Acetaminophen Suppresses Pain Transmission Before It Arrives at the Brain
Revised Article:
Title: Paracetamol's Peripheral Pain-Blocking Secret Unveiled
Catch a glimpse of the fascinating world where common painkiller paracetamol (acetaminophen, Tylenol®, or Panadol®) does more than just tame brain-bound pain. Researchers from the Hebrew University of Jerusalem have unearthed a groundbreaking mechanism that reveals paracetamol's ability to shut down pain at its source: the peripheral nerves.
The study, led by Profs. Alexander Binshtok and Avi Priel, challenges the long-held belief that paracetamol solely operates in the brain and spinal cord. Their research, published in esteemed journal PNAS (Proceedings of the National Academy of Sciences USA), showcases a previously undiscovered peripheral method by which paracetamol relieves agony.
This intriguing revelation revolves around a compound named AM404, produced by the body after a dose of paracetamol. The team discovered AM404's production within pain-sensing nerve endings, where itblocks sodium channels responsible for transmitting pain, deactivating the signal before it reaches the brain.
"This marks the first time we've demonstrated that AM404 works directly on the nerves outside the brain," said Prof. Binshtok. "It reshapes our entire understanding of how paracetamol subdues pain."
This innovative finding opens doors for future pain relief. As AM404 targets only the nerves that carry pain, it could potentially minimize common side effects such as numbness, muscle weakness, and those associated with traditional local anesthetics.
"With the development of new drugs based on AM404," added Prof. Priel, "we might finally deliver pain treatments that are highly effective, yet safer and more precise."
More on this Neuropharmacology Research News
Authors: Danae MarxSource: Hebrew University of JerusalemContact: Danae Marx - Hebrew University of JerusalemImage: Courtesy of our website
Original Research: Closed access."The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels" by Alexander Binshtok et al. PNAS
Abstract
The analgesic paracetamol metabolite AM404 acts peripherally to directly inhibit sodium channels
Paracetamol has long been the go-to painkiller for mild-to-moderate pain management. Its analgesic effect is primarily attributed to its metabolite AM404, which is believed to act on cannabinoid receptors or TRPV1 channels in central nervous system neurons.
Here, we reveal that AM404 is produced by primary sensory neurons. It inhibits the sodium current in pain-sensing nerve cells, curbing action potential (AP) generation and thereby reducing nociceptive behavior in rats.
We demonstrated that this analgesic effect of AM404 is mediated by its direct inhibition of nociceptive voltage-gated sodium channels (Na1.8 and Na1.7) via the local anesthetic binding site. This inhibition was specific to AM404 and not observed with other paracetamol metabolites.
Our findings suggest that the analgesic effect of paracetamol is primarily mediated by direct AM404-induced inhibition of nociceptive sodium channels at the peripheral nociceptor neurons. This paves the way for the potential development of AM404 as a selective local analgesic.
Take note of this captivating research that reveals paracetamol's untold story, opening exciting new possibilities for pain management.
- The groundbreaking mechanism uncovered by researchers at the Hebrew University of Jerusalem shows that the common painkiller paracetamol works not only in the brain but also at the peripheral nerves, challenging long-held beliefs.
- This revolutionary discovery, published in PNAS, highlights the production of a compound named AM404 by the body after a dose of paracetamol, which blocks sodium channels responsible for transmitting pain within pain-sensing nerve endings.
- The researchers suggest that the analgesic effect of paracetamol is primarily mediated by direct AM404-induced inhibition of nociceptive sodium channels at the peripheral nociceptor neurons, opening the door for the potential development of AM404 as a selective local analgesic for pain management.
