New Target For Pain Relief Found
By Ed Edelson
HealthDay Reporter
THURSDAY, May 6 (HealthDayNews) -- German researchers report the discovery of a key link in the molecular pathway that sends pain-generating signals to the brain.
The finding could open the way to a new generation of more effective painkillers, said Ulrike Mller, a neurobiologist at the Max-Planck-Institute for Brain Research in Frankfurt and a member of the team reporting the discovery in the May 7 issue of Science.
The molecule they describe is a receptor that sits on the surface of cells in the spinal cord. The function of that receptor, designated GlyR alpha3, is to block transmission of pain signals generated by injury or inflammation, Mller explained.
But GlyR alpha3 activity is blocked by prostaglandins, molecules that are produced by pain-causing activity, she said.
http://www.forbes.com/lifestyle/health/feeds/hscout/2004/05/06/hscout518772.html
dejerine
05-07-2004, 09:48 AM
Max, thanks for pointing out the article. I don't know whether it is the same Ulrike Muller but equally interesting article in May 5 J. Neuroscience on Memory.
It has long been known that people with Central Pain have memory problems, but clinicians tend to keep forgetting this.
It is hard to describe but the liteature terms this a loss in "working memory". It is sort of like a loss of K in your computer. When pressed most CP people with burning pain (ST tract) will recognize this is present, but may NOT have associated it with CP. Those will only lancinating pain (posterior columns) do not usually report loss of working memory, perhaps because their pain, although severe, is intermittent.
At any rate, in Muller's article they prove there are three phases in memory. Roughly stated they break the phases of memory into intermediate, medium term, and long term memory. What makes this interesting is that memory is determined by our old friend, Protein Kinase A.
You will remember that knockout rats who lack either Protein Kinase C (see Wise's post) OR Protein Kinase A CANNOT be made to acquire Central Pain. The article in Science a few years ago showed that when a cell toxin is tied to Protein Kinase C (PKC) the rats whose PKC receptor cells are ablated lose memory. So Wise was wise to comment on PKC. Muller's article shows that rats fed sucrose 4 hours before conditioning are impaired in memory because of actions on Protein Kinase A.
Thus, we finally see a link at some level between the molecular requirements for memory and the molecular role of protein kinases in Central Pian. Do not run this past your doctor, as he is unlikely to know of the link between PKA and CP, and most certainly will not know of the common working memory loss in CP. We live with this daily, but it is a little credited aspect of the difficulty of dealing with CP.
Not to worry, however, as the excellent memory of behaviorists fixates their mind on all those soldiers who have their limbs blown off with no pain, so that they are unable to get real and understand that long term pain people like us cannot maintain any such feat, and in fact, are dying of pain before their eyes, as they dreamily remind us of the fortitude of amputee soldiers.
We can hardly find an amputee soldier who experienced no pain. We keep running into the insignificant minority whose pain hurt like he__. I have broken bones, etc. but the pain did not match CP. AND, it stopped.
I questioned one behaviorist about this and he admitted he had never actually met a painless soldier, but he had HEARD so much about it, it must be so.
He opined that moderate pains probably cannot be surpressed, but that really terrible pain probably does not occur because the brain eliminates it. He was unable to provide any anatomic, neurophysiologic, or experiential basis for his opinion, but he said it must be so, or why else did soldiers feel no pain. I replied this was somewhat circular. He said, "Only a fool would question it. I do not know any painless soldiers, but they must exist or else why all the reports by behavioral scientists", walking this flat earth.
I took a brief jaunt through the VA hospital and I guess the painless soldiers had been sent to some other hospital, since these men had pain stories to tell. I asked them about the theory that severe pain is painless, while moderate pain is not, but they looked at me like I was crazy. That would explain my terrible burning.
I had severe pain during two of my surgeries, but thanks to the anesthesia I don't remember it. So, the brave soldiers may have had the pain but something blocked it out. I wonder how LONG that "something" is active. Twenty years, with constant glutamate/NMDA bombardment?? That is a long time.
CP is constant. I am looking for the soldier who has one limb blown and then another, at time intervals, to ask him if the fourth one was also painless. Back to the VA. They love requests from "scientists" who know pain is a myth, and only "nonpain" is credible.
And, oh yes, since skeptics wimp out, when given capsaicin, we can only conclude the pain is moderate, and not severe.
[This message was edited by dejerine on 05-07-04 at 03:32 PM.]
[This message was edited by dejerine on 05-07-04 at 03:40 PM.]