Orange is a new black: a short story about ketamine

Once upon a time, I started General Surgery rotation in urgent care. It was around 2am when we admitted a healthy muscular young fellow with perianal abscess. He needed a so-called I&D (incision and drainage), or, put it simply, to get the pus out. In 1986, not every surgical intervention required the attendance of an anesthetist. Nurses or medical students would take blood pressure and measure pulse and administer sedative drugs. My surgeon asked me, at that time, medical student,  to inject "Calypsol" a drug that I subsequently learnt had another name - ketamine. The surgeon explained the medication will allow him to make incision without knocking the patient completely out. The surgery went well, and after 15 min, we were on our way to the recovery room. Here things went unexpectedly odd. The patient became somewhat agitated, his muscles tensed, and he developed a visible erection.  He was mumbling something incomprehensible. Only after he woke up, he broke into a slew of emotional comments full of profanities and described vivid dreams, hallucinations and "out of body experience." 

Later in my work as an anesthetist, I used ketamine so often in trauma setting when an accidental drop of the blood pressure and depression of breathing were undesirable.  At that time, I already knew about "funny" sides of ketamine and always added medications to prevent or forget psychedelic experiences. 

Fast forward into my later years, we started using ketamine during and after surgeries for patients on high doses of opioids. It resulted in a dramatic decrease in morphine consumption and better pain control. 

My fourth and ongoing encounter with ketamine started one year ago. I finally overcame my skepticism related to reported miracles after ketamine infusions for chronic pain. As a matter of fact, I was familiar with publications concerning high-dose administration in an intensive care setting over several days for managing severe pain due to so-called Chronic Regional Pain Syndrome (CRPS). However, ketamine low-dose infusions in an ambulatory setting just did not sit well with me. Anyhow, after persuasion by colleagues and reading more literature, I tried it on a very carefully selected patient. I anxiously waited for her next appointment fearing to hear a horror movie story with hallucinations and other adventures. To my astonishment, the lady assured me that "it was the best experience" and her burning pain of the past 5 years disappeared. She also commented her mood and vitality have dramatically improved. Ever since I became a strong advocate for this therapy. In my experience, neuropathic pain (e.g., diabetic neuropathy, CRPS, phantom pain) is the most appropriate indication, following by a widespread fibromyalgia-type.  Even when the severity of pain remained the same, pain unpleasantness and other disturbing sensations tend to diminish.

Last but not least positive side effect is antidepressive. I do not treat depression, and when asked, send patients to mental health specialists. Nonetheless, chronic pain and depression are interwoven. Improved mood results in a decreased perception of suffering, gives more willpower for self-management and reactivation. 

Who would believe that the old drug with hallucinogenic properties similar to LSD and "magic mushrooms" will be a powerful remedy to fight chronic pain? 

Chronic Pain Syndrome vs Somatic Symptom Disorder

The College of Physicians and Surgeons of Ontario policy states that “physicians must only practice in the areas of medicine in which they are educated and experienced.”

Chronic Pain specialists are often encountering challenges related to the scope of practice in both clinical and legal fields. It is not surprising given the complexity of chronic pain, its biopsychosocial phenomena and interdisciplinary approaches.

In this essay, I will try to differentiate the two most commonly confused entities, Chronic Pain Syndrome and Somatic Symptom Disorder.

The diagnosis of chronic pain is based on syndrome analyses and recommendations of the International Association for the Study of Pain (IASP). The IASP defines pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” The definition of chronicity is not bound. Chronic pain was traditionally defined by the length of time that pain persists, but a time-based approach ignores many other essential features. Attempts to conceptualize resulted in more confusion. The IASP currently defines chronic pain as “pain without apparent biological value,” pain “that has persisted beyond the normal tissue healing time . . . as determined by common medical experience,” and (or) as “a persistent pain that is not amenable, as a rule, to treatments based upon specific remedies.”

