addison, who described 11 cases of adrenal failure in 1855. About half his cases had histories of severe pain. Persons who die of adrenal failure often do so in their sleep.

Many persons with IPS have unexpectedly and suddenly died and have been falsely accused of drug overdose. To prevent sudden death, persons with IPS must be in a pain treatment program that is balanced and doesn’t rely just on just one or two medications.

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. This column is adapted from a bulletin recently issued by the Intractable Pain Syndrome Research and Education Project.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

How Intractable Pain Causes Brain Tissue Loss

By Dr. Forest Tennant, PNN Columnist

The brain not only controls pain but the endocrine, cardiovascular, metabolic, respiratory and gastrointestinal systems. Any or all of these biologic systems may malfunction if there is brain tissue loss.

Beginning in 2004, brain scan studies began to document that brain tissue loss can be caused by intractable pain. Today, almost 20 years later, this important fact appears to be either unknown or a mystery to both the public and medical professionals.

Basic science researchers have unraveled the complex process of how and why this pathological phenomenon may occur. A good understanding of how this pathology develops is critical to properly care for and treat persons who develop intractable pain whether due to a disease or an injury.

What Causes Tissue Loss?

Tissue loss anywhere in the body is caused by inflammation, autoimmunity, or loss of blood supply due to trauma or disease. The brain scan studies done since 2004 that documented brain tissue loss were not done in persons who had a stroke or head trauma, but in pain patients experiencing inflammation and autoimmunity (i.e., collagen deterioration). It turns out that both biologic mechanisms may operate to cause brain tissue loss in intractable pain patients.

In the pursuit of understanding brain tissue loss and its accompanying malfunctions, it has been discovered that the brain and spinal cord (central nervous system or CNS) contain cells called microglia. They are closely akin to the immune protective cells in the blood stream which are called a “lymphocytes.”

The microglia in the CNS lay dormant until a harmful infection, toxin or bioelectric magnetic signal enters its domain, at which time it activates to capture and encapsulate the danger or produce inflammation to destroy the offender.

If the microglia are overwhelmed by some danger, such as a painful disease that isn’t cured, it produces excess inflammation that destroys some brain tissue which can be seen on special brain scans. Some viruses such as Epstein Barr may hibernate in microglia cells and create an autoimmune response, which magnifies inflammation and brain tissue loss.

Intractable pain diseases such as adhesive arachnoiditis (AA), reflex sympathetic dystrophy (CRPS/RSD), and genetic connective tissue diseases such as Ehlers-Danlos syndrome may incessantly produce toxic tissue particles and/or bioelectromagnetic signals that perpetuate microglial inflammation, tissue loss and CNS malfunctions.

This is the reason why proper pain management must have two targets: the pain generator and CNS inflammation.

How To Know You Have Lost Brain Tissue

If your pain is constant and never totally goes away, it means you have lost some brain tissue and neurotransmitters that normally shut off pain. If you have episodes of sweating, heat or anxiety, you probably have inflammation that is flaring. Naturally, if you feel you have lost some reading, calculating or memory capacity, it possibly means you have lost some brain tissue. MRI’s may also show some fibrous scars.

Fortunately, studies show that if a painful disease or injury is cured or reduced, brain tissue can regenerate. While we can’t guarantee that brain tissue will be restored, we offer here our simple, immediate and first step recommendations using non-prescription measures.

First, do you know the name and characteristics of the disease or injury that is causing your pain? Are you engaging in specific treatments to reduce or even cure your disease, or are you simply taking symptomatic pain relief medications? 

Start at least two herbal-botanical agents that have some clinical indications that they reduce inflammation in the brain and spinal cord: serrapeptase-palmitoylethanolamide (PEA) and astragalus-curcumin-luteolin-nanokinase. You can take different agents on different days. 

Increase the amount of protein (meat, fish, poultry, eggs) in your diet. Consider a collagen supplement. Limit starches and sugars. 

Start taking these vitamins and minerals:

• Vitamin C - 2,000mg in the AM & PM

• Vitamin B-12, Vitamin D

• Minerals: Magnesium and selenium

We recommend vitamins daily and minerals 3 to 5 days a week. 

The above will help you stop additional tissue loss and hopefully regenerate brain tissue.  

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on the treatment of intractable pain and arachnoiditis. This column is adapted from bulletins recently issued by the Arachnoiditis Research and Education Project and the Intractable Pain Syndrome Research and Education Project.

