New Drugs To Be Targeted At Pain Receptors Deep In The Nerve Cell

Today's post from sciencedaily.com (see link below) may at first sight seem a little difficult to understand but basically, when the body experiences pain, there are pain receptors on the surface of nerve cells that identify it and transmit the information further and let you feel that pain. If the pain is extreme, sometimes these pain receptors retreat to the nucleus of the cell, as if it's 'safer' there. Pain relieving drugs are designed to block the pain signals in the receptors at the surface of the cell but if the receptors have migrated to the nucleus then the drugs don't have any effect. This knowledge enables researchers to design pain-relieving drugs that can penetrate the nerve cell to the nucleus and thus block the signals from reaching the receptors. They can then 'safely' return to the surface of the cell. At least that's the theory and although it may seem like double-dutch to most of us, sometimes it's interesting to know in which direction the scientists are going.
 

Location may be key to effectively controlling pain
Date:February 3, 2016 Source:McGill University
 
In real estate, location is key. It now seems the same concept holds true when it comes to stopping pain. New research published in Nature Communications indicates that the location of receptors that transmit pain signals is important in how big or small a pain signal will be -- and therefore how effectively drugs can block those signals.

Blocking pain receptors in the nucleus of spinal nerve cells could more effectively control pain than interfering with the same type of receptors located on cell surfaces. The scientists also found that when spinal nerve cells encounter a painful stimulus, some of the receptors will migrate from the cell surface into the nucleus.

A team of researchers led by McGill University's Director of Anesthesia Research Terence Coderre and Karen O'Malley at Washington University in St. Louis, found that rats treated with investigational drugs to block the activity of the receptors in the nucleus soon began behaving in ways that led them to believe the animals had gotten relief from neuropathic pain. According to Prof. Coderre, "drugs that penetrate the spinal nerve cells to block receptors at the nucleus were effective at relieving pain, while those that don't penetrate the nerve cells were not. Rats with nerve injuries had less spontaneous pain and less pain hypersensitivity after blocking receptors at the nucleus, while the pain sensitivity of normal rats was not affected."

Location is key
Scientists have been studying glutamate receptors in the pain pathway for decades. What's new, Coderre explained, is that these most recent experiments -- in cell cultures and rats -- demonstrate that the location of the receptor in the cell has a major effect on the cell's ability to transmit pain signals.

The researchers focused mainly on nerve cells in the spinal cord, an important area for transmitting pain signals coming from all parts of the body.

"We'll now focus our research at determining what events cause the glutamate receptors to migrate to the nucleus, and how to produce drugs that more specifically block glutamate receptors only at the nucleus," added Coderre.

Story Source:

The above post is reprinted from materials provided by McGill University. The original item was written by Cynthia Lee. Note: Materials may be edited for content and length.

Journal Reference:
Kathleen Vincent, Virginia M. Cornea, Yuh-Jiin I. Jong, André Laferrière, Naresh Kumar, Aiste Mickeviciute, Jollee S. T. Fung, Pouya Bandegi, Alfredo Ribeiro-da-Silva, Karen L. O’Malley, Terence J. Coderre. Intracellular mGluR5 plays a critical role in neuropathic pain. Nature Communications, 2016; 7: 10604 DOI: 10.1038/NCOMMS10604

http://www.sciencedaily.com/releases/2016/02/160203111018.htm