The traditional view on the Chronic Pain Syndrome (CPS) is a presence of pathological conditions that for poorly understood reasons resulted in complex neuropsychological changes in the central nervous system leading to physical and emotional suffering and social dysfunction. The chronic pain syndrome construct was delineated in 1987 when it was argued that chronic pain syndrome, as opposed to chronic pain, “has the added component of certain recognizable psychological and socioeconomic influences.” The presence of at least four of the following eight characteristics was said, by the American Medical Association (AMA), to establish the diagnosis of chronic pain syndrome:

• Duration (more than six months)

• Dramatization

• Drugs

• Despair

• Disuse

• Dysfunction

• Diagnostic dilemma

• Dependence on others and/or on passive physical therapy

 The American Medical Association (AMA) stated that CPS has its origin in both iatrogenic factors, such as prolonged use of passive physiotherapy modalities and prolonged inactivation, and nomogenic factors (nomogenesis refers to abnormal illness behaviour functionally related to social legislation that rewards complaints of pain, suffering, and disability). CPS is a biopsychosocial chronic, and, in many cases, irreversible condition. Potentially noxious event, particularly if occurred in certain stressful situations (e.g., trauma, surgery, assault, motor vehicle accident), coupled with neuropsychological traits or overt psychopathology and amplified by social factors (e.g., low level of education, substance dependency, low income job) may create negative loop of suffering, pain behavior and disability. Pain is a function of brain, and in this construct the chronic pain syndrome is a disease of the central nervous system with its somatic (e.g., regional or diffuse pain, decreased range of motion,  sensory and motor abnormalities), psychological (e.g., depression, catastrophizing, poor sleep, personality changes, memory loss) and social (e.g., loss of income, social withdrawal) aspects. Conceivably, social contracts pay a significant role in the development and maintaining of the chronic pain syndrome. However, on the individual level, the affected individual has a lower quality of life than a patient with an acute myocardial infarct. This condition may result in complete vocational and social disability.

Although the AMA clearly stated that chronic pain syndrome does not constitute a psychiatric disorder, the diagnosis is often equated with the psychiatric diagnosis of pain disorder associated with psychological factors.

Notwithstanding the relevance of CPS as the diagnosis, in some instances, the biomechanical derangement cannot be defined based on the available clinical and other supporting evaluations. For example, low-velocity car accidents have minimal impact on the musculoskeletal system. These injuries have similar or less probability of creating severe lasting anatomical damage than a minor domestic mishap. However, the context is different, which by itself may trigger subsequent development of widespread pain and psychological symptoms. To address this conundrum, the American Psychiatric Association (APA), introduced Somatic Symptom Disorder (SSD) with predominant Pain into DSM-V. SSD was previously known as Pain Disorder or Somatization Disorder. Here are the actual diagnostic criteria as set out on page 311 of DSM-5:

Somatic Symptom Disorder 300.82 Diagnostic Criteria

A.  One or more somatic symptoms that are distressing or result in significant disruption of daily life. B.  Excessive thoughts, feelings, or behaviours related to the somatic symptoms or associated health concerns as manifested by at least one of the following:

Disproportionate and persistent thoughts about the seriousness of one’s symptoms.

Persistently high level of anxiety about health or symptoms.

Excessive time and energy devoted to these symptoms or health concerns.

C.  Although anyone somatic symptom may not be continuously present, the state of being symptomatic is persistent (typically more than six months).

With predominant pain (previously pain disorder): This specifier is for individuals whose somatic symptoms predominantly involve pain.

The similarity between CPS and SSD is evident. Both conditions are related to chronic regional or widespread pain that is disproportional to the inciting event or illness and includes psychosocial problems and dysfunction.

As a chronic pain specialist, I encounter and treat patients with either CPS or SSD. In many cases, the approach is similar and encompasses regular meetings and counselling, careful pharmacological management and allied health support (e.g., sleep hygiene, nutritional advice, alleviation of fear to inflict more damage with exercises). While interventional approaches may be considered in CPS, only after addressing psychosocial burdens, these methods are contraindicated for SSD patients. Invasive procedures reinforce negative beliefs related to somatic complaints and fixation.

Generally speaking, a presence or absence of anatomical problem can differentiate CPS from SSD. CPS includes a significant biomechanical component (e.g., subluxation of the cervical facet joint, herniated lumbar disc) that was not adequately and effectively treated on acute or subacute stages and, therefore, progressed into biopsychosocial derangement. SSD is a mental health condition that has maladaptive behavioural expressions. It is a diagnosis by exclusion of other possible medical and/or mental disorders. Although a chronic pain specialist may and should offer help to these patients, expert opinion and therapeutic input of a psychologist and/or psychiatrist is invaluable for both clinical and medicolegal purposes.

