As most readers are aware, painonline is the communications wing of the Wall/McHenry database. (Patrick Wall/Kenneth McHenry). Dr. Wall’s fame increases even after his death. He was a kind man and a worthy hero, and also happened to be right about so much which he theorized.
More than fifteen years ago, Dr. Patrick Wall, already famous for his “gate theory” of pain with Ron Melzack of Montreal was making the statement, “Peripheral injury induces Central Change”. What did this mean? Dr. Wall was convinced that central pain patients would not be capable of enhanced or evoked pain unless peripheral injury had the power to influence something fundamental in the central nervous system, It was the notion of a cascade effect. It was of course theoretical on Dr. Wall’s part. Dr. Wall also believed that pain was the expression of mismatching between a normal “template” of signal innate within the brain compared to what was actually coming up via the thalamus. This is the last major theory of Wall to be proved, but it will likely be confirmed eventually.
Now, however, his theory on peripheral contribution to central disorders has been borne out. The information comes from the legendary group of pain researchers centered in Toronto, the legacy of Ron Tasker’s work on central pain in the 50’s.
Writing in Brain Behav Immun. 2006 Dec 16 in an article entitled, “Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury” Simon Beggs* and Michael Salter** have hit major paydirt.
Glia are cells which surround nerve cells in the central nervous system. Although they are NOT neurons, their function is so intimately related to neurons that it is proper to speak of them as nerve cells, although at various times they have been referred to as immune response cells or support cells.
It has been known for several years that the glia which surround neurons supply the growth factors which stimulate production of pain chemicals by themselves and by the neurons. It has recently been proven that glia modulate neuronal excitability. What was NOT known and what these two scientists have now shown is that the glia actually INCREASE in number in response to nerve injury. There is a QUANTITATIVE response to neuropathic pain. The response is in the NUMBER of glia!
Just how powerful is this response. According to this study, the number of glia in the dorsal horn of the cord receiving area for the sciatic nerve, which receives sural input, went from an average number of 28,591+/-2715 to 82,034+/-8828 following the creation of neuropathic pain. This ia a QUADRUPLING of cells, of the glia which activate neurons. We have queried before just how much increase in sensitivity in the nerves would be necessary to create the combined power of central pain burning dysesthesia. There are some suggestions that even a mere doubling of nerve sensitivity would translate logarithmically into many times over in the ultimate pain signal at the thalamus. Here we have a study of injury in part of a single nerve which results in quadrupling of glia in the receptive area of the dorsal horn. Because MANY neurons make up a nerve, the combined effect is multipled many times over. Perhaps we should stop calling it hypersensitization and call it HYPERsensitization.
That is certainly what the burning feels like. It is time for the doubting Thomases in the pain world to admit they were wrong, entirely wrong about catastrophizing and to start admitting that nerve injury pain can be really serious. It is a problem that merits a solution, that requires tackling for the sake of the human beings who must endure it. And if peripheral nerve injury can cause this kind of response, imagine the magnitude of the problem when the cord itself or the brain are injured and the microglia start their work of agony at the heart of the nervous sytem.
The authors repeated the experiment many times, and found that their method was accurate spatially and quantitatively. It was a reproducible assay of nerve injury pain. It is easy enough to sacrifice part of a peripheral nerve to make a point. What do we have to sacrifice to convince those funding research that those with central pain are in desperate need of help.
Rooney et al in Dec 2006 Exp. Neurology showed that preemptive use of lidocaine helped prevent nerve injury pain after back surgery. It is clear that something has the potential to occur around the time of injury which can be blocked. It may be that in the future, effective blocking of ion channels around the area of nerve injury may prevent the subsequent development of central pain. If so, isn’t it high time we found out. We already have enough poor souls in agony from central pain and other nerve injury. Why not get serious and stop this tragedy.
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We have already cited important works from these authors, who are associated with Jeffrey Coull, who has written for us here at painonline. The work coming from the University of Toronto Hospital for Sick Children is the greatest of its kind in the entire world. Simon Beggs and associates’ book on Microglia published by Springer Verlag is a masterpiece and Beggs and Salter’s work on the anion shift in neuropathic pain is probably the most significant information ever to be published on why pain inhibition fails in neuropathic pain. They are also the ones who discovered BDNF at the heart of glial activation in nerve injury. They may be the only people in the world smart enough to really understand how important their own work is. We have many hopes pinned on the ventures of this group of pain geniuses, (and they look so young!) Hail Canada!