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

What’s Missing in ‘Elvis’ Movie: The King’s Chronic Illness

By Pat Anson, PNN Editor

There’s a scene towards the end of the new “Elvis” movie when you know the end is coming soon. Presley, as depicted by actor Austin Butler, collapses in a hallway minutes before being scheduled to take the stage at the International Hotel in Las Vegas.

Instead of rushing an unconscious Elvis to a hospital, manager Tom Parker --- played by a surprisingly villainous Tom Hanks -- declares that the show must go on and summons “Dr. Nick” to make it right. After a quick injection of stimulant drugs, Elvis recovers just enough to sing, dance and entertain an adoring crowd in a packed showroom.   

That one scene sums up how the real Elvis Presley spent his final years before dying of an apparent heart attack in 1977 at the young age of 42. Popping pills. Slurring his words. Deeply depressed. And driven to continue performing by “Colonel” Parker and others.

“They really tried to push Elvis beyond his capacity in the last few years of his life. He was disabled,” says Dr. Forest Tennant, a retired physician and pain management expert who is one of the last people alive to be intimately familiar with Elvis’ drug use and medical problems.

In 1981, Tennant was hired by an attorney for Dr. George Nichopoulos (Dr. Nick), who faced criminal charges in Presley’s death. Tennant reviewed the autopsy report, medical records and a confidential 161-page private investigation, and testified as a defense witness for Nichopoulos, who would be acquitted of charges of overprescribing drugs.

After the trial, Tennant remained curious about Elvis’ medical problems and continued his research while treating people with intractable pain. The knowledge and experience Tennant gained in the last 50 years led to his recent book, appropriately titled “The Strange Medical Saga of Elvis Presley.”  

Elvis did indeed suffer from heart problems aggravated by an excessive use of drugs, but Tennant believes the ultimate cause of his death was a connective tissue disorder called Ehlers-Danlos syndrome (EDS), a major cause of intractable pain and other chronic health problems.

A diagnostic screening tool for EDS didn’t exist when Elvis was alive and few physicians were even aware of the condition. But Tennant thinks Presley had all the symptoms of EDS, including an unusual degree of flexibility and double jointness that allowed him to swing his hips and gyrate wildly. Those sexy dance moves helped make Elvis famous, but they also foretold what lay in store for him.

“EDS is a genetic connective tissue collagen disorder, and what that means is that you are genetically predetermined to have your collagen in certain tissues either disappear or deteriorate or become defective, and to put it bluntly, you can have a rectal problem and an eye problem at the same time due to the same cause because your collagen is deteriorating in these tissues,” Tennant told my colleague Donna Gregory Burch in a 2021 interview. “If you get a severe case like Elvis Presley, your life is going to be very miserable, and you're going to die young unless you get vigorous treatments.”      

The day before he died, a dentist gave Presley codeine for an aching tooth, not realizing how sick he was or that codeine could cause his heart to stop. Elvis collapsed in the bathroom 24 hours later. His sudden death led to rumors that he died from an overdose or even a horrible case of constipation. The truth is more complex.

“Nothing happened to Elvis Presley that we don't have a good logical, scientific explanation for now. But certainly back in those days we didn't,” Tennant explained. “Elvis Presley had multiple diseases. He was terribly ill, and he died accidentally in some ways with a dentist giving him codeine for his bad tooth, and his bad teeth were also part of the same disease that gave him a bad colon and a bad eye and a bad liver. They were all connected.

“He had all these metabolic defects due to his genetics, and so the codeine built up in his system. He had this terrible heart, so he died suddenly, within seconds, as he was trying to sit on the commode.”

Fortunately, the “Elvis” movie spares us any final scenes like that – ending instead with actual clips from one of Presley’s last concerts. They show a tired and very sick man, aged beyond his years and sweating profusely. But he still sang like “The King.”

All proceeds from sales of “The Strange Medical Saga of Elvis Presley” go the Tennant Foundation, which gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.

Why Intractable Pain Treatment Requires a Stimulant

By Dr. Forest Tennant, PNN Columnist

In 1896, Dr. Henry Snow was the chief cancer surgeon at the Royal Brompton Hospital in London. He recognized and agonized over the immense pain and suffering of his patients when they developed constant pain and approached their end of life.

Dr. Snow wanted to relieve their suffering, so he administered the drugs that were available one at a time: morphine, cocaine and alcohol. With each he managed to get some pain relief, but didn’t obtain the relief he wanted and patients were still suffering. Not to be deterred, he made a profound discovery.

Dr. Snow mixed morphine and cocaine in liquid alcohol and administered the solution to his patients. Then he found formidable and humane pain relief. This three-drug mixture gave rise to the concept of “synergy of constituents,” which means that the simultaneous administration of multiple pain-relieving drugs added up to more than each one alone. In other words, two and two equaled six rather than four. 