Nerve Blocks :(

Anytime people talk about "pain clinic" this issue keeps coming up. For a reason, unbeknownst to me, patients are expected to submit themselves to needling. Often these injections are performed weekly yet providing either no or very short-term pain relief. For the sake of argument, a placebo effect will not be discussed here, although, indeed there is a lot to do with the so-called expectations and other behavioural effects.

Physiologically, injected local anesthetics (hopefully, without corticosteroids) produce some pleasant warming numbness and muscle relaxation. Rarely, they offer long-lasting pain relief, but the mechanism is not clear. We can speculate that when these drugs are injected very close to the target nerve, or into the nerve, they cause neurotoxicity (poisoning) and slowing conduction of electric impulses through this nerve. There is another hypothesis of a so-called "pain reset," some magical Microsoft-like solution: if something doesn't work, and you don't know what to do, just click "restart." There is also a strong belief that with repeated nerve blocks, the pain will be diminishing. All these hypotheses have never been experimentally confirmed. On the other hand, tissue toxicity was documented in laboratory studies, and conscientious, ethical pain physicians published their experience disproving nerve injections (Arne Johansson and Bengt Sjolund. J Pain Symptom Manage 1996).

Thus, nerve blocks are rarely effective, their scientific level of evidence is undetermined, but sure enough, there is an ugly there. There is an inconvenient truth related to a fee for services system where doctors are paid per injection. Because, a single injection is not paid well, they do 6-12 needle punctures, injecting various unrelated and not united by sound diagnosis anatomical structures. I hope some doctors do this because they believe in this ritual. They were educated by older and imminent needle jockeys and genuinely considered "drill-mill" to be an equivalent of Pain Medicine. Maybe they are just blessed with ignorance? Otherwise, it must be greed. I refuse to believe they apply "My Mom's Principle" but instead shovelling a fundamental principle, "Do No Harm" into the deepest drawer. The excuse is always the same: "it is common practice, and everyone is doing it." This is true, but is it right?

Surprisingly, the regulations are very forgiving, and in the absence of evidence against this, multiple no sense injections are considered the standard of care. All that is needed is to obtain a permit specifically allowing clinics to implement these injections in their practice. Interestingly, no special permission is required for other procedures, such as joint aspirations. Perhaps, if someone comes with a swollen knee, offering injection in the neck, elbow and shoulder would be odd. However, when the low back hurts, no one asks why 10-12 injections are being performed including remote nerve blocks.

We always say our Canadian system is not ideal, but at least we don't do unnecessary treatments as Americans do. Well, in this case, our system is much worse. Certainly, some American doctors may also turn patients into pincushions to fill their bank accounts. However, the practice of multiple frequent injections is discouraged. There have been cases when doctors ended up in jail for Medicare fraud. The American Society of Anesthesiologists recommended against nerve blocks for chronic pain other than for diagnostic purposes a long time ago. In the absence of a similar position here, when nonsense declared as appropriate and medically necessary, and authorities turn a blind eye, patients must be vigilant and critical.

Medicolegal Expert

Let’s face an inconvenient truth: there are no independent medicolegal experts. We, physicians, are paid by either the plaintiff or defence to produce our medical opinions. We are called to remain impartial and nonpartisan. It contradicts human nature. People respond to incentives, and doctors are not immune to this. Even in seemingly transparent academic endeavours, financial incentives play a significant role. Numerous studies and literature reviews show a substantial influence of industry, with a correlation found between funding by the manufacturers and findings that show positive results for efficacy and safety of the benefactor’s products.

Why lawyers have an opportunity to take one's side, but experts can’t? It’s okay to be part of a team, either in daily life or even in court. Even a judge may implicitly sympathize with an accused perpetrator. Empathy or antipathy cannot be rationalized. We endlessly connect with other people because we are social creatures. Thus, if we were programmed to like someone and dislike another based on individual synaptic connections in our cortex, how we are supposed to act when the main reward center in our brain is involved? When a doctor is paid, the amygdala (e.g., Reward Centre) is pleased. Moreover, it will work hard to receive the same reward all over again and make everything possible to eliminate obstacles in this process.

The ethical standards should stand safeguards and suppress the rewarding circuit. However, when ethics are vague in politics, society, culture and religion, why doctors are expected to remain immune, especially when a personal report does not threaten anyone’s life?

