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19 Articles in Volume 20, Issue #4
20/20 with Dr. Nathaniel Katz: Pain Research and Future Therapeutics
A 20-Year Timeline: Pain Therapeutics and Regulations
A Comparison of the Alpha-2-Adrenergic Receptor Agonists for Managing Opioid Withdrawal
A Pain Assessment Primer
After the Task Force: A Conversation with Vanila A. Singh, MD
Ask the PharmD: Can opioids and benzodiazepines ever be used together?
Cognitive Strategies and Mindful Awareness for Integrative Pain Care
COVID: Clinical Considerations for Acute and Post-Infection Symptoms
Editorial: Fudin and Gudin Tackle Pain Care History – Asking, Have We Done a 180?
From Hands-On to Home-Based Care: Physical Therapy Undergoes a Paradigm Shift Due to Pandemic
MS-Related Pain and Spasticity: Are Cannabinoids an Option?
New Biological Agents for Psoriatic Arthritis: A Monoclonal Antibody Primer
Pandemic Presents Unexpected Opportunity to Embrace Multimodal Analgesia and the Integrative Care Team
Provider Perspective on Knee OA: Injections and RFA Options
Redefining the “Pain Specialist” of Today
Resident’s Corner: Climbing the Learning Curve in Pain Management
The Evolution of Pain Management: Experts Weigh In
Tips from the Field: How to Enhance Practice Efficiency
Tumor Necrosis Factor (TNF) Inhibitors: A Clinical Primer

Editorial: Fudin and Gudin Tackle Pain Care History – Asking, Have We Done a 180?

As PPM celebrates 20 years, our editors-at-large share their own clinical journeys and how their theories around chronic pain, pain management, mental health, and care teams have nearly come full circle.

A commentary from PPM's Co-Editors-at-Large


Dr. Jeff Gudin’s Perspective

Nearly 25 years of treating, researching, and often living with chronic pain, most would consider me an expert. Unfortunately, the more I learn about pain, the less I realize we as a scientific community actually know.

Thinking of the diverse pathogenesis of this complex syndrome we call pain reminds me of a recent article in PPM on chronic low back pain, in which we attempted to pool some consensus around treatment approaches. How is it that brilliant minds from different specialties can all disagree on how to best treat the number 1 patient complaint in America, and what does that mean for our specialty?

My theories about chronic pain have vacillated over the years. In my early residency, I thought my specialty was rather simple; I was able to explain to most patients with somatic or neuropathic pain that there was some injury, irritation or inflammation to some well-defined structure, whether it visceral, musculoskeletal, peripheral nerve, nerve root or spinal cord/brain-derived. Almost every patient had some structure or nerve that we could target or inject to relieve their pain. The patients that did not fit this theory simply had psychogenic pain for which no interventional modalities would benefit [I think there is a lesson here for many new interventional pain graduates, but that’s a story for another day! In the meantime, check out our new Resident’s Corner column.]

I credit my fellowship and early practice years’ pain theories to my colleague and previous mentor at Yale: Dr. Mark Thimineur.  He was destined to determine the root pathophysiologic cause of pain and was one of the brightest research minds I have encountered. It is disappointing that his 1998 paper on complex regional pain syndrome (CRPS) published in the  Clinical Journal of Pain didn’t make more of a splash in the pain community. Mark did (and taught me how to perform) the most detailed neurological examination of pain patients that I have ever seen, including during academic neurology rotations. He recognized early on a pattern of sensory, reflex, coordination, and motor strength abnormalities in patients with CRPS, and devised a brilliant assessment paradigm using quantitative strength testing equipment, quantitative sensory testing, cranial nerve and reflex assessments.

We studied nearly 150 CRPS patients and found nearly half with abnormalities of spinothalamic, trigeminothalamic and corticospinal dysfunction. This incredible research would set the stage for the remainder of my career, recognizing that CAT scans and MRIs are simply images and tell us nothing about function. I would explain to patients it’s like looking at a broken circuit breaker from the outside – all looks okay but clearly dysfunctional.

