In PPM's 20th anniversary roundtable, pain practitioners share the good, the bad, and the ugly of the past two decades – but also offer a path forward.
Therapeutic and regulatory milestones in pain management – demonstrated in our anniversary timeline – have changed the landscape of chronic pain care for the past two decades, and the field continues to evolve in different directions. In honor of our 20th anniversary, PPM asked experts how they have witnessed the field change within their specialty since the year 2000 and where they see it headed. Here’s their take.
Pain treatment is centuries old, but not the “pain treatment industry,” which began about 20 years ago. The launching of the industry was vibrant. The exuberance was fueled with the 5 vital sign, new opioid formulations, and the epidural corticosteroid injection. Pain patients were finally getting some good care. Organized pain treatment establishments popped up everywhere, including at the Veteran’s hospitals, universities, and even rural areas. Professional organizations, self-help groups, publications, and research blossomed. Money was good. Growth of the industry was exponential.
Now that a generation has passed, the industry, like any other hyper-growth movement, is consolidating and organizing for the long haul.
Surprisingly, over the past two decades – since we launched PPM – little change in actual treatment at the clinical level has taken place until just the past few years. The industry is still quite reliant on opioids and epidural steroid injections (ESIs) – both of which have been associated with widespread tragedies.
Yet, there have been some profound research discoveries during this time as well, making the most recent 20-year history of pain treatment, in my view, quite remarkable. Millions of persons with pain and suffering have been helped.
Here is my short list of the positive changes.
First, the new agents to treat many rheumatoid and immunologic diseases, migraine headaches, and cancer have moved a lot of patients from the pain clinic to specialty medical practice. Those left behind are patients who suffer primarily from chronic, degenerative, traumatic, and genetic diseases.
Second, a new class of treatment drugs generally known as “neuropathic” agents have joined the two, long-standing treatment classes – opioids and anti-inflammatory agents. Gabapentin, duloxetine, and pregabalin are the best known of the new class. These agents operate by altering neurotransmitter levels at synapses and/or normalizing electrical conduction in neurons. There have been several less visible clinical advances including radiofrequency ablation techniques, prolotherapy, electromagnetic wave administration, hormonal treatments, and non-opioid analgesics such as low dose naltrexone and ketamine.
The public outcry regarding opioid abuse and ESI complications has tainted the reputation of pain treatment and pain practitioners, but the need for pain treatment is so great that patients will not be deterred. Also, these issues have obscured the progressive advances in pain treatment over 20 years, but the advances are here to stay. Both pharmacologic and interventional treatments had begun to reduce the need for opioids and injections long before the public become aware of these issues. At the same time, the need for these two basic treatments has not been directly replaced yet, since their need is still essential in many clinical situations.
Quietly, behind the scenes, some profound research has created the basis for pain treatment in the next 20 years. Severe chronic pain is now known to cause inflammation and tissue destruction inside the CNS, which not only produces constant pain but a syndrome of cardiovascular, endocrine, and immunologic abnormalities. Hormones referred to as neurosteroids are produced inside the CNS, suppressing neuroinflammation and promoting tissue healing (neuroregeneration). The discovery and realization of neuroinflammation and tissue destruction in the CNS – often called central sensitization these days – is fostering development of pharmacologic agents and clinical measures to prevent and treat neuroinflammation and severe pain.
The major disorders, both acquired and genetic, that cause severe pain have been identified, including adhesive arachnoiditis, CRPS/RSD, and genetic connective tissue disorders such as Ehlers-Danlos Syndrome.
This new information coupled with the advances of the past 20 years bodes well for the person who suffers from pain. Both practitioners and patients have the opportunity to look for simple, cheaper, more effective ways of doing things at the community level. We’ve had a great 20 years that has brought relief and recovery to millions. Additional positive progress is in the wind for the next 20.
See also, the IASP's 2020 rewrite of "pain".
Physical Medicine and Rehabilitation (PM&R) has changed significantly in the past 20 years – and continues to evolve as I write this, with the COVID pandemic pushing telemedicine and new approaches to patient care.
Every aspect of patient care from the first encounter to final care touchpoint has evolved with a much greater emphasis on patient perspective and experience. The role of the patient has changed as well with shared decision-making being the norm and a greater share of the responsibility for health status also shifting to patients.
