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: A step forward in targeted pain therapy

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

A step forward in targeted pain therapy

January 22, 2008

Our bodies sense painful stimuli through certain receptors located in the skin, in joints and many internal organs. Specialized nerve fibers relay these signals coming from the periphery to the brain, where pain becomes conscious. ...

Researchers find relief for chronic pain

January 22, 2008

Researchers in the Department of Medicine and Department of Neurosciences at Mount Sinai School of Medicine have discovered that chronic pain can be successfully treated with novel targeted gene therapy. In an effort to find ...

Novel approach to chronic pain relief

December 2, 2010

(PhysOrg.com) -- An international team of scientists have found what they believe could be a novel approach to more effective, targeted relief of chronic pain caused by nerve injuries. The research, a collaboration involving ...

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

New method creates endless supply of kidney precursor cells

August 25, 2016

Salk Institute scientists have discovered the holy grail of endless youthfulness—at least when it comes to one type of human kidney precursor cell. Previous attempts to maintain cultures of the so-called nephron progenitor ...

Strict diet combats rare progeria aging disorders

August 25, 2016

Mice with a severe aging disease live three times longer if they eat thirty percent less. Moreover, they age much healthier than mice that eat as much as they want. These are findings of a joint study being published today ...

New avenue for understanding cause of common diseases

August 25, 2016

A ground-breaking Auckland study could lead to discoveries about many common diseases such as diabetes, cancer and dementia. The new finding could also illuminate the broader role of the enigmatic mitochondria in human development.

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.