Recent Findings in Pain Research
Scientists at the NYU Pain Research Center have successfully identified a specific receptor in prostaglandins—the hormone-like substances targeted by common painkillers—that induces pain without causing inflammation. These findings, published in the journal Nature Communications, have significant implications for the development of more selective pain medications with fewer side effects.
The Relationship Between Pain and Inflammation
“Inflammation and pain are typically viewed as interconnected phenomena. However, the ability to block pain while allowing inflammation—an essential process for healing—to occur represents a critical advancement in pain management,” stated study author Nigel Bunnett, professor and chair of the Department of Molecular Pathobiology at NYU College of Dentistry, and a faculty member of the NYU Pain Research Center.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
Non-steroidal anti-inflammatory drugs (NSAIDs) rank among the most frequently consumed medications globally, with an estimated 30 billion doses administered annually in the United States alone. Available both over the counter (e.g., ibuprofen, aspirin) and via prescription, NSAIDs are widely utilized in managing pain and inflammation. However, their long-term use carries significant risks, including gastrointestinal damage, increased bleeding, and adverse effects on heart, kidney, and liver function.
Understanding Prostaglandins and Their Receptors
NSAIDs function by inhibiting enzymes that produce prostaglandins, thereby reducing levels of both prostaglandins and inflammation. While it is commonly believed that eliminating inflammation addresses pain, inflammation plays a protective role as it signifies the immune system’s response to injury or infection.
“Inflammation serves a beneficial purpose by aiding in repair and restoring normal function,” remarked Pierangelo Geppetti, adjunct professor at the NYU Pain Research Center and professor emeritus at the University of Florence. “Using NSAIDs to inhibit inflammation could inadvertently prolong healing and recovery from pain. A more effective approach to managing prostaglandin-mediated pain would involve selectively alleviating pain while preserving inflammation’s protective properties.”
Targeting the EP2 Receptor
In their study, the researchers concentrated on prostaglandin E2 (PGE2), a key mediator of inflammatory pain released by Schwann cells—specialized cells within the peripheral nervous system that are implicated in migraine and other pain conditions.
PGE2 interacts with four distinct receptors, with previous studies by Geppetti indicating that the EP4 receptor is primarily responsible for inflammatory pain. However, the recent research identified that the EP2 receptor plays a significant role in mediating pain without influencing inflammation. Targeted delivery of drugs to selectively inhibit the EP2 receptor in Schwann cells successfully eliminated pain responses in mice while allowing inflammation to proceed normally.
“To our considerable surprise, blocking the EP2 receptor in Schwann cells eradicated prostaglandin-mediated pain while allowing inflammation to progress as usual. This finding effectively separates the pain response from inflammation,” explained Geppetti.
Future Directions in Pain Management
Further investigations in human and mouse Schwann cells revealed that activating the EP2 receptor triggers a signal that perpetuates pain responses through pathways that are independent of inflammation, confirming EP2’s sole role in pain. “The antagonism of this targetable receptor could therefore offer a means of controlling pain without the negative side effects associated with NSAIDs,” noted Bunnett.
The research team continues to conduct preclinical studies to evaluate how drugs aimed at the EP2 receptor may be utilized in the treatment of pain associated with conditions like arthritis, which are typically managed with NSAIDs. Geppetti emphasized, “Selective EP2 receptor antagonists have considerable potential. While more research is necessary to assess side effects, particularly regarding systemic administration, local targeting—such as injections into a knee joint—shows promise.”
Key Health Takeaway
This research highlights the potential for developing pain relief strategies that effectively distinguish between pain and inflammation, paving the way for more targeted pain management approaches that minimize adverse side effects.
The study was conducted by Bunnett, Geppetti, and their collaborators, including Raquel Tonello, Chloe Peach, Dane Jensen, and Brian Schmidt from NYU, alongside Romina Nassini, Francesco De Logu, Lorenzo Landini, Matilde Marini from the University of Florence, Jin Zhang from the University of California, San Diego, and Giulia Brancolini of FloNext, co-founded by Geppetti. The research received funding from several sources, including the National Institutes of Health and the European Research Council.
