Summary: Researchers have found a whole new way of managing chronic pain. Blocking neuropilin-1 (NRP1) receptors may shut off the pain caused by nerve growth factor. It does this without losing the good that nerve growth factor does.
There may be hundreds of painkillers, but most work the same way. Most common painkillers belong to one group: non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs are good for mild to moderate pain. They block the enzymes that cause inflammation.
But NSAIDs may not work well for some severe pain. They also do little for neuropathic (nerve) pain, chronic pain, and more.
So doctors often turn to opioids for chronic or severe pain. These drugs act on pain receptors in the brain. But they are not very picky. They also hit other receptors, and that causes side effects.
In short, for all these painkillers, there is still a big gap. Some kinds of pain are hard to manage, like chronic pain, nerve pain, and other severe pain. This is why services like interventional pain management St. Louis look for new ways to address these problems.
So researchers are looking for other ways to manage pain. Science still does not fully know how pain travels to the brain. But that is changing fast, and the picture gets clearer every year.
New studies have found many pain receptors. Nerve growth factors seem to switch these receptors on. Nerve growth factors play a significant role in chronic pain, such as in people with arthritis.
But the body also needs nerve growth factor to grow and heal nerves. So blocking this chemical outright is not an option. It would do more harm than good.
Nerve growth factor acts on different receptors. Some help healing. Others cause pain. So researchers want to block the pain receptors and leave the helpful ones alone. Now they seem to have found one such receptor, and a way to block it.
Blocking receptors is a common way to adjust how the body works. For example, blocking certain receptors can stop the harm from too much histamine, such as allergic reactions.
The upside of blocking a receptor is that you keep a chemical’s good effects and block only its harm. In this new approach, researchers want to keep the good effects of nerve growth factors and block the pain.
This is not the first try at blocking pain receptors. Earlier, researchers blocked a receptor called tropomyosin receptor kinase A, or TrkA, and it worked well. Blocking TrkA receptors eases pain. But blocking TrkA also slows healing. In the end it may make arthritis worse. That is why researchers had to stop testing drugs that block TrkA.
Now the latest study reports a safer way to block the pain from nerve growth factor. The researchers found a receptor called neuropilin-1 (NRP1). Blocking it seems to shut off pain alone. The good effects of nerve growth factor stay intact.
In long-lasting painful conditions like arthritis, the body keeps making nerve growth factor to heal. It also keeps causing pain. New studies show that blocking NRP1 stops only the pain, not the good effects.
Better still, researchers have found peptides (short protein chains) that block NRP1 well. They appear safe for clinical use.
These are still findings from pre-clinical studies. Researchers are now testing peptides to block this new receptor, NRP1. They still need to find a safe way that works. Even so, these findings bring hope to people with chronic pain. Science may be close to a new class of painkillers. They could ease chronic pain as well as opioids do, and be much safer. Chronic pain specialists are likely to use these new tools to help patients more.
Frequently asked questions
What is the NRP1 receptor, and what does it have to do with pain?
Neuropilin-1, or NRP1, is a receptor that nerve growth factor acts on. Nerve growth factor has two jobs. It helps nerves grow and heal, and it also drives pain. Researchers found that blocking NRP1 shuts off the pain from nerve growth factor. Its healing effects stay. That makes NRP1 a new target for treating chronic pain.
Why does nerve growth factor cause chronic pain?
Nerve growth factor switches on pain receptors. In long-lasting painful conditions such as arthritis, the body keeps making nerve growth factor to heal. The same chemical keeps causing pain. Blocking it fully would do more harm than good, because nerves need it to grow and heal. The goal is to block only the receptors that carry its pain signal.
Why were TrkA pain drugs stopped?
Researchers first tried blocking a receptor called tropomyosin receptor kinase A, or TrkA. It worked against pain. But it also slowed healing and could make arthritis worse in the end. That is why testing of TrkA-blocking drugs was stopped. The newer NRP1 approach aims to block pain and leave the healing effects of nerve growth factor intact.
When will NRP1 pain medicines be available?
Not yet. These are findings from preclinical studies. Researchers have found peptides that block NRP1 and appear safe for clinical use. They are now testing them. They still need to prove a safe way that works in people. If they succeed, we could get a new class of painkillers for chronic pain. It would be much safer than opioids.
Source:
Peach, C. J., Tonello, R., Damo, E., Gomez, K., Calderon-Rivera, A., Bruni, R., Bansia, H., Maile, L., Manu, A.-M., Hahn, H., Thomsen, A. R. B., Schmidt, B. L., Davidson, S., Georges, A. des, Khanna, R., & Bunnett, N. W. (2024). NEUROPILIN-1 INHIBITION SUPPRESSES NERVE-GROWTH FACTOR SIGNALING AND NOCICEPTION IN PAIN MODELS. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI183873
Dr. Gurpreet Singh Padda, MD, MBA, MHP