The solution is logical and straightforward. Doctors, like attorneys, should be allowed to defend their clients. In the absence of any other superior judgment, courts and mediators should unravel medical casuistic the same way they deal with other legal matters.

My expertise is Chronic Pain, and because pain experience is personal and cannot be measured the same way as the blood pressure or cholesterol level, people are perceived not trustful. Granted, malingerers and con artists are out there, but what would be a reason for any human being to retreat from personal and social life, and hide in a cocoon of suffering if they are not indeed suffering. The reason for such horrific consequences may be different, including the expected compensation, but it will be very naive and mechanistic to assign all physical, emotional and social decline to one cause.

As an Expert, I have been following a simple rule to deal with convoluted issues: trust the patient unless evidence proved otherwise.

Peripheral Nerve Stimulation for Nerve Injuries

Peripheral Nerve Stimulation (PNS) method is older than any other neuromodulation technique. Pioneers of PNS experimented on themselves stimulating their infraorbital nerves, and achieving pleasant numbness in the face. Here is how they described the first treatment: "On October 9, 1965, Dr. Wall and one of us (Dr. W.H. Sweet) implanted a pair of silastic ring platinum electrodes around the ulnar and another pair around the median nerve in the arm carrying the wires out of the skin at the mid-forearm. On the median nerve 0.1- ms pulses at 100/s and 0.6 V provoked a pleasant tingling in the lateral three fingers and corresponding hand and stopped the pain in the medial three fingers and hand as well as tenderness in the third finger and palm."
White JC, Sweet WH: Pain and the Neurosurgeon:  A Forty-Year Experience. Springfield, Thomas, 1969, pp 894–899.

I started using PNS to treat intractable pain 15 years ago. Since I moved back to Canada in 2013, I have done only R&D work to develop new devices. Three of them are already FDA approved, and Health Canada approval is pending. 

I'm excited to have this modality here to make patients' lives better.

One of my patients from Seattle sent me this note a couple of weeks ago: Hello Dr. Gofeld. I'm the patient that you implanted the IPG into the calf of my leg to alleviate nerve pain in my left ankle. The nerve damage occurred during an ankle replacement. You SAVED my life!! Remembering how desperate I was for some solution, remembering being sent to you after a couple different appointments at the U of W, remembering the day that you told me, "I think I can help you". You don't know the impact your care of me had on my life and those around me! At this time, yes, I still use my IPG on a regular basis. My ankle tells me when to turn it on/off..........I find that so interesting. I just really want you to know that you're thought of and I am an eternally grateful former patient of yours. Sincerely, Sue Q"

Pain Specialist, eh?

A pain specialist, a specialist in chronic pain management, an algologist - all these and other definitions of a doctor who deals with individuals suffering from chronic pain do not make sense for the public. Does a family physician treat chronic pain? Yes, of course, as well as orthopedic surgeons, neurologists, oncologists, and the rest of medical specialties. Even dermatologists and ophthalmologists. So what makes this Pain Medicine special? Why can't each and everyone manage the pain of her/his patients? Perhaps, my view is unconventional, but I believe in accountability and commitment to patient well-being. If my esteemed colleagues did the same, many chronic pain conditions would be extinguished. For example, if spine surgeons would commit to staying with their patients, no surgeries for low back pain would ever happen. The reality is different: patients are promised miracles and cure, and then are thrown away back to their family doctors loaded with narcotics and more pain issues than before the surgery. But, let me come back to definitions.

Chronic Pain Specialist is the one who should be finally able to make a correct anatomically sound diagnosis and treat the problem. Unfortunately, patients get to us after months and often years of physical and, subsequently, emotional suffering. When a clear bio-anatomical cause is not addressed, pain is transformed brain of the sufferer, starting off a vicious cycle of pain-depression-social isolation-drug dependency-pain. Therefore, we, Pain Specialists, should have seen patients with sciatica, acute back and neck pain, and other conditions, way before orthopedic and other surgeons; we should have consulted patients with shingles and traumatic nerve injuries before it is too late. Pain Specialists should be seen as a new Palliative Care model. Just until recently, only dying cancer patients would be referred to Palliative team. With the paradigm shift, these patients are being routinely assessed by palliative care doctors to address their symptoms - pain, fatigue, constipation, etc. It resulted not only in better care, but in significant improvements in the quality of life and, often, survival.