The protein that makes us remember pain
(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.
Research in 2006 by Professor Todd C. Sacktor of the State University of New York Downstate Medical Center found that the protein kinase M zeta (PKMzeta) appears at the synapses (gaps between neurons) and must be continually recreated at the synapses. If it disappears, so do memories of the pain. Sacktors team were able to irreversibly erase memories of pain in rats by using a chemical called zeta-inhibiting peptide (ZIP) which inhibits PKMzeta. In later research the showed that extra PKMzeta affected the brains of rats by boosting old memories.
Now new research by Marina Asiedu and Dipti Tillu and colleagues from the University of Arizona Medical School has shown that PKMzeta is also responsible for the lingering pain and sensitivity felt after an injury. The researchers knew that when pain is experienced the neurons carrying the pain signals develop stronger connections, especially in the dorsal horn section of the spinal cord. The same thing happens in the brain when we learn something new, and so they decided to test the hypothesis that PKMzeta is involved in both processes.
The team injected mice in the paw with Interleukin-6 (IL-6), a protein that produces mild swelling and makes the paw more sensitive for up to three days. They later injected prostaglandin E2 (PGE2) into the paw, and the mice reacted to the chemical, but only if they had previously been injected with IL-6. If the mice were injected with ZIP at the same time as IL-6 or up to three days afterwards, their paws never became more sensitive to PGE2, indicating they had not developed a memory for the pain. When they injected a protein that mimics PKMzeta, the sensitivity returned.
Researchers in Korea made similar discoveries for chronic pain in research published in 2010. Dr Xiang-Yao Li and colleagues found that PKMzeta creates memories in chronic pain caused by nerve damage, and in this research they found the protein affects the anterior cingulated cortex (ACC) part of the brain. An injection of ZIP was found to ease the pain, but only for a few hours and not permanently.
If the protein kinase M zeta produces the same effects in humans, new treatments could be developed that target PKMzeta to treat severe or chronic pain, and conditions such as central neuropathic pain syndrome, in which people retain the memory of a pain long after the injury has healed. PKMzeta may also play a role in other conditions such as addictions and post traumatic stress disorder.
More information: Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization, The Journal of Neuroscience, 4 May 2011, 31(18): 6646-6653; doi:10.1523/JNEUROSCI.6286-10.2011
Sensitization of the pain pathway is believed to promote clinical pain disorders. We hypothesized that the persistence of a sensitized state in the spinal dorsal horn might depend on the activity of protein kinase M ζ (PKMζ), an essential mechanism of late long-term potentiation (LTP). To test this hypothesis, we used intraplantar injections of interleukin-6 (IL-6) in mice to elicit a transient allodynic state that endured ∼3 d. After the resolution of IL-6-induced allodynia, a subsequent intraplantar injection of prostaglandin E2 (PGE2) or intrathecal injection of the metabotropic glutamate receptor 1/5 (mGluR1/5) agonist DHPG (dihydroxyphenylglycol) precipitated allodynia and/or nocifensive responses. Intraplantar injection of IL-6 followed immediately by intrathecal injection of a PKMζ inhibitor prevented the expression of subsequent PGE2-induced allodynia. Inhibitors of protein translation were effective in preventing PGE2-induced allodynia when given immediately after IL-6, but not after the initial allodynia had resolved. In contrast, spinal PKMζ inhibition completely abolished both prolonged allodynia to hindpaw PGE2 and enhanced nocifensive behaviors evoked by intrathecal mGluR1/5 agonist injection after the resolution of IL-6-induced allodynia. Moreover, spinal PKMζ inhibition prevented the enhanced response to subsequent stimuli following resolution of hypersensitivity induced by plantar incision. The present findings demonstrate that the spinal cord encodes an engram for persistent nociceptive sensitization that is analogous to molecular mechanisms of late LTP and suggest that spinally directed PKMζ inhibitors may offer therapeutic benefit for injury-induced pain states.
© 2010 PhysOrg.com
- Novel approach to chronic pain relief Dec 02, 2010 | not rated yet | 0
- Enzyme enhances, erases long-term memories in rats Mar 04, 2011 | not rated yet | 0
- Switch off enzyme to control chronic pain, say researchers Jan 12, 2011 | not rated yet | 0
- Protein found that may provide relief from neuropathic pain Dec 05, 2007 | not rated yet | 0
- A step forward in targeted pain therapy Jan 22, 2008 | 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
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...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
Neuroscience May 18, 2013 | 5 / 5 (1) | 0 |
The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...
Neuroscience May 17, 2013 | 4 / 5 (1) | 0 |
(Medical Xpress)—What if the quality of your work depends more on your focus on the piano keys or canvas or laptop than your musical or painting or computing skills? If target users can be convinced, they ...
Neuroscience May 17, 2013 | 3.7 / 5 (3) | 0 |
Neurological disorders can have a devastating impact on the lives of sufferers and their families.
Neuroscience May 17, 2013 | 5 / 5 (1) | 0 |
If you're a left-brain thinker, chances are you use your right hand to hold your cell phone up to your right ear, according to a newly published study from Henry Ford Hospital in Detroit.
Neuroscience May 16, 2013 | 2 / 5 (2) | 0 |
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
13 hours ago | 4.8 / 5 (5) | 0 |
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
13 hours ago | 5 / 5 (3) | 0 |
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
12 hours ago | 5 / 5 (1) | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
12 hours ago | 5 / 5 (2) | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
16 hours ago | not rated yet | 0
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
12 hours ago | 5 / 5 (1) | 0