Part of this is due to prevailing consumerism and growing patient expectations of healthcare systems, including transparency at all care levels. The physical therapy marketplace has responded to this transition by introducing technology that allows more patient interaction and control over the rehabilitation process. In addition, a greater emphasis has been placed on the home plan and self-care for therapy patients as less and less is being covered by third-party payors each year.
Unfortunately, increasing health insurance premiums – coupled with less actual health coverage – has been a trend in rehabilitation medicine. This environment is not optimal for breeding new and innovative interventions. On the other hand, we are seeing a medical device explosion (see our home-use guide to share with patients).
Exercise machine technology can now be powered by air pressure, making crucial physical activity much more palatable for the elderly and disabled. This new generation of exercise machines not only provide a vigorous muscular workout, but it does so with minimal joint stress, which is a large contributor to delayed onset muscle soreness. An easier and yet more effective workout that is completely electronically interfaced to capture all the nuances of the workout including sets, repetitions, and total work performed.
On the in-clinic side, electronic devices are becoming more sophisticated from a circuitry perspective. The use of artificial intelligence and machine learning algorithms enable the provider to focus on other aspects of patient care. We are also seeing more patients with implantable devices such as spinal cord stimulators and artificial joints, which have lowered overall therapy utilization and recovery times.
The focus has really been converging on data. The use of micro-electric mechanical technology (MEMS), for instance, has enabled real-time non-invasive dynamic monitoring of key biometrics, such as blood sugar in diabetes management. These integrated chips can sense specific ions and molecules in the body and will provide a constant stream of data to physician offices.
Combined with data generated from wearable technology, physicians have more data points on virtually any decision they need to make regarding a patient condition than they have had at any other point in history. More data combined with better algorithms should lead to more precise medicine and better outcomes – time will tell.
Back in 2000, only a few years after extended-release (ER) opioids became available, there was increasing enthusiasm for using opioids for chronic pain; many patients benefited as a result, but we all know how things progressed from there. Little was generally understood then about the impact of opioids on the body, about the nature of addiction, and the need for recognizing red flags and for doing risk assessment.
Once abuse-deterrent ER opioids became available, such as the reformulated OxyContin in 2010, and the number of opioid prescriptions in general decreased, prescription opioid street sales dropped, but, unexpectedly, opioid overdose deaths continued to increase, and still are steadily rising, as desperate patients and addicts turned to street drugs – basically heroin, increasingly laced with fentanyl. (See Dr. Schneider’s recent editorial on ER opioids.)
The situation worsened in 2016, when the CDC issued its problematic guidelines for chronic opioid use, resulting in ever-stricter state guidelines and regulations, often with confusion between whether an item was a guideline or required. One blatant example was the CDC guidelineto “carefully consider” if the daily opioid dose is to be increased to 90 MME; this led to a widespread mistaken belief that clinicians mustdecrease the total MME/day to 90 MME or face scrutiny by the patient’s family, other providers, pharmacists, and the medical boards.
As an addiction medicine specialist, it was evident to me throughout these years that a big part of the problem has been a lack of understanding by clinicians, patients, and regulators about addiction-related issues, resulting in inappropriate decisions and solutions, even in 2020. For example, ask yourself: If a group of patients without a prior addiction history are begun on opioids for chronic pain, what percent of them are likely to become addicted after 90 days: 5%? 50%? 90%? The correct answer, surprising to most people, is about 5% or less.
Here are the main areas in pain medicine that are still often misunderstood:
In the early years of pain management, there was insufficient attention paid to addiction and misuse; now the pendulum has swung to the other end and it’s time to rebalance.
Currently, prescribers are largely hesitant to prescribe opioids, while pharmacies are under pressure to reduce their supply of opioid medications. Solutions, including treatment for addicts, continue to focus on medications (especially naloxone) rather than on the whole patient.
While naloxone may prevent imminent opioid overdose death and is a useful part of medication-assisted treatment (MAT), it is only a first step. Part of the treatment plan must also include therapy to understand the underlying reasons for the addiction and strategies for healthier ways to cope with problems. Buprenorphine is increasingly being prescribed on a chronic basis as an effective part of MAT, often replacing the use of methadone which, in the past, played a similar role. But it too should be accompanied by behavioral health treatment. (see also, PPM’s literature review on addiction medicine and relapse prevention.)
