Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecule discovered to be key to pain sensitivity

24.10.2006
Gene variation identifies those with higher pain threshold, lower risk of chronic pain

Sensitivity to pain and the risk of developing chronic pain appear to be influenced by levels of a molecule known to be required for the production of major neurotransmitters. In the November issue of Nature Medicine, an international research team based at Massachusetts General Hospital (MGH) describes this unexpected role for the molecule called BH4 and their findings that a particular set of variations in a human gene involved in synthesizing the molecule appears to reduce pain sensitivity.

"This is the first evidence of a genetic contribution to the risk of developing neuropathic pain in humans. The pain-protective gene sequence, which is carried by about 20 to 25 percent of the population, appears to be a marker both for less pain sensitivity and a reduced risk for chronic pain," says senior author Clifford Woolf, MD, PhD, director of the Neural Plasticity Research Group in the MGH Department of Anesthesia and Critical Care. "Identifying those at greater risk of developing chronic pain in response to medical procedures, trauma or diseases could lead to new preventive strategies and potential treatments."

Previous studies in animals have shown that specific strains or related groups of rodents have significant differences in their risk of developing either neuropathic pain, which results from nerve damage, or inflammatory pain, associated with the immune system's response to injuries or conditions like arthritis. But except for some rare inherited conditions, there has been no evidence that genetics contributed to the risk of neuropathic pain in humans.

The research team had previously used gene chips to find that nerve damage in rats altered the regulation of several hundred genes in associated nerve cells. They began the current study by searching through these genes to find any associated with common metabolic pathways and found that three genes that increased expression in response to nerve damage encoded enzymes involved in the production and recycling of BH4, which is essential for the production of serotonin, dopamine, norepinephrine and nitric oxide. Tests in rat models found that the BH4-synthesizing enzymes were activated in injured sensory neurons and that substances known to inhibit those enzymes reduced pain, acting as analgesics. Directly injecting BH4 or a similar molecule increased the animal's response to several painful stimuli.

As a result of the animal studies, the researchers hypothesized that particular variations of human genes involved in the regulation of BH4 might be associated with different responses to pain. Searching for alterations in the gene for GCH1, the human version of the key BH4-controlling enzyme, they genotyped tissues from 168 patients who had participated in an earlier study of spinal disk surgery. One specific GCH1 haplotype - a set of variations in the gene that are inherited together - was more common in study participants who reported less neuropathic pain in the year after their surgery.

To see if that haplotype had a similar association with other types of pain, the researchers studied almost 400 healthy volunteers, who participated in tests of their response to various slightly painful experimental stimuli. Again, those participants with the protective GCH1 haplotype - which the investigators showed reduces the production of BH4 - also reported less pain, and volunteers with two copies of the protective sequence were even less sensitive to pain.

"Our results tell us that BH4 is a key pain-producing molecule – when it goes up, patients experience pain, and if it is not elevated, they will have less pain," says Woolf. "The data also suggest that individuals who say they feel less pain are not just stoics but genuinely have inherited a molecular machinery that reduces their perception of pain. This difference results not from personality or culture, but real differences in the biology of the sensory nervous system.

"Now we need to identify what regulates the switching on of BH4-controlling enzymes after nerve injury and how BH4 alters the excitability of pain fibers. We also would like to see whether those with the protective haplotype might participate more frequently in potentially painful activities – such as extreme sports – or if they have reduced levels of pain in arthritis and other common conditions," he adds. Woolf is the Richard Kitz Professor of Anaesthesia Research at Harvard Medical School.

Sue McGreevey | EurekAlert!
Further information:
http://www.mgh.harvard.edu/

Further reports about: BH4 Chronic Variation developing haplotype neuropathic pain sensitivity

More articles from Life Sciences:

nachricht Cnidarians remotely control bacteria
21.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Immune cells may heal bleeding brain after strokes
21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

Cnidarians remotely control bacteria

21.09.2017 | Life Sciences

Monitoring the heart's mitochondria to predict cardiac arrest?

21.09.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>