New insights into the synaptic basis of chronic pain
A team of scientists has found a novel road-block in the pain pathway, which could be used to treat chronic pain. Their results are published March 13 in the online, open-access journal PLoS Biology.
Pain is an important physiological function that protects our bodies from harm. Pain-sensing nerves transduce harmful stimuli into electrical signals and transmit this information to the brain via the spinal cord. However, when these nerves get activated persistently, such as after injury or inflammation, the information flow into the spinal cord is remarkably amplified. This phenomenon, termed 'synaptic long-term potentiation (LTP)', is an important biological property that is evolutionarily conserved from lower organisms to humans.
To gain a better understanding of how LTP works in the context of pain signaling, the team led by Rohini Kuner (Heidelberg University, Germany) and Ceng Luo (Fourth Military Medical University, China) took advantage of biochemical, genetic, physiological, and behavioral tools available in mice. They studied how LTP works at the synaptic connection between peripheral pain sensors and spinal cord neurons. They found that presynaptic events that unfold in the spinal endings of pain-sensing nerves are required for this pain amplification.
"Our results indicate that an enzyme termed cGMP-activated Kinase 1 (PKG-I) is a key player in this important process", says Ceng Luo. By removing PKG-1 specifically from the presynaptic neurons in this pathway, their group found that not only was LTP abolished, but that pain-related memory and behavior were also altered. Can these basic biological findings be put to use? Chronic pain is a major cause of poor quality of life worldwide; recent demographic studies indicate that one in every six people in Europe suffers from chronic pain.
"Our observation that genetically silencing PKG-I, or blocking its activation, in pain-sensing nerves markedly reduced chronic inflammatory pain paves the way for potential new therapeutic approaches,'' says Rohini Kuner.
More information: Luo C, Gangadharan V, Bali KK, Xie R-G, Agarwal N, et al. (2012) Presynaptically Localized Cyclic GMP-Dependent Protein Kinase 1 Is a Key Determinant of Spinal Synaptic Potentiation and Pain Hypersensitivity. PLoS Biol 10(3): e1001283. doi:10.1371/journal.pbio.1001283
Provided by Public Library of Science
- Researchers find possible breakthrough to relieve pain following spinal cord injury Nov 30, 2011 | not rated yet | 0
- Switch off enzyme to control chronic pain, say researchers Jan 12, 2011 | not rated yet | 0
- Ouch! Abrupt opioid withdrawal increases pain sensitivity Jul 10, 2009 | not rated yet | 0
- Opioids erase memory traces of pain Jan 16, 2012 | not rated yet | 0
- Protein found that may provide relief from neuropathic pain Dec 05, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research 17 hours ago | not rated yet | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research 17 hours ago | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research 18 hours ago | not rated yet | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research 18 hours ago | 5 / 5 (2) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research 20 hours ago | 5 / 5 (2) | 0
(Medical Xpress)—The way Alzheimer's disease is portrayed by advocacy groups and the media is having undue influence on the euthanasia debate, according to a Deakin University nursing ethics professor.
51 minutes ago | not rated yet | 0
(Medical Xpress)—Patients with diabetes who are depressed are much more likely to develop episodes of dangerously low blood sugars, or hypoglycemia, than are those who are not depressed, a new study has ...
46 minutes ago | not rated yet | 0 |
(Medical Xpress)—UCD researchers led by Conway Fellow, Professor David Brayden in UCD School of Veterinary Medicine have successfully reduced inflammation in the swollen arthritic knees of a murine model using a novel nanoparticle.
1 minute ago | not rated yet | 0
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
21 minutes ago | not rated yet | 0
Can human genes be patented? That was the question posed by Alan J. Snyder, vice president and associate provost for research and graduate studies at Lehigh, and Lee Kaplan, scientific director of cellular and molecular genetics ...
1 hour ago | 4 / 5 (1) | 0
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
11 minutes ago | not rated yet | 0