I’ll end on a positive note – the recognition in recent years that patients with chronic pain as well as addicts need to be viewed as individuals. Both types of individuals often have a history (including childhood history) of some type of trauma, whether physical or emotional. Administering the Adverse Childhood Events (ACE) questionnaire can identify these patients and lead to individualized treatment plans including behavioral health treatment and trauma-informed care. The focus on biopsychosocial care has also encouraged patient education around the mind-body connection in these two (sometimes overlapping) disorders, that is, pain and addiction. Patients deserve explanations of the nature of addiction and the difference between addiction and physical dependence; such knowledge can combat the stigma experienced by too many people who assume that they are also addicts.
In 1996, I started practicing prolotherapy (short for proliferation therapy) with the only formula available then: dextrose. These regenerative injections stimulate the body to heal damaged joints and connective tissue. Simple as it was, dextrose prolotherapy worked amazingly well to reduce pain and increase function. When I asked Gustav Hemwall, MD, the oldest living prolotherapist at the time, why more physicians did not know of this simple, yet effective, treatment, he answered “because it’s too simple!”
Over the past 20 years, science and technology have surged, allowing more advanced prolotherapy formulas, making this “simple procedure” less simple. In the early part of the new millennium, for instance, the prolotherapist was introduced to platelet rich plasma (PRP). Many people have heard of PRP, but are not aware that when a joint area is injected with PRP, it is considered to be a form of prolotherapy. Essentially, prolotherapy is the technique; PRP is the formula.
Then, about 10 years ago, many prolotherapists started utilizing a formula of stem cell-rich tissue, taken from a patient’s own adipose (fat) or bone marrow, known as biocellular prolotherapy.
Each of these biologically active formulas used in regenerative orthopedic medicine have changed the face of clinical practice. With the further addition of diagnostic musculoskeletal ultrasound, more precise, targeted, enhanced treatments have become possible. And so, in the past 20 years, there has been a progression of technology in prolotherapy, analogous to what happened with telecommunications: first telegraph, then radio, then black-and-white television, then color television, and, now, digital streaming on demand.
However, despite the sophistication of advanced regenerative therapies, the prolotherapy physician must never forget the importance of spending the time to arrive at a correct diagnosis; that is the key to successful pain resolution, in this, or any, decade.
Although electrotherapy has been used for centuries, it was the 1966 introduction* of spinal cord (SCS) and transcutaneous electrical nerve stimulation (TENS) that sparked much wider interest.
By 1999, electrotherapy was being used to heal fractures, heal wounds, assist bladder control, cure tinnitus, advance acupuncture, treat hypertension, improve memory, and aid in virtually all types of pain management, including for fibromyalgia.
Then came my personal favorite: pulsed electromagnetic field frequency (PEMF). This technique has proved to be as important a tool for health and illness as penicillin was for infectious diseases. PEMF has been shown to increase ATP production, enhance the sodium-potassium pump, increase cellular pH, improve oxygen uptake, lower blood viscosity, build stronger bones, improve circulation/microcirculation as well as nutrient transport/waste elimination, and produce beta endorphins for pain relief.
While TENS is excellent for localized pain, PEMF affects every cell in the body, restoring the normal minus 70 mv charge on cells. And with Gamma PEMF, the technology has been said to put the brain/mind in a state of advanced Buddhist meditators, calming anxiety, relieving depression, and creating an optimal detached state of emotions in which the individual has no power or means to change the obvious stress.
In fact, I consider PEMF superior to many forms of psychotherapy. I have seen it improve memory and function in Alzheimer’s and Parkinson’s patients, as well as relieve pain that was resistant to opioid therapy, particularly diabetic neuropathic pain, while reversing sensory loss. In patients where I once recommended SCS, my first recommendation in the year 2020 is Gamma PEMF for most acute and chronic pain presentations.
*Dr. Shealy is credited with establishing the use of these interventions.
To know where we’re going, it helps to know where we’ve been. In the year 2000, 42.3 million households had at least one family member with a disability that limited individuals in the areas of self-care, mobility, activities of daily living, and more. For the years 1999-2002, chronic regional and widespread pain prevalence were reported at 11% and 3.6%, respectively. Women had higher odds than men for headache, abdominal pain, and chronic widespread pain.