As a young practitioner still, it became clear to me that there was no cure for what we call “chronic pain” and I continued to refine my theories on the pathogenesis of pain. I would explain to patients that some trauma or imbalance in their mid-brains has changed the way they process pain messages so that even low-level pain signals get amplified to cause local or regional hyperalgesia – the old “Fibromyalgia Syndrome” theory. (See Dr. Goldenberg’s current take on fibro as a neuropathic pain disorder).

Over the years, I began to recognize the common bidirectional relationship and overlap between chronic pain and mental health disorders. Data support that approximately 1 in 5 US adults experience mental illness each year. And it was readily apparent that more than half of the patients in my chronic pain clinic were on antidepressants, anxiolytics, or other medications to treat psychiatric conditions. Here is where the “chicken or egg” debate in my brain began to blossom. Why was it that the driven CEO, athlete, or single parent could conquer their disease and the patient with even the slightest mental health condition could fall to pieces with chronic pain. I began to accept and preach something I had overlooked for many years ­– the importance of psychological and cognitive behavioral interventions. Although the term has fallen out of fashion, pain “catastrophizing” (now being renamed by Dr. Darnall’s group at Stanford) was a real phenomenon – a maladaptive response to pain that amplified chronic pain intensity and distress.

Add to the above that the only class of medications we had to treat severe levels of pain was a medication that caused misuse, abuse, addiction and overdose deaths related to respiratory depression – and it’s no surprise the crises that ensued. The literature has clearly demonstrated that for patients with mental health conditions there is an associated increase in receiving high-dose opioid regimens. These patients often have compulsive pill-taking behavior; mix that with an analgesic that has only partial efficacy leading to increased and early repeat dosing, and we can easily account for many of the unintentional deaths.

So, what’s the correct answer going forward? As is typical, it is probably a combination of all of the above. Something goes awry in our central nervous system, and each of us has the innate ability to fend off this attack. Whether it’s inflammation, glial cell modification, or any one of the thousands of neurogenically active substances contributing to the symptoms of physical and emotional distress- it is clearly a complex process that requires a multimodal approach. As most interventionalists have realized, injections don’t cure chronic pain patients. We hope that each of the psychological, medical and interventional modalities lowers pain levels enough to improve function and quality of life. (See the IASP's 2020 rewrite of "pain".)

Dr. Fudin and I started a column in PPM called “Analgesics of the Future” just over a year ago to give our readers some inights and hope for treatments on the horizon. There have been incredible advances made in drug delivery and electrical stimulation devices, ion channel modulators, and even plasmid DNA vectors encoding for some of the body’s natural analgesic and defense mechanisms. These advances truly give me hope that the future for patients suffering with chronic pain is bright and that we will eventually conquer this disease as we have many other. Until then, we must continue to offer patients access to complementary, pharmacological, interventional and cognitive behavioral therapies.

Over the years, Dr. Gudin and Dr. Fudin have recognized the bidirectional relationship between chronic pain and mental health disorders and the need for team-based care.


Dr. Jeffrey Fudin’s Perspective

Akin to Dr. Gudin’s reality check, I have seen several changes over the past 20 years. These include the explosion of polypharmacy to treat pain (or anything for that matter), over- and under-prescribing of opioids, collaborative efforts and enhanced reverence within and among various practicing clinicians, expanded knowledge of pain pathophysiology with commensurate targeted pharmacology, and, of course, the explosion of biologics, particularly for inflammatory diseases and headache treatments in the pain space.

My father spent his entire career as a community pharmacist, and I can remember him telling me when I was in pharmacy school that, over his professional career, things had changed such that greater than 75% of all medications he dispensed didn’t exist when he attended college, and that many represented new pharmacologic classes. Generics were frowned upon, and in fact discouraged to the point that most states disallowed any mention of the brand name on a generic drug label (such as, “This drug is comparable to ABC”).  And, prescription drug sampling to community pharmacies for initiation of new therapies was commonplace.

Marijuana was illegal, amphetamines could be purchased without a prescription, and all pharmacies looked forward to compounding unique prescriptions for individualized therapy, pharmacogenetics was just a concept, and the list goes on. One thing that has always stuck with me was his mantra that with the professional came a commitment for lifelong dedication to patient care and learning. Boy, was he right!

