New Directions in Pain Treatment

New Directions in the Treatment of Chronic Pain | Pharmacy & Therapeutics Community | Feb 2016

The IOM’s 2011 publication, Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research, succeeded in bringing attention to the long-underappreciated problem of pain.

The publication acknowledged that an underfunding of research was a significant barrier to progress, with only about 1% of a National Institutes of Health (NIH) budget

Relabeling pain a “biopsychosocial” phenomenon, the report urged a new recognition of its complex, multidimensional nature, as well as the wide range of individual variations in susceptibility to pain, cultural and emotional interpretations of pain, and responses to treatment.  

One eagerly awaited legacy of the IOM report is the soon-to-be-released final draft of the National Pain Strategy (NPS), which the NIH has described as a comprehensive population health–level strategy for pain prevention, treatment, management, and research. It contains recommendations for coordinating the efforts of government agencies and public–private partnerships to improve pain assessment and management programs throughout the country.

Any kind of “private” partnership immediately makes profit the top priority instead of health care.

“The goal of the National Pain Strategy is to provide patient-centered, interdisciplinary care that is compassionate, well informed, and individualized to every patient who is experiencing pain,” says Sean Mackey, MD, PhD, Chief of the Division of Pain Medicine at Stanford University

In partnership with the NIH, and in response to objectives outlined in the IOM report and the NPS, researchers at the Stanford Systems Neuroscience and Pain Laboratory (SNAPL) have established the Collaborative Health Outcomes Information Registry (CHOIR), an open-source platform that will be used to collect much-needed outcomes data on large numbers of patients suffering from chronic pain.

“One of our primary interests right now is in the development of brain-based biomarkers,” Dr. Mackey says.

“Biomarkers hold a great deal of promise in helping us to better understand how to distinguish pain from not-pain. Perhaps just as important, they are an integral part of the developing field of neuroprognosis—a field that eventually will allow us to predict whether an individual is more likely to respond to one treatment compared with another.”

Scientists want to make pain measurable so doctors can be certain about the patient’s pain existence and amount. On the positive side, this will then allow them to determine (and defend) their decisions about the best treatments.

Yet, such a device, when pushed to market, will then have the power to declare us either as pained or pain-free, and anything we might say to the  contrary will be completely ignored.

I’m not comfortable with a machine scan of my brain having the final word on how much pain I’m feeling.

Researchers at Dr. Mackey’s lab also are examining novel pharmacological approaches to the treatment of pain, which may help to provide patients and clinicians with alternatives to treatment with opioids.

The Pain Epidemic Versus the Opioid Crisis

While the U.S. pursues new approaches to the treatment of pain, problems associated with the use of opioid analgesics persist and have led to considerable divisiveness in this country.

Recent editorials on this topic have described antagonism between two principal groups—a cautious majority of experts, well aware of the drawbacks of opioids but intent on taking a measured approach to the problem, and a minority who seem intent on sharply curtailing the use of these drugs despite potentially disastrous consequences.

Discord between these groups grew more pronounced after the September 2015 release of draft guidelines for prescribing opioids by the Centers for Disease Control and Prevention (CDC).5

“Some of the recommendations in the draft document are quite strong and were made with a lack of supporting evidence,” Dr. Webster says. 

“The recommendation, for example, that prescriptions not exceed the equivalent of 90 mg of morphine is unsupportable. There is no evidence that patients cannot be safely placed on more than this amount of the drug. Furthermore, there are millions of Americans who are currently taking this drug for much-needed pain relief.”

The author of The Painful Truth (2015), a new book that documents personal and physical struggles of individuals suffering from pain, Dr. Webster says that he receives calls or emails at least weekly from patients in chronic pain who are panicked because their doctors are suddenly refusing to continue their long-time treatment with opioids.

With the constant stream of negative and unbalanced information about opioids in the media, he adds, doctors have become increasingly afraid even to treat people in pain.

“I think the consequences of these guidelines are potentially serious, without any foundational evidence for the recommendations they contain,”

Recategorizing Pain While Exploring Novel Targets

The search for compounds that are safer than opioids and yet can provide significant pain relief to fairly broad patient populations will require new ways of defining pain—a recategorization that is more in line with an individualized approach to pain management.

clinical trial inclusion criteria frequently do not produce patient populations that are ideal for meaningfully testing a particular treatment.

Accordingly, the field is moving away from categories of pain—such as those based on a particular diagnosis, injury, or anatomic location—that have proven to have limited utility in clinical research.

“Unfortunately, in medical school, and even in residency and beyond, what is still being taught are the standard categories of pain [Table 3].

There is still a tendency to think in terms of nociceptive versus neuropathic pain, for example. And this oversimplification ignores a great deal of what we already understand about the nervous system,” Dr. Argoff says.