Hispanic Americans had lower odds compared with non-Hispanic whites and Blacks for developing chronic back pain, leg/foot pain, arm/hand pain, and regional and widespread pain. One-third of Latina and Black families were located in the rural southern states. Nearly 45% of Hispanic families received income from Social Security with Medicare as the primary payor, while 12% had incomes from Supplemental Security Income and 6.5% had incomes derived from welfare payments from state or local governments with Medicaid as the primary healthcare payor.
At that time – two decades ago – only three models of care delivery were used:
The latter targeted outcomes associated with reduced medication use and emotional distress, improved healthcare utilization, management of iatrogenic consequences, return to work, improved activity levels, and closure of disability claims.
At least one major study documented demonstrable benefit to individuals and health costs associated with interventional pain programs over conventional and surgical models.4 Gold and Roberto, for instance, reviewed the literature on chronic pain in older adults from 1967 through 2000 to ascertain the nature of investigations into the impact of chronic pain. They found that research was focused primarily on the physical consequences of pain or functional outcomes, psychologic origins or consequences of pain, and social variables associated with pain, including race, gender, social network participation, family support, social activities, and employment.
By 2010, 60,500 US households with disabilities (aged 25 to 65-plus) rated their overall health as “fair to poor.” The number of households reliant on Medicare and Medicaid had grown to 2,166,000 households (18.7% of the population) – of these, 40% were dependent on VA healthcare, and 48% on Medicare or Medicaid, with the balance dually eligible for both Medicare and Medicaid.6
Pain-generating conditions associated with limitations of activity included HIV/AIDS, arthritis, musculoskeletal conditions, cancer, diabetes, spinal cord injury, organ impairment, renal and circulatory problems, and more. Women presented with pain at greater rates than men (19:17%), and Blacks were represented at greater rates than Hispanics (23.3:18.0%).
Do these numbers mean we doing the right things within the pain discipline? Not really.
In 2020, changes in the health characteristics associated with an aging population have created a care crisis in many communities; additional federal legislation (eg, SUPPORT Act, CARA) and state pain regulations are disrupting the delivery of pain care for all who interact with the systems of care.
Specifically, the influence of changes to contracting models, payor criteria, and population characteristics has affected delivery models, availability of the physician workforce, analysis of effectiveness, and service provision.
Importantly, in the intervening 20 years, we have not addressed the constructs identified by Gold and Roberto back in 2002. The payor-induced shift from integrated pain management to reliance on models poorly aligned with changes in the health characteristics of patients who are living longer with multiple chronic complex conditions has excluded this entire sector of the population from treatment. As payor models have narrowed and consolidation and specialization have increased, we’ve allowed the discipline of pain management to focus on shiny well-reimbursed technologies without addressing and promoting functional outcomes and psychologic consequences of these methods, or the social variables that support efficacious outcomes.
Acute pain care is markedly different than the treatment of complex illness with pain symptoms. Chronic pain research could be substantially improved if a systems-medicine approach were employed, combining both the study of body systems with psychosocial issues to address pain symptoms across the life course. Specifically, physicians must restore care models that implement a whole person-centered perspective as opposed to treating labels and payment criteria.
Let’s not waste our opportunities in the next 20 years to do things better.
Friedenstein first described bone marrow-derived MSCs in 1968, and Caplan later developed and described the culturing techniques utilized to form mesodermal phenotypes from these cells. Caplan coined the terminology “mesenchymal stem cells” and, more recently, promoted its revision to “medicinal signaling cells.”
Stem cell therapy in general has emerged as a field within pain medicine and orthopedics. An active area of research focuses on the science and applications of MSCs in pain medicine. These cells exist in the perivascular space of nearly all organs and are commonly sourced from a broad array of tissues such as bone marrow, adipose tissue, and umbilical cord tissue. Increasingly, it is appreciated that common analgesic mechanisms for MSCs depend on neuroimmune modulation, rather than on their multipotent differentiation capacity demonstrated in culture.