Fast-forward to the year 2020. In today’s world of chronic pain, it’s easy to be cynical and label chronic pain patients that require long-term opioid therapy as malingerers or addicts.  And unfortunately, the media and even many clinicians who wish to avoid liability or conflict make that an easy road on which to travel. Notwithstanding, all of us have an obligation to patients to display sympathy and empathy. We must understand the difference, and if a patient is going down a slippery slope of addiction to opioids (as opposed to disease progression or opioid physical dependence), that requires responsiveness, compassion, and counseling.  The empathetic ability to understand and share the feelings of another, and the sympathetic heartfelt understanding of pity and sorrow for someone else's misfortune has never been more flagrant as seen in the face of our current COVID-19 pandemic. The isolation and frequent abandonment of patients with chronic pain and others with a true opioid use disorder are rampant throughout the United States.

Years ago, I believe that pharmacists were less worried about opioid addiction or misuse, although diversion was common and they always had a “corresponding responsibility” to the prescriber in terms of opioid dispensing. But over the past two decades, the pharmacy profession has continued to migrate from a prevailing dispensing role to one of clinical expertise in complex pharmacotherapeutics. Many pharmacists have become an integral part of the integrated healthcare team. This burgeoning role has placed pharmacists – much like advanced practice providers (fellow board member Theresa Mallick Searle has been covering their experience for PPM) – smack in the middle of drug development, managed care decision-making, the hospital bedside, and in collaborative clinics with nurses, nurse practitioners, physicians, physician assistants, behavioral health specialists, and others.

It is clear today that the complexity of medication therapeutics has morphed way beyond the bailiwick or expertise of any one prescriber or even the pharmacist, as the latter already have specialty residency training in various therapeutic areas such as pain management, behavioral health, infectious disease, etc. Consideration of individualized patient therapeutics, drug selection based on important drug interactions and/or patient phenotype, navigating the complexities of insurance coverage and prior authorizations are no doubt overwhelming for any prescribing providers, and as such has vitalized the importance of a team medicine approach to include pharmacist clinicians.

Consider for example clinical pharmacy specialists (CPS) that practice with the Department of Veterans Affairs or Defense, or in the Public Health Service.  In these settings, CPSs use validated tools to assess patients for risk of opioid abuse or misuse, quantify risk of opioid-induced respiratory depression, screen for depression, adjust and/or prescribe medications. More specifically, they determine if the patient should or should not be on an opioid (and if so, is it the right one or do they need help transitioning to another one); stratify various risks; prescribe or recommend in-home naloxone; recommend, monitor, and interpret urine drug screens, medication blood levels, and pharmacogenetic tests; anticipate otherwise unanticipated drug interactions due to metabolisms and/or p-glycoproteins; cost-effectively select the best medication based on insurance coverage; review entire medication profile and make recommendations with a focus on pain therapeutics – I could go on and on. Imagine the expertise offered and time saved to clinicians that are less invested in, less qualified, or have less time to complete these tasks.

Moving forward, I envision specialty pharmacies that employ full-time pharmacists to fill a collaborative role in direct patient care onsite in community pharmacies as well as in clinics.  In these roles, pharmacists will complete complex medication and pharmacokinetic assessments, order appropriate laboratory tests (pharmacogenetics, toxicology, general chemistry and blood panels) that may dictate medication section and adjustments, and they will prescribe under collaborative agreements. This  evolution will free up time for physicians and physician extenders to meet with patients and focus on diagnostic assessments and it will allow individualized medication therapeutics to thrive and advance to an unimaginable level. In short, the future of pain management insofar as medication management is concerned will require an entire neighborhood of providers all working in concert for the best patient outcomes.


More on Pain Management’s Evolution

See also, our 20-year timeline on game-changing pain therapeutics and policies, how practitionersresidents and advanced practice providers are navigating the pain management learning curve and what pain research icon Nathanial Katz, MD, thinks about future therapeutics in our 20/20 Side Chat series.

For patient perspectives, see our Q&A with the U.S. Pain Foundation's Cindy Steinberg and our report on voices from the opioid crisis.

Last updated on: August 14, 2020
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