House has been our favorite TV show for some time. The reason is that Dr. Gregory House deals in medical truth. He does this both in the way he behaves and in the way he works up patients. For example, House is addicted to opiates, due to nerve injury in his leg.

Basically he reminds us that pain hurts, and that those who have it are not more stupid, nor weaker than those not in pain. “If you have a buttload of pain, you need a buttload of pills.” This politically incorrect and medically incorrect statement is nevertheless humanly correct. If someone were to insist House give them an analog scale of 1-10 on his pain, House would do something to actually give them pain, so they stop asking him questions which cannot be answered.

The analog scale is supposed to be about pain. However, what it really is about is INTENSITY. Pain intensity is, unfortunately, on;y ONE aspect of pain. If you carry a sack of groceries two blocks, they are not so heavy. If you have to carry them across the plains, they are VERY heavy. Those manageable groceries of two blocks will make your arms fall off somewhere around Omaha.

Central Pain is the worst pain state known to man because it is severe AND because it lasts. There is nothing which covers that on the oxymoronic, paradoxical, but impressive sounding, “digital analog scale”.  Translation: Someone has been playing you for the fool.

As every medical student not roped onto the Procrustean analog scale bed knows, pain must be evaluated as to quality, similarity to prior pain, exacerbations and relieving aspects, duration, intermittency, radiation, and location. All of these very important aspects are conveniently ignored in the 1-10 system. Consequently, the examiner risks remaining completely ignorant of central pain.

Because of this, medical science is leaning toward abolishing the term, “central pain”, which has unique clinical manifestations, and lumping it under the much less specific term, “neuropathic pain”.

If only we could summon Dr. House to put these befuddled, hurried clinicians in their place, by insisting they actually take a history and do a physical which differentiates Central Pain from all other conditions. The definitive test takes approximately ten seconds and was discovered back in the 1800’s by S. Weir Mitchell. It was confirmed by Carl Saab, one of the contributing authors here–now at Yale. We owe that marvelous institution known as Johns Hopkins Medical School, the flagship center for a very long time, to Mitchell’s efforts to bring in foreign doctors, such as Osler, to upgrade American medicine.

During the Civil War, Mitchell discovered that he could identify pain of central origin by applying light touch. If the pain was instantaneous, there was injury to a PERIPHERAL NERVE.  If the application of light touch required a latency of twenty or more seconds before exacerbation of the burning occurred, the pain was of central origin.  

He also established for his own mind that Central Pain was severe (despite his handicapping lack of a 1-10 scale) by noting that some of his bravest soldiers developed the temperament of “the most nervous girl” after acquiring Central Pain. This was evidence enough for Mitchell that nerve injury was terrible. He subsequently dedicated a wing at Hopkins to study of nerve injury.

Since then, things have gone downhill, until now Central Pain has shrunk in importance, until now it is in danger of being abolished altogether in medical terminology. After all, there are lots of other pain patients who offer up similar numbers on the 1-10 scale.  No one is looking to see if they have the temperament of a nervous girl. Either Americans are getting braver, or the disease is badly misunderstood.

However, there is still Dr. Gregory House. In Season 5, episode “Last Resort”, in order to induce very severe pain, House injects his fellow as well as the patient, with Capsaicin, in a small area. Both moan and wince. Capsaicin induces a burn something on the order of the dysesthetic burning of Central Pain. The House portrayal of Capsaicin injection may not capture much attention, but those of us who have to live with this, not just as a diagnostic test, but as a way of life, took notice of this episode. We also could not help thinking that while the two on House just had the pain in one little area, that many of us must endure it over the entire body.

So we are down to Dr. House, but because the pain is real, we know that eventually some real doctor will notice. He will have to “not care what others think” as much as House, because nearly everyone else is missing this symptom. That is because it is not THEIR pain. If it were, then nothing much else would be of concern.  Sound self centered? There is the Capsaicin on the pharmacy shelf, ready to test your moral judgments. Don’t forget to inject it everywhere.

This is a submission from one of the doctors here at painonline. Our thanks to the medical professionals who contribute:

“I remember giving a history and physical to my chief resident and including the comment that the patient was insane. The chief resident said, “You don’t have to include that. I can tell it from the history you are giving.” Do we sound any different in describing our central pain? In my thinking, it sometimes seems as if Central Pain induces a type of insanity. Either that, or the world itself becomes insane, so the person just struggles on. Perhaps it is really just exaggerated stress, rather than insanity, but there is clearly something wrong.

