Researchers have identified a novel way to block pain signals, paving the way for better medications to treat chronic pain.
Every year, one in five Americans reach for nonsteroidal anti-inflammatory drugs (NSAIDs) for headaches, arthritis, sprains, menstrual cramps and other types of pain.
The drugs, sold under brand names including Advil, Aleve and Motrin, block the receptors COX-1 and COX-2, which produce prostaglandins. Found in virtually every tissue in the body, prostaglandins react to pain by producing inflammation.
While lowering excessive amounts of inflammation helps stop pain signals, small amounts of inflammation are crucial for helping the body fight off infections and heal from injuries.
This means taking an NSAID not only eases pain but also reduces essential inflammation the body needs.
Researchers at NYU Pain Research Center in New York City, however, discovered how to target prostaglandin-producing receptors without eliminating vital inflammation.
In a new study, the researchers looked specifically at prostaglandin E2 (PGE2) in Schwann cells, which are found outside the brain in the peripheral nervous system.
This system is a network of nerves connecting the brain and spinal cord to the rest of the body and Schwann cells are thought to be behind migraine pain.
Researchers in New York City are testing the effects of pain relievers that target pain but not inflammation, which is needed in small doses for healing and fighting off infections (stock image)
The researchers said drugs that target pain but not inflammation would reduce the need for NSAIDs, which are sold under brand names like Advil (stock image)
They found PGE2 has four different receptors. Of those, the team found that EP2 specifically is responsible for pain.
They then used unspecified pre-clinical drugs on mice to target just the EP2 receptor. This reduced pain without affecting inflammation.
Pierangelo Geppetti, study author and adjunct professor at the NYU Pain Research Center, said: ‘Inflammation can be good for you – it repairs and restores normal function.
‘Inhibiting inflammation with NSAIDs may delay healing and could delay recovery from pain. A better strategy to treat prostaglandin-mediated pain would be to selectively reduce the pain without affecting inflammation’s protective actions.’
The discovery comes amid a rift in the scientific community regarding another pain reliever, acetaminophen.
President Donald Trump earlier this week tied the pain reliever acetaminophen, sold under the brand name Tylenol, during pregnancy to an increased risk of a child developing autism, despite inconclusive evidence.
The new study, published Thursday in the journal Nature Communications, looked at samples of human Schwann cells to determine which receptors to target.
Looking at mouse models, the team found injecting pre-clinical drugs, or those that are being studied but are not available to the public, into mice reduced their pain levels while leaving inflammation untouched.
Geppetti said: ‘To our great surprise, blocking the EP2 receptor in Schwann cells abolished prostaglandin-mediated pain but the inflammation took its normal course. We effectively decoupled the inflammation from the pain.’
The study findings come days after President Donald Trump (pictured here with health secretary Robert F Kennedy Jr) tied pain reliever acetaminophen to autism
Acetaminophen is sold under the brand name Tylenol, as well as other over-the-counter medications like Benadryl (stock image)
Developing drugs that only target EP2 would effectively eliminate the need for NSAIDs, which make up 30billion doses in the US every year.
And long-term NSAID use has also been tied to gastrointestinal and kidney damage, so the researchers believe moving away from NSAIDs would help reduce these risks.
Prostaglandins also stimulate the production of a protective mucus lining in the stomach, so a reduction in all prostaglandins – which occurs when NSAIDs target all receptors, not just the one that controls pain – wears away at that layer and leaves the stomach lining vulnerable to acid and other contaminants.
NSAIDs also reduce blood flow to the gastrointestinal tract, which makes it harder for the stomach lining to repair itself. Blood flow to the kidneys is also reduced, which hampers function over time.
It’s unclear which specific drugs the researchers used in the study and when they might be available to the public.
Geppetti said: ‘Selective EP2 receptor antagonists could be very useful. While more research is needed on side effects, especially with giving a drug systemically as a pill, targeted administration that acts locally on an area like a knee joint holds promise.’
