THE OFFICIAL NEWS SOURCE OF ACR CONVERGENCE 2022 • NOVEMBER 10-14



Chronic pain challenges require some changes in thinking

William Maixner, DDS, PhD
William Maixner, DDS, PhD

The Tuesday afternoon lecture Genetics of Chronic Pain will focus on what has become a public health problem affecting, by one estimate, a quarter of Americans.

William Maixner, DDS, PhD, Director of the Center for Translational Pain Medicine at Duke University, and the President-elect of the American Pain Society, focuses on biological, environmental, and genetic factors involved in pain transmission and modulation. The session starts at 1:00 pm in Room 5 B and will present current translational research with a focus on the role of genetics. With a background in dentistry and pharmacology, Dr. Maixner has led large cohort studies on common chronic pain conditions such as temporomandibular disorder (TMD), and says that much that has been learned about pain processing in TMD also applies to musculoskeletal pain conditions such as fibromyalgia.

Dr. Maixner challenges clinicians to rethink the way they view patients with chronic pain.

“When I think of a pain patient, I think of that patient almost as a kaleidoscope of signs and symptoms,” through which factors such as physical changes, environment exposures, as well as psychological distress, are expressed, he said.

“The body and consciousness (self) begin to change over time,” said Dr. Maixner, adding that “the kaleidoscope is controlled by the up-regulation or down-regulation of genes that are intrinsic and unique to the individual and regulated by environmental exposures.”

In turn, the by-products of genes, proteins, influence a variety of biochemical cascades that influence the kaleidoscope of signs and symptoms assessed in the clinic.

Comorbidity has been the rule rather than the exception, said Dr. Maixner, noting that it is unusual for a patient presenting with chronic pain to have only one condition. Clustering methodology enables clinicians to look at common pathways to pain conditions.

“One of the constructs we use to sub-classify patients with chronic pain is how well the individual perceives sensory events in their environment,” Dr. Maixner said. “This is a domain that has not been well studied, but we think it is an important predictor.”

One fallacy that Dr. Maixner will address is the notion that chronic pain is “all in your head.”

“The idea that there is a distinction between mind and body is erroneous, given that pain is a result of known and unknown neurobiological processes,” he said.

The new methodology to diagnosing and stratifying pain patients according to genetic architecture has led to reverse-translating pharmacology, which is revealing new therapies as well as repurposing old therapies. Beta-blockers, traditionally used in treating cardiovascular disease, have been found to be effective. Similarly, EGFR, a member of the ErbB family of tyrosine kinase receptors, has received attention for its therapeutic potential against pain. EGFR inhibition is the first-line treatment for non-small cell lung cancer, and a number of case reports suggest that EGFR inhibition provides rapid relief of cancer pain.

No discussion of chronic pain management would be complete without mentioning the use of opioids’ “oftentimes appropriate use but sometimes inappropriate use,” Dr. Maixner said.

While the lay press and policymakers have much to say about widespread opioid addiction, Dr. Maixner sees two “interwoven epidemics,” the opioid epidemic and the chronic pain epidemic. The latter affects up to 100 million people, yet receives little public awareness. Also, clinicians’ reliance on inadequate pain management tools has led to the inappropriate exposure of too many people to opioids.

Discovery offers a path to resolve both epidemics, Dr. Maixner said. Research has uncovered a new class of mu-opioid receptors that may prove to be more effective than the old standbys.

“We’re really at the verge of developing a whole new concept in the way we diagnose pain patients,” Dr. Maixner said. “By focusing less on the anatomical site-specific diagnoses and more on diagnoses based on mechanisms, clinicians will have better tools for addressing pain.”