From what I know, and I study brain function, EVERY thought and brain function can be reduced to some chemical reaction. Chemoarchitecture of the brain is more important than anatomical structural architecture, although both are linked. Saying this, I believe the chemical processes of the pain system ARE insane in central pain. They do not make sense, they are disordered to the point of being counter to logic. If this is not insanity, it is close to it. So we become partners with some insane part of the nervous sytem, inside our own body.

This is not the same as loss of sensation, which would be a nothing. It is an active presence, which must be dealt with in thought and mental prioritizing. Since the pain is just a construct, which does not exist in the exterior world, it is a special enemy, rather than an imaginary friend. We cannot come to terms with it, because it does not want us to. Pain does not call for inaction nor being ignored. It sends alien voices to our happiness and reasoning. All these phenomena show how insane pain is acting in a damaged nervous system.

It is only natural to express pain openly or subconsciously. Yet, what we are expressing is an insanity. Hence, no one likes to deal with it.

Other than in very limited circumstances, I have never found that talking about it is helpful to anyone. It is not a message we can give them. And so, in general, we must live pretend lives. This permits those around us to grow and proceed on their ways as they must. We sit as flies on the wall, in agony, hoping for the best for others, although our preoccupation with suffering virtually guarantees that our active participation in their good will be minimal. We can only hope it will be enough. We attempt to constrain the insanity within ourselves, so that it will not harm our loved ones.

For us, this passes as righteousness (whatever that is), although inspired living is most difficult, if not impossible in the severe cases. This is because there is a focus on death when one is in longstanding terrible pain, which runs counter to the proper attitude toward life, and the gratefulness we should feel for blessings. Our gratefulness is miniscule, like the widow’s mite, but how are we to counter the evil.

When we are lost in the current of pain, it will carry us away. It does not help to think back to familiar territory. When we are in its grip, we must find a way to gain a little steerage, to deal with the situation we are in now. We must try to find something buoyant and hang onto it. This is different from directed travel. In this position, how does one choose right or wrong effectively. How do we find balance in life. I suspect that we do not, in fact, do this, in an objective sense. Loss of choice voids some of the accomplishment we feel in exercising our agency in life.”

Central Pain is the Dark Pain of suffering. Dark matter is thought to be responsible for the majority of gravitational pull in the universe, yet no one can see or detect it. It is an assumption from elimination and observation of how things operate. Watch a CP rat try to chew of its legs to relieve the distal pain of CP and you draw conclusions pain is there, but you cannot measure it. Actually you can measure it in rats by counting the increase in glia around the dorsal root ganglion cells which transmit pain, by studying neuroinflammatory chemicals and cytokines in the superficial lamina, maybe even by placing delicate probes into the zona incerta of the subthalamic nucleus, but these operations are not possible in the intact human.

You know dark matter is there because of the way things behave in nature, but dark matter is exceedingly difficult to see. In fact, it is not only impossible to see, it is also impossible to detect. Central Pain is not much different. Serious researchers in pain can observe the presence of central pain by the way people (or experimental animals given cord injury) behave, but there is no way to measure it. For that matter, any central pain patient will tell you they are simply using the words they have, but in fact, the physical agony is a new sensation, or perhaps a mix of existing sensations to the point they are unrecognizable.

The ordinary spinal cord injury person, focusing on mobility, is cheered on, or even driven on, to develop as much function as possible.

This is simply an extension of the principles of athletic training. No pain no gain. However, with sensory nerve injury pain, the principle may not hold at all. “No gain in pain” may be the real guiding principle. The question is whether rehab centers can do a one hundred eighty degree turn and advise those confronting central pain to pace themselves carefully, so that they do not become overdrawn on emotional resources. Is it possible to urge more performance on the motor side of things while encouraging avoidance of stress on the sensory/emotional side? It is a challenge, but there must be a realistic awareness that the central pain actually exists, is quite possibly terrible, and like any person in severe pain, some ongoing soothing of feelings is essential, if at all possible. This easing of stress may involve proper education of family members or even of the patients local physician.

The habit of trying to make patients keep moving forward, fighting as it were, can become a habit in medicine. It is not however a universal tool. Pain requires retreat, rest, withdrawal. If one watches a wounded deer, pain is there specifically to cause the animal to hole up somewhere until the pain lessens. Stopping movement and avoiding further injury is in fact the specific message of pain. It makes no sense therefore to assume that when severe pain arrives, the patient is to be “driven”. Ordinary people are permitted to live ordinary lives. Nothing could be further from the truth in central pain. When facing this suffering, the patient is typically told they must be a fighter, must get going, must write a book, must become a “superhero”. This is balderdash and runs counter to the bodies innate reaction to pain.

The same physician, if he does not think, will say that pain is a warning not to use the part to avoid further injury; and, with the other side of the mouth say that if central pain is really, really severe, then it is time to really, really get going, to prevent its immobilizing of the will..

