Location may be key to effectively controlling pain

Terence Coderre

Terence Coderre

Targeting the pain receptor at the cell’s nucleus has a major effect on its ability to transmit pain signals.

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 by 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,  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.

Coderre’s team 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.

Funding for this research comes from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (NIH), grant number NS081454. Additional funding comes from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, a fellowship from the Canadian Institutes of Health Strategic Training Program in Pain: Molecules to Community, and the Louise and Alan Edwards Foundation, In addition, the drug used in the experiments, LY393053 was donated by Eli Lilly and Co.

Source of text: McGill University

Original research article:

Intracellular mGluR5 plays a critical role in neuropathic pain,  Vincent K, Cornea VM, Jong YI, Laferriere A, Kumar N, Mickeviciute A, Fung JST, Bandegi P, Ribeiro-da-Silva A, O’Malley KL, Coderre TJ. Nature Communications, 10.1038/NCOMMS10604 (Open access)