The efficacy of a variety of cellular therapies was examined in different animal models of clinical degenerative and neuropathic pain conditions after intravenous injection, intrathecal injection, or localized injection directly into the site of injury. These studies used cells sourced from mouse, rat, and human and demonstrated the analgesic effects of MSC treatment in a wide range of rodent models of neuropathic pain after nerve injury, spinal cord injury, streptozotocin-induced diabetic neuropathy, as well as degenerative arthritis pain. For example, a single intravenous or local (lesion site) injection of rat MSCs reversed mechanical allodynia in rats after tendon injury.
This anti-allodynic effect was blocked by the opioid receptor antagonist naloxone, suggesting endogenous opioid involvement. Sustained analgesia by MSCs appeared to require activation of central brain stem µ-opioid receptors and CXCL1/CXCR2 chemokine signaling. In vivo monocyte activation and immune interactions may underlie the long-lasting pain-relieving effects of MSCs.
Intrathecal administration is also becoming an effective way to deliver MSCs for long-term pain relief.A single intrathecal injection of MSCs provided rapid-acting, potent, and long-lasting pain relief for more than 6 weeks in mouse models of neuropathic pain. Dye-labeled MSCs migrated to the DRG and spinal cord meninges, where they survived for up to 3 months. After nerve ligation, the injured DRG neurons upregulated CXCL12, a chemotactic signal that guides MSCs to the damaged DRGs via a CXCR4/CXCL12 homing mechanism. TGF-1 secretion by MSCs was a specific mechanism conferring potent pain relief, as intrathecal administration of anti-TGF-beta-1 neutralizing antibody selectively reversed the analgesic effect. In addition, intrathecal MSCs effectively reduced nerve injury-induced neuroinflammation in the spinal cord, reflected by microglia and astrocyte activation and increased expression of IL-1-beta, IL-6, and TNF.
These observations were further confirmed and extended in experiments that demonstrated analgesic efficacy of MSCs from the bone marrow and from adipose tissue after either intrathecal or intravenous injection. The treatments reversed microglia and astrocyte activation, suggesting that MSCs may regulate immune cells and neurons by paracrine activity of TGF and IL-10. Notably, exosomes derived from human MSCs may serve as a cell-free therapy for nerve injury-induced neuropathic pain in rats. A single intrathecal injection of exosomes reversed mechanical and thermal hypersensitivities for 24 hours, and continuous infusion of exosomes into the intrathecal space prevented and reversed nerve ligation-induced pain for 2 weeks. The exosomes migrated specifically to the spinal dorsal horn, DRG, and peripheral axons associated with the ipsilateral nerve injury, and suppressed glial activation. Exosomes depressed TNF and IL-1β levels and reciprocally enhanced levels of IL-10, BDNF, and GDNF in DRGs with axonal injury.
As pain clinicians know, opioid tolerance is a primary driver for opioid dose escalation, overdose, and death in patients suffering from pain and patients suffering from addiction, contributing to the opioid epidemic in the US. MSC transplantation has shown efficacy in preventing and reversing opioid tolerance and opioid-induced hyperalgesia in rats and mice to date.When delivered prior to initiating daily morphine injections, MSC transplantation (intrathecal or intravenous) effectively prevented the development of opioid tolerance and opioid-induced hyperalgesia. MSCs further reversed opioid tolerance and opioid-induced hyperalgesia when delivered after they had been developed.
In addition to preclinical studies, MSCs have also shown promising results in clinical trials to treat pain associated with degenerative disc disease,, knee arthritis, and neuropathic conditions such as trigeminal neuralgia and pudendal neuralgia. Although intriguing, most of these studies can only be considered as preliminary due to limitations related to experimental design, sample size, source, quality control of MSCs, and heterogeneity of study populations. It is increasingly clear that MSC therapy needs ongoing mechanistic studies and rigorous clinical trials to better define the optimal indications, efficacy, safety, as well as sources, protocols, and processing of MSCs.
Clinical guidelines based on pre-clinical scientific research and clinical evidence must be established to provide a framework for decision-making in the application of MSC therapy. The potential to ameliorate symptoms and modulate disease processes with MSCs requires a conscientious and scientifically-driven approach to be fulfilled.
The past two decades have been like no other time in history from my point of view. The practice of medicine has changed significantly as the result of technological advances in treatments and steep shifts in the regulatory environment – both leading to longer life expectancy and exploding healthcare costs.