The success of Dr. Snow’s discovery spread rapidly to other hospitals and countries, and became known as the “Brompton cocktail.” In France and elsewhere, physicians discovered they could add an antihistamine, antipsychotic or cannabis oil to the mixture and get even more pain relief.  

The Brompton cocktail was used until the 1970’s, when it gave way to the convenience of opioid tablets, capsules and injections, rather than the time and cost of making a liquid that contained multiple drugs. 

The Amphetamine Discovery 

Fortunately, after the demise of the Brompton cocktail, a handful of researchers weren’t about to forget the “synergy of constituents” and the pain-relieving potency of stimulants like cocaine. An example of the pain-relieving capability of stimulants is caffeine, which in the 1960’s was added to a variety of pain relievers such as aspirin and codeine to obtain synergy. 

Amphetamine was discovered in the 1930’s and promoted as “Benzedrine” to stay awake while driving. Because amphetamine produced alertness, it became known as a stimulant. Clinical reports began to surface in the 1940’s that amphetamine and its derivatives also helped depression, weight loss, mental alertness, hyperactivity and attention span. They soon began to be marketed and labeled for those conditions.  

Clinical studies on amphetamine derivatives for pain relief were finally started in the 1980’s, and they clearly showed that they provided a great deal of pain relief.  

By the time the last century folded, a core of pain researchers knew that not only cocaine but amphetamine derivatives such as methylphenidate and phentermine relieved pain. What they didn’t know was why. This answer was to come 15-20 years later. 

Stimulants Initially Rejected 

I became quite excited about the clinical trials that showed stimulants relieved pain, and in the late 1990’s gave a group of intractable pain patients the weak stimulant and weight loss drug phentermine, in combination with clonidine. The opioid dosages for these patients dropped 40 to 50 percent within six weeks and they got even better pain relief.

I presented my findings to colleagues at some national professional meetings. Much to my surprise, I was summarily informed that the new long-acting opioid formulations of the fentanyl patch (Duragesic), oxycodone (Oxycontin), morphine (MS Contin) and the implanted intrathecal (spine) opioid pump eliminated any need for stimulants or the concept of “synergy of constituents.”

By the turn of the century, the use of these new long-acting opioids and implanted opioid pumps became the standard of the day. Stimulants and their synergy were essentially forgotten, and they were rarely used for intractable pain again until about 2010. 

The Rebirth of Synergy 

After the year 2000, I don’t recall ever being referred an intractable pain patient who had not already been started on one of the long-acting opioids and/or an implanted opioid pump. They were referred to me simply because they were not getting adequate pain relief. Almost every one of these patients had found that their opioids quit working well, regardless of dosage or even if a second or third opioid was added to the mix.  

Somewhat out of desperation, about 12 years ago I recalled Dr. Snow, the Brompton cocktail and the “synergy of constituents.” I also remembered my study on phentermine and clonidine, so I started giving patients on opioids who were doing poorly my favorite stimulant, phentermine, or occasionally methylphenidate (Ritalin).  

Later the narcolepsy drug modafinil (Provigil) and a mixture of amphetamine salts (Adderall), came on the market. They too proved to be excellent “synergists” with opioids. I found that every intractable pain patient who received one of these stimulants not only got better pain relief and were either able to “hold the line” or reduce their opioid dosage.  

Phentermine continued to be my favorite stimulant to relieve pain and reduce the use of opioids because it additionally kept weight down and helped the patient keep moving and functional. 

Why Stimulants Work 

Although stimulants have been clinically known to relieve pain since Dr. Snow’s experiments in 1896, researchers didn’t provide us with the biologic “why” until recently. 

In the past decade, some outstanding researchers determined that there are about half a dozen different neurotransmitters in the brain and spinal cord that relieve pain. The three major neurotransmitters are endorphin, dopamine and gamma amino butyric acid (GABA). These neurotransmitters relieve pain by activating trigger points in the central nervous system called receptors. 

These astute researchers also determined that intractable pain may deplete endorphin, dopamine and GABA. Consequently, a substitute drug may have to be administered to obtain adequate pain relief.  

If you have constant, intractable pain, you may likely need the “synergy of constituents,” which will include an opioid, stimulant, and GABA substitute. Popular GABA substitutes include diazepam (Valium), carisoprodol (Soma), pregabalin (Lyrica), gabapentin (Neurontin), clonazepam (Klonopin), topiramate (Topomax) and alcohol. 

