Posted on Jul 06, 2018, 10 p.m.
A non-opioid investigational drug has been found to inhibit macrophage receptor on immune cells which may relieve pain particularly in cases with chronic neuropathic pain conditions such as diabetic neuropathy, as published in The Journal of Neuroscience.
In an effort to address the opioid addiction epidemic researchers having been working to find alternative strategies to treat pain, focused on nerve cells that transmit pain signals to the brain and spinal cord. New research shows that targeting receptors on immune cells may be more effective especially in the case of chronic pain.
EMA401 non-opioid investigational drug has been showing great promise as treatment for lingering nerve pain following shingles infection. Investigating how the drug helped control pain it was found by researchers from the University of Washington that it did not hit nerve cells, rather it targeted a receptor on immune cells.
Angiotensin II type 2 receptor was inhibited by EMA401 that is targeted by medications which lower blood pressure. It was thought to work by interacting with the receptor on nerve cells, with closer inspection that theory was proven wrong. Nerve cells from mice in culture dishes added with the angiotensin hormone had no reactions, there wasn’t a receptor on sensory neurons meaning signals could not be transmitted, adding macrophages to the dish provided transmitting of pain signals. Angiotensin injections into mice indicated they felt pain and withdrew paws when touched; reducing the numbers of macrophages in mice showed the animals to appear not to feel pain in response to the injections but as macrophages repopulated the response to pain returned. Increased macrophages numbers were found along with degenerative nerve fibers in skin biopsies from patients with diabetic neuropathy which supports these observations.
Increasing potential targets available for painkillers including receptors on immune cells may make it possible to develop more effective medications with fewer side effects. EMA401 unlike opioids does not cross blood brain barriers, eliminating numerous side effects which includes addiction and potential for abuse. Widening potential targets to include macrophages may make it possible to develop therapies for chronic pain.
Materials provided by Washington University School of Medicine.
Note: Content may be edited for style and length.
Andrew J. Shepherd, Bryan A. Copits, Aaron D. Mickle, Páll Karlsson, Suraj Kadunganattil, Simon Haroutounian, Satya M. Tadinada, Annette D. de Kloet, Manouela V. Valtcheva, Lisa A. McIlvried, Tayler D. Sheahan, Sanjay Jain, Pradipta R. Ray, Yuriy M. Usachev, Gregory Dussor, Eric G. Krause, Theodore J. Price, Robert W. Gereau, Durga P. Mohapatra. Angiotensin II triggers peripheral macrophage-to-sensory neuron redox crosstalk to elicit pain. The Journal of Neuroscience, 2018; 3542-17 DOI: 10.1523/JNEUROSCI.3542-17.2018