The sensation of cold is shut down by inflammation

July 2, 2012
The analgesic effects of cooling or menthol are disrupted by inflammation, but scientists have not been clear how inflammation interferes with cold perception, until now. Credit: Dept. Pharmacology, University of Cambridge.

(Medical Xpress) -- Research groups at the University of Cambridge and the Instituto de Neurociencias, in Spain, have discovered a new and unexpected mechanism by which cold sensation is regulated, and opens up the possibility of developing drugs to mimic the well-known analgesic effects of cold and menthol.

The sensation of coolness is essential for our everyday life. Although extreme cold causes pain, moderate cooling inhibits pain, such as holding a burned hand under a cold tap. Another way to produce a sensation of coolness, and therefore to relieve pain, is to apply menthol, a compound present naturally in mint and widely used in peppermints, mentholated cigarettes and in pain-relieving rubs.

Cooling works by activating a named TRPM8, an which allows electric charge to flow across cell membranes. Menthol produces a sensation of coolness by acting on the same protein.

Unfortunately, the analgesic effects of cooling or menthol are disrupted by inflammation, but to date scientists have not been clear how inflammation interferes with cold .

Dr. Xuming Zhang and Professor Peter McNaughton at the Department of Pharmacology, University of Cambridge, have found that a novel mechanism is responsible – a critical intermediate protein, called a Gq protein, binds directly to TRPM8 and when compounds, such as histamine, are released by inflammation, Gq is rapidly activated and switches TRPM8 off. Cold sensation is therefore deactivated by . The findings suggest that reversing this process, and reactivating cold sensation, may be a useful analgesic strategy.

“This novel mechanism opens up the possibility that the cold pathway could be manipulated clinically simply by disrupting the interaction of Gq protein with the TRPM8 channel” Dr. Zhang said.

The finding that Gq directly inhibits TRPM8 is surprising because while Gq is involved in several cellular signalling process, it has not previously been thought to act on ion channels in this way.

The research is published today in the journal Nature Cell Biology.

Explore further: Researchers discover way to block body's response to cold

Related Stories

Researchers discover way to block body's response to cold

March 1, 2012
Researchers at St. Joseph's Hospital and Medical Center in Phoenix, Arizona, in collaboration with Amgen Inc. and several academic institutions, have discovered a way to block the body's response to cold using a drug. This ...

Chronic pain gene identified

September 8, 2011
British researchers say they have identified the gene that controls chronic pain, opening the door to new drug therapies that block the chemical processes that cause chronic back pain, headaches or arthritis.

Recommended for you

Researchers find infectious prions in Creutzfeldt-Jakob disease patient skin

November 22, 2017
Creutzfeldt-Jakob disease (CJD)—the human equivalent of mad cow disease—is caused by rogue, misfolded protein aggregates termed prions, which are infectious and cause fatal damages in the patient's brain. CJD patients ...

Surprising roles for muscle in tissue regeneration, study finds

November 22, 2017
A team of researchers at Whitehead has illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration. In a paper published in the November 22 issue of Nature, they ...

Study reveals new mechanisms of cell death in neurodegenerative disorders

November 22, 2017
Researchers at King's College London have discovered new mechanisms of cell death, which may be involved in debilitating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

Researchers discover key signaling protein for muscle growth

November 20, 2017
Researchers at the University of Louisville have discovered the importance of a well-known protein, myeloid differentiation primary response gene 88 (MyD88), in the development and regeneration of muscles. Ashok Kumar, Ph.D., ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

JGHunter
not rated yet Jul 02, 2012
Presumably this works the other way, as an explanation as to why swollen and painful areas feel "warm", because this process isn't happening... The article states this protein is activated by menthol, does this protein, TRPM8, get activated in painful areas automatically by the body in the same way that adrenaline is released after an injury? Or is it something we have to do manually?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.