Researchers Develop Targeted Approach to Separate Pain Relief from Inflammation in NSAIDs

Scientists at the NYU Pain Research Center are making significant strides in understanding the mechanisms behind pain and inflammation. Their recent study, published in Nature Communications, highlights a key receptor—EP2—in prostaglandins, the hormone-like substances involved in pain signaling. Unlike the previously believed main receptor EP4, the EP2 receptor has been identified as primarily responsible for mediating pain without influencing inflammation.

This discovery was achieved through focused research on Schwann cells, which are vital in peripheral nerve function and play roles in conditions like migraine and other pain syndromes. The researchers found that blocking the EP2 receptor in these cells effectively abolished pain responses in mice while allowing the inflammatory process—a natural and essential immune response—to proceed normally.

Traditionally, NSAIDs such as ibuprofen and aspirin work by inhibiting enzymes that produce prostaglandins, thereby reducing both pain and inflammation. However, long-term use of NSAIDs can pose risks, including gastrointestinal damage, bleeding, and cardiovascular or renal issues. The new insights suggest that selectively targeting the EP2 receptor might offer a refined pain management strategy that bypasses these adverse effects.

The study further demonstrated that activating the EP2 receptor in human and mouse Schwann cells sustains pain signals independently of inflammatory responses. This indicates that drugs designed to antagonize the EP2 receptor could potentially treat pain efficiently while sparing the beneficial effects of inflammation.

Currently, the research team is exploring the development of targeted therapies that block EP2 receptors locally—such as in joints affected by arthritis—to provide pain relief without systemic side effects. This approach underscores the potential for creating more precise pain treatments, possibly offering alternatives to NSAIDs that are both safer and more effective.

Overall, these findings mark an important advance in pain research, highlighting how the decoupling of pain from inflammation could revolutionize future analgesic treatments and improve patient outcomes.