Which Patients Should Receive a Stimulant?

Stimulants have well-known abuse and addiction potential, so they should only be given to patients who have a well-documented disease or injury that is known to cause severe intractable pain. The most common diseases in this category are adhesive arachnoiditis, stroke or head trauma, reflex sympathetic dystrophy (RSD/CRPS), Ehlers-Danlos syndrome, and some autoimmune-collagen disorders.  

In most cases, patients who need a stimulant are clearly debilitated and require some family and caretaker support to function and carry out activities of daily living.  

Intractable pain patients have several dopamine substitutes available: 

• Amphetamine Salts (Adderall)

• Methylphenidate (Ritalin)

• Dextroamphetamine

• Phentermine

• Phendimetrazine

Misunderstood Objections

Many medical practitioners are not yet aware of the new research on stimulants and hesitate to prescribe them, even to needy, legitimate patients. The fear of abuse, diversion or dependence by the intractable pain or palliative care patient, while understandable, should not cause reluctance to prescribe a stimulant to these patients. No intractable pain patient will give away something that works so well.

In addition, the dosage of stimulants for pain relief is considerably lower than the usual level needed for abuse. Only small dosages are clinically needed in most cases and pharmacies today only issue limited quantities. Another safety factor in controlling adverse consequences of stimulants is that the severe intractable pain patient will usually have close family or caretaker support who can safely store and administer stimulants.

There is an unfounded fear of hypertension if a stimulant is prescribed. This is rarely the case, since the pain patient is dopamine deficient. A stimulant drug in an intractable pain patient may actually lower blood pressure since it may be elevated due to pain.

There is the belief that Adderall, Ritalin and some other stimulants are only for attention deficit hyperactivity disorder (ADHD). What is misunderstood is that ADHD is universal among intractable pain patients. Every person with intractable pain has reduced attention span, hypertension and agitation. One could argue that every intractable pain patient should be on a stimulant just for their ADHD. 

Dr. Snow and the Royal Brompton Hospital had the right idea. The severe, intractable pain patient needs an opioid to replace endorphin, a stimulant to replace dopamine, and a substitute for GABA.  

It’s time we bring back the “synergy of constituents” to humanely get better pain relief and simultaneously lower opioid dosages in the intractable pain patient. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his studies on the treatment of intractable pain through the Arachnoiditis Research and Education Project. A bibliography on stimulants for intractable pain treatment can be found here  

The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.   

Why Complicated Chronic Pain is Different

By Dr. Forest Tennant and Ingrid Hollis

As 2021 comes to a close, we wish to summarize what we personally consider to be the greatest issue in pain management. Physicians have observed for centuries that some chronic pain conditions are not only more severe than others, but some cause excruciating, constant pain that casts the poor suffering individual into a humbled, bed-bound state.

Unfortunately, throughout the past half-century or so, many concerned parties, whether intentional or not, have tried to lump all pain patients into one category, saying they all have persistent or chronic pain. This has led to calls for “one size fits all” treatment and inflated statistical figures on the number of pain patients who need help (i.e., 50 or 100 million Americans).

The Real Issue

Chronic pain has traditionally been defined as pain that continues past the normal healing time for an injury or disease, which is about ninety days. There has been no generally accepted separate classification as to the severity, constancy or periodicity of pain that lasts longer than 90 days. Consequently, chronic pain surveys and statistics always include persons with the common, mild to moderate painful afflictions such as bunions, carpal tunnel, fibromyalgia, headaches, TMJ, irritable bowel, back strains, plantar fasciitis, and mild neuropathies and arthropathies.

Cries of undertreatment of these common chronic pain problems ring hollow, since every community has a plethora of medical practitioners, pharmacies, health food stores and fitness centers that tend to vast number of persons who have these common pain problems.

It may also be why all of the recent lobbying and advocating for “chronic pain” doesn’t seem to connect with the body politic, because the vast majority of chronic pain patients are getting adequate care. This is not to say that treatment for their common, mild to moderate conditions can’t be improved, or that their treatment isn’t needed.

The real issue, however, is that there is a sub-set of chronic pain patients who develop what can justifiably be called “complicated chronic pain.” Most have tried a plethora of treatment options but are left with severe, constant pain that has a specific set of pathologic complications. It is this group that is undertreated, poorly understood and needs advocacy, attention and treatment for their complicated chronic pain.

The Complications

The hallmark of complicated chronic pain is constant pain which is associated with cardiovascular, metabolic and hormonal abnormalities. Complications include hypertension, tachycardia, glucose elevations (pre-diabetes, and diabetes), and adrenal-gonadal hormone deficiencies including cortisol, estradiol and testosterone, among others. These complications can lead to heart attack, stroke, heart failure, autoimmunity, diabetes, obesity, depression, dementia and other health problems.