Researchers and clinicians are increasingly turning their focus toward the identification of pain phenotypes,25,26 which incorporate detailed descriptions of pain (e.g., burning, stabbing, pricking, shooting) as well as specific clinical signs and information, such as the results of quantitative sensory testing

Ultimately the identification of pain phenotypes should enable researchers and clinicians to better address underlying neural mechanisms of pain. While this is an exciting area of research, it is still relatively new;

In another compelling area of pain research, a wide range of studies is more closely examining the changes that the central nervous system undergoes in response to pain, and how these changes affect both the brain and the entire body.

Pain is not just a local phenomenon,” Dr. Argoff says. “If an individual has pain, even localized pain—let’s say an arthritic knee—that persists for any reason, that person’s central nervous system will continue to receive ongoing information about pain transmission, and eventually may begin to learn to process that information much more quickly and more efficiently.”

Depending upon genetic, environmental, and other unique influences, an individual’s nervous system may become primed to have a heightened response to new painful stimuli—and in some cases, even to stimuli that are not typically regarded as painful

Researchers are examining the degree to which such “learning” by the nervous system, or strengthening of connections among nerve cells, plays a role in the transition from acute pain to chronic pain.

As knowledge of signaling mechanisms, receptors, and pathways involved in the pathophysiology of pain deepens, researchers are identifying a variety of novel targets that may lead to more effective treatments for pain (Table 4). Among those currently attracting intense interest are voltage-gated sodium channels, which have been proven to play a significant role in the processing of pain

Among notable compounds under investigation that may lead to similarly targeted pain relief are inhibitors of nerve growth factor,63 calcitonin generelated peptide (CGRP) antibodies,64 and interleukin-6 inhibitors65 (Table 4).

While the list of potential targets is expanding rapidly, researchers continue to face considerable hurdles in the translation of analgesic efficacy from animal models to humans.

A growing trend toward personalized medicine in the field of pain research has intensified efforts to improve the ability to predict whether a particular individual will respond to a given treatment.

While pain treatments with broad indications would certainly have value, Dr. Argoff says, it is unlikely that a new compound would effectively treat most individuals with pain.

“It’s essential to develop affordable and standardized processes for determining who is likely to respond to a treatment, so that patients will suffer less by not having to experience failures. It doesn’t matter to me if 80% of patients in a study responded to a new compound. What matters to me is whether the patient in front of me responds.”

An Integrated Approach to Undertreatment of Pain

While patients and clinicians await the development of more effective drugs to treat pain, many patients continue to receive ineffective treatments or are unable to gain access to appropriate treatments.

“The undertreatment of pain is a huge problem,” says Richard Payne, MD, Professor of Medicine and Divinity at Duke University,

Undertreatment of pain can be traced to a wide range of factors

These include a lack of communication between patients and clinicians, a lack of knowledge about pain and its treatment on the part of both patients and providers, and stigma associated with suffering from pain and with medications taken to treat pain

“Nonpharmacologic treatments, such as behavioral approaches to pain management, are an essential component of any comprehensive pain program, but are simply not always available to patients who need them, or to physicians who wish to prescribe them,”

This is a huge health policy failure, because we have data to show that comprehensive approaches—the integration of physical, behavioral, social, and medical approaches—actually do work.

Re-establishing, promoting, and sustaining such multidisciplinary care would help address the undertreatment of pain and also put a lot less pressure on physicians to prescribe opioids. Opioids are often the default treatment because they are readily available and frequently inexpensive.

Further research, they hope, will generate the data necessary to support the use of these treatments.

Data collection so far has been limited, partly because until recently pain was not seen as a disease in its own right, but rather as a symptom of a wide range of other diseases

This explains the lack of funds for pain research: pain is only researched as one of many symptoms of many diseases which get separate funding.

Consequently, pain as a therapeutic area has lacked its own institution or home within the NIH, as well as means for centralized data collection

“I also look forward to reports by CMS [the Centers for Medicare and Medicaid Services] on current demonstration projects that are assessing the efficacy of multidisciplinary pain clinics.

Data from these reports may encourage Medicare and other payers to begin paying for these services.

The treatment of pain will improve when patients begin to have access to a whole range of treatments designed to improve their psychological and physical functioning.”

This article has informative tables at the end:

  • Table 1: Selected Current Nonopioid Treatments for Chronic Pain
  • Table 2: Selected New Opioid Formulations Under Investigation for Acute and Chronic Pain
  • Table 3: Selected Pain Terminology
  • Table 4: Selected Emerging Nonopioid Treatments for Acute and Chronic Pain

PDF version: ptj4102107.pdf

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