Game-changing events, for example, have included the passing of the Affordable Care Act (ACA), the broad adaptation of EMRs, the CDC’s 2016 guideline on prescribing opioids for chronic pain, and the implementation of the ICD-10 – with the ICD-11 set to take place in 2022. (See more game-changers in our 20-year pain management timeline.)
For pain practice, these shifts have placed a significant financial burden on the providers and imposed unfunded mandates causing administrative nightmares. I highlight just a few of the additional consequences I have seen below.
While humans are living longer, changes in dietary habits and lifestyle modifications have contributed to a significant increase in obesity, leading to more people suffering from degenerative joint and disk disease. These diseases have led to an epidemic of chronic pain in our elderly population. In fact, pain is among the top three reasons for healthcare visits in US (low back pain is number 1 – see PPM’s 2020 roundtable on back care consensus) and has become a major contributor to rising healthcare costs.
We may not all remember that the first decade of this century was often called the “decade of pain control.” Guidelines from the Joint Commission, state medical boards, and other regulatory agencies and professional societies were emerging like wildfire. Also around that time, news of cardiovascular adverse effects associated with NSAIDs led to a public health scare, limiting our therapeutic options for the management of chronic pain. This knowledge, combined with a broader acceptance of opioids at the time, led to the increased use of opioids as a mainstay of pain care.
Soon after, mandates stemming from the ACA focused a great deal on patient satisfaction and the use of quantitative measures, of which pain control was a key indicator. Widespread use of opioids in hospitals for acute and post-operative pain skyrocketed; “pill mills” proliferated, and patients flocked to pain clinics. Today, we remain in a public health emergency around opioid use and we are further tasked with maintaining pain care during the COVID pandemic.
While promising non-opioid therapies are in development and a variety of targeted interventional therapies are available for pain relief, we have to address the needs of our patients who trust us while also addressing the serious public health concerns of our society. On the positive side, actions of the past two decades have led to an expanded role for advanced practice providers (APPs) involved in pain care across specialties. This growing team approach and emerging focus on the biopsychosocial approach to pain management may be exactly what pain providers need to move up and out of the chasm.
To describe the change that we have seen as women in the field of pain management over the past 20 years in one word: incomparable.
Just as the field as a whole has advanced and progressed over the past two decades, so have the opportunities for women within our field. Trailblazers like Lisa Stearns, MD, a cancer-pain specialist who sadly passed away in May 2020, have transformed the space for female providers.
In the past 5 years alone, numerous societies have included women’s groups and committees, including the North American Neuromodulation Society’s Women in Neuromodulation (of which I am on the board) in 2015 and Women in Pain Medicine Special Interest Group (American Society of Regional Anesthesia and Pain Management) in 2017. In 2019, I helped found The Society of Women Innovators in Pain Management, which is dedicated to mentoring, supporting, educating, training, and developing future women influencers within the field.
Our industry counterparts have recognized the disproportionately low numbers of women working in advanced procedures and stepped up to assist with the creation of educational events and seminars for women in pain care as well. As a result, we have begun to see a rise in the involvement of women on society boards, journal editorship, and behind podiums. Our male counterparts have in many instances become advocates for women and made intentional efforts to include women in discussions around important topics within the field.
However, as recently as 2018, Dr. Tina Doshi’s article in Regional Anesthesia and Pain Medicine revealed that women make up only 18% of all pain physicians. (Editor’s Note: Dr. Doshi is a member of thePPMEditorial Advisory Board.)In fact, pain medicine ranks in the bottom quartile of medical specialties for women, only slightly above the stereotypically male-dominated training programs of orthopedic surgery (14%) and neurosurgery (17%). As a specialty, we have come far in many ways on the topic of gender equality, but there remains work to be done.
With the formation of networking and mentorship programs for women in the field and the examples being set by women throughout the world, I am confident that we will see more women entering pain management. With our male counterparts becoming fierce advocates for the unique components that women add to the discussions, we will continue to witness the transformation of the field for women to one of true equality. We must, however, continue the work that has been started to address systemic and implicit bias that still remains in some ways. I am grateful to play a small role in the transformation and feel hopeful and excited about the future of this amazing and dynamic field.
See also, how residents 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. Plus: Gudin and Fudin ask, have we done a 180 in pain care?