Thanks to modern research and science, we have a better understanding of why some unfortunate individuals transform from a mild, periodic chronic pain, to a constant, ferocious and disabling pain state. We now know that injured or diseased tissue from whatever initiating cause can generate bioelectricity that may enter the spinal cord and brain -- the central nervous system (CNS) – causing destructive inflammation that damages critical tissue sites that normally eliminate or control pain.

This development is called “neuroinflammation.” The transformation process in now often called “centralization” or “central sensitization.” Some pain specialists prefer to call complicated chronic pain “neuropathic pain.”

We Need a Name

A syndrome is a clinical state in which one pathologic defect causes multiple abnormalities and symptoms. Hence, we recently began calling the complicated chronic pain state the Intractable Pain Syndrome (IPS). The term intractable was first used by British physicians in the last century who championed treatment of severe incurable pain. The term intractable is now used in some laws and is in popular use in some pain circles.

There may be a better name than Intractable Pain Syndrome. Maybe we should just call it “Complicated Chronic Pain.” Regardless, understanding that inflammation can develop in the CNS and cause complicated constant pain is essential, as these patients need a different treatment approach from the more common, uncomplicated chronic pain patient.

Going forward into 2022, we define Intractable Pain Syndrome as “an inflammatory disorder of the central nervous system that causes constant severe pain and is associated with cardiovascular, metabolic and hormonal complications.”

Furthermore, we will advocate that this tragic syndrome be understood, and that its proper treatment demands not only symptomatic pain relief, but specific treatment of the disease that originated the syndrome, along with specific treatment of its complications. 

Forest Tennant, MD, DrPH, is retired from clinical practice but continues his research on intractable pain and arachnoiditis. Ingrid Hollis chairs the editorial committee of the Tennant Foundation Research and Education Projects. She is also a family caregiver and advocate for those who suffer from rare diseases and intractable pain. The Tennant Foundation gives financial support to Pain News Network and sponsors PNN’s Patient Resources section.     

People in Pain Fight What Others Can’t Understand

By Carol Levy, PNN Columnist

“We are so fond of one another, because our ailments are the same.” Jonathan Swift.

That does not apply to those of us with chronic or intractable pain. Our “ailments” are different. Very different. Painful conditions caused by genetics, trauma, medical error or sheer bad luck. Many healthy people don’t know such pain can exist.

In the 1980's, organ transplant rejection was thought to be psychological. Then they learned that it is not in the mind. It is the body doing the rejecting.

Forty years later, many doctors still believe chronic pain is in the psyche. Hopefully, more are accepting that the mind is involved in chronic pain and helps determine how we respond to it, but it’s not where the pain originates.

As difficult as it is for us to accept persistent pain and the resultant disabilities, it makes it even harder when doctors, family, friends and colleagues say, “Oh, c'mon. It's not that bad. You just think it is. So you can think it into being better.”

Mindfulness, relaxation techniques and meditation are helpful -- to the mind. They help some of us deal with the pain, but most still need the benefit of opioids and other pain medications, treatments and physical therapy.

“I don't want my pain and struggle to make me a victim. I want my battle to make me someone else's hero.” Unknown author.

How often do we hear that? First usually comes the praise: “You are a true pain warrior.” Then the gut punch: “Your pain and struggle are such a good example to others who suffer. You should be grateful. That’s why you have the pain, to be an example.”

I'm sorry, but I don't want to be in pain every day so someone else can learn from my fight. It is a nice side benefit, but it is not why I fight the pain.

Chronic pain does make us different from others. We talk about it a lot, online and elsewhere. Cancer, diabetes, heart disease and other well-known illnesses -- people know and understand them. But Ehlers Danlos, CRPS, trigeminal neuralgia, arachnoiditis and other names too long to list are still the stranger in the room.

It is a struggle for us every day. We fight what others can't and don't want to understand.  Because it is a feared ailment once they know it exists.

Our fight is with us at all times, in whatever we do or try to do. It is daunting.

“Promise me you'll always remember: You're braver than you believe, and stronger than you seem, and smarter than you think.” A.A. Milne

Carol Jay Levy has lived with trigeminal neuralgia, a chronic facial pain disorder, for over 30 years. She is the author of “A Pained Life, A Chronic Pain Journey.”  Carol is the moderator of the Facebook support group “Women in Pain Awareness.” Her blog “The Pained Life” can be found here.