Naturally occurring protein has a role in chronic pain

June 12, 2012

Researchers in France and Sweden have discovered how one of the body's own proteins is involved in generating chronic pain in rats. The results, which also suggest therapeutic interventions to alleviate long-lasting pain, are reported in The EMBO Journal.

Chronic pain is persistent and often difficult to treat. It is due, at least in part, to changes in molecular signalling events that take place in neurons, alterations that can ultimately disrupt the transmission of from the spinal cord to the brain.

"We are fortunate to have a wide range of technologies that allow us to look more precisely at the molecular events that lead to the onset of chronic pain in animals," said Marc Landry, lead author of the study and Professor at the University of Bordeaux. "Our results show that the levels of the naturally occurring protein 14-3-3 zeta are higher in the spinal cord of rats that have chronic pain. Moreover, we have been able to demonstrate how 14-3-3 zeta triggers changes in the signalling pathway that leads to the symptoms of chronic pain."

The 14-3-3 zeta protein disrupts the interaction between the two subunits of the GABAB receptor, a protein complex found on the surface of . GABAB receptors are G-protein coupled receptors, a family of receptors that regulate many and which are frequently targeted for drug development.

The researchers used antibody labelling and microscopy techniques to investigate the of the signalling proteins. In cells and living animals, they were able to show that the 14-3-3 zeta protein interacts directly with the B1 subunit of the GABAB receptor. This interaction impairs the effective signalling of the receptor and limits the pain-relieving effects of the GABAB receptor under conditions of chronic pain.

The researchers also showed that the treatment of rats with a specific (siRNA) or a competing peptide, molecules that interfere with the action of the 14-3-3 zeta protein, inhibited chronic pain.

"The impairment of the GABAB receptor by 14-3-3 zeta is a novel mechanism for the modulation of chronic pain," said Landry. "We see potential in combining the use of inhibitors that interfere with the action of 14-3-3 zeta together with existing drug treatments like Baclofen for chronic pain. Targeting the GABAB dissociation process may be of therapeutic interest since it may allow classical pain killers to be more effective."

Explore further: The protein that makes us remember pain

More information: Impairment of GABAB receptor dimer by endogenous 14-3-3 zeta in chronic pain conditions, Sophie Laffray, Rabia Bouali-Benazzouz, Marie-Amélie Papon, Alexandre Favereaux, Yang Jiang, Tina Holm, Corentin Spriet, Pascal Desbarats, Pascal Fossat, Yves Le Feuvre, Marion Decossas, Laurent Héliot, Ulo Langel, Frédéric Nagy, Marc Landry, The EMBO Journal, doi:10.1038/emboj.2012.161

Related Stories

The protein that makes us remember pain

May 13, 2011
(PhysOrg.com) -- New research by scientists in Arizona in the US has demonstrated that an enzyme makes the body remember and remain sensitive to pain after an injury has healed.

New insight into pain mechanisms

April 25, 2012
(Medical Xpress) -- Researchers in the UCL Wolfson Institute for Biomedical Research have made a discovery which could help the development of analgesic drugs able to treat nerve damage-related pain.

Recommended for you

Scientists find key to regenerating blood vessels

November 23, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The ...

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 ...

0 comments

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.