Recent and ongoing studies continue to shed new light on the mechanisms responsible for joint pain in in both inflammatory and degenerative arthritis, leading researchers toward new pathways and new targets for novel therapies to relieve disability and distress in patients with osteoarthritis (OA) and rheumatoid arthritis (RA).
“Pain is what bothers people most and is what they seek medical help for; however, the current treatments for arthritis pain are limited in the sense that they typically don’t eliminate pain—they may take the edge off it but they don’t eliminate it,” said David Walsh, PhD, FRCP, Professor of Rheumatology and Director of the Arthritis Research UK Pain Centre at the University of Nottingham.
“The treatments we have now are also limited in that they are often associated with significant side effects,” he said. “Recent advances in our understanding of pain mechanisms, though, have led to a number of possible new treatments that could be game-changers in this field for patients.”
Dr. Walsh will discuss the mechanisms of pain activation in OA and the potential for new treatments during the session Pain in OA and RA: From Basic Mechanisms to Pain Phenotypes, which will have its first viewing with a live question-and-answer period on Friday, Nov. 6, from 4 – 5 p.m. EST. Registered attendees have on-demand access to watch a replay of the session through Wednesday, March 11.
“There is a lot of research going on, and our understanding of pain is miles ahead of what it was just a few years ago, which is leading to real advances,” Dr. Walsh said. “This research is helping us to better understand the mechanisms of pain and the molecules that are mediating it.”
That understanding, he said, has led to what could be the first new analgesic medication in decades—one that works through a completely different mechanism than anything currently in use. The potential treatment involves blocking nerve growth factor (NGF), a molecule that has been shown to be crucial to the mechanism that drives OA pain.
“NGF is involved in sensitization rather than normal protective pain, and the evidence we have from studying a number of different blocking antibodies in humans, suggests that it contributes a significant amount to the pain that people with OA experience,” Dr. Walsh said. “Unfortunately, one of the consequences of anti-NGF therapy is that it also has different side effects and different risks than existing treatments, so whether and how this can ultimately help people with arthritis pain will depend on balancing those risks against the benefits an individual can get from it.”
Camilla Svensson, PhD, MSc, Professor of Cellular and Molecular Pain Physiology at Karolinska Institutet in Stockholm, Sweden, will review immune-mediated pain mechanisms in inflammatory arthritis and findings from emerging studies that point to the potential for new therapies.
“The cause of joint pain in RA has traditionally been attributed to the inflammatory process in the joint, but it is becoming increasingly clear that other mechanisms are also at play,” Dr. Svensson said. “Recent findings from my and others’ laboratories, for example, are demonstrating how immune complex can directly activate nociceptors and how antibody-driven joint inflammation can impact the activity of osteoclasts and satellite glial cells and how these cells can influence the excitability of sensory neurons.”
New research involving the interphase between the rheumatology and pain fields continues to identify new avenues to explore and, in her presentation, Dr. Svensson will provide an update on some of the findings reported from preclinical work using animal models that are frequently employed in studies of RA pathology.
“For example, recent study findings have suggested that receptors for immune complex are expressed on pain neurons and seem to play an important role in pain hypersensitivity in several animal models of antibody-induced arthritis,” she said. “This represents a new way of ‘interaction’ between the innate immune system and the nervous system.”
Other findings have shown that persistent pain-related behavior without joint swelling is associated with changes in dorsal root ganglia macrophage and satellite glial cell number, and a dysregulation of both lipid mediators and cytokines in those cells contributes to mechanisms that play a key role in arthritis joint pain dissociated from joint swelling.
“We still have a long way to go when it comes to uncovering the interactions between the immune system, both innate and adaptive, and the sensory nervous system that lead to pain chronicity,” Dr. Svensson said. “Increasing mechanistic understanding of the cell-cell interactions occurring and the mediators involved in development and maintenance of joint pain will hopefully lead to identification of new pain-reliving therapeutic strategies.”