Therefore, conservation of self (thin though the self may be in the identity eroding grip of unbearable pain) is usually the best weapon against pain. Since the injury will not heal, the most logical approach is to modify life so that less stress is coming at the person. This is not easy to do since the patient is trying to describe their plight to others in order to gain help. CP seems too heavy to bear on one’s own. Based on this hope, and a desperate search for some relief, many pain clinics prosper without any real solutions to offer. Their own prosperity is given as support for their efficacy, when in fact it is the severity of the pain, not the potency of the relief which is driving the system.

Most pain clinics fail miserably in treating central pain. This is not their fault because there are no medicines to dispense which accomplish such a thing. They are open for business, but the shelves are empty, yet they are doing a booming business. The irony is all over the operations. What they can accomplish is treating the non central pain, ordinary pain which often follows spinal cord injury. These pains come from the fundamental touchiness of spinal cord segments (C1, C2 etc down to S5) with aberrations in the precise configurations necessary for bending and weight bearing. The body is efficient and in the spine, every little structure has its function. The skeleton can sacrifice in some areas without fouling up every other bony part. The spine, however, is highly integrated. A shift in bearing or position in one area is likely to put abnormal loading on discs. It becomes just a matter of time until remaining discs begin to malfunction, soften, dry out, crack, shrink, herniated or give up. Most spinal surgery is a temporary matter, where pain is concerned. There is hope the new flexible polymers will be able to replace discs and provide the cushioning which has been missing in bone grafts.

There are MANY patients who do well and function happily after a bone graft for disc replacement. However, these happy campers tend to have a SINGLE disc replacement at ONE level without injury or displacement of the lamina, the facet joints or uncus (zygoapophyseal joints). Strangely medicine exists today accepting that the donor graft from the hip can and does often hurt for life, while the area in the spine where a great deal was removed and the hip bone inserted is going to be pain free. This really does not make sense.

For these secondary pains, there is justification for a system to monitor opiates or other meds. To avoid legal complications, many pain clinics refuse to dispense pain meds. This is quite a contradiction in terms. Others are simply unofficial drug store police, who remind one of a hall monitor of opioids. No matter how exacting a pain center is on dosing controlled substances, the perfectionism on record keeping and dosimetry has no influence whatsoever on the ability to help central pain. It is about methodology of compliance with the law and ethics, not about pain relief.

A truly functioning pain clinic would be very much like a social organization, getting the word out to society, organizing charitable fund raisers and in general acting like organizations dedicated to solving a medical problem. Consider, for example, Jerry Lewis and muscular dystrophy. That organization is fundamentally aiming toward research money. Pain clinics generally play no such function.

Some clinics are fundamentally anesthesiology driven. These naturally tend toward blocks of various kinds. There is also the technology of inserting catheters in the epidural space. While most success is about relieving spasticity, there have been some claims of help by steady release of opiates into the spinal area. While the reports on central pain are possibly valid examples of relief of neuropathic pain, the generalized failure of the pumps to stop central pain makes one wonder whether the pain relieved was actually CENTRAL.

Injury to the long tracts of the spine at any level, and also to the brain pain tracts at any level, is capable of causing central pain. This pain typically has “burning” as its most prominent aspect. However, the burning of CP has the paradoxical component of “cold”, so it is obvious we cannot simply use the word “Pain”. To consider whether spinal pumps are working for central pain, we need careful descriptions of what agonies are present, and which were benefitted, and to what degree. These descriptions are glaringly absent from the literature and so we cannot do much with it.

Pumps play an important role for many, but they seem not to work for many severe cases. Pain blockage usually does not work this way. Lidocaine makes EVERYONE go numb. Since the implanted pumps help SOME of the time, we are back to square one. We must make sure which type of pain is actually being benefited. The same may be said of the centers which use transcranial stimulation, either by DC current, or by magnetism. We must first be assured they know what central pain is, and what it is not, before we can weigh the benefit reported.

We do not know that pain clinics are breaking as many or more hearts than they ease. They are very expensive, and typically very regimented. A sick person in pain is not a good candidate for any kind of regimen. They may be too ill to travel, and require special accommodations for sitting. These accommodations are often absent from pain clinics. A person who saves money to travel long miles to a “pain center” may or may not benefit from being given some militaristic schedule for opiates, along with “CONTRACTS” which are aimed at protecting the doctors license, not at pain relief. This is not to say such measures are not necessary. It is simply that as we see buses going around town to conduct students to special schools, it seems something similar ought to occur for many who wish to visit pain clinics. Should they really be out of reach costwise for the severely injured patient, who is not fit to travel? We think not. The assumption that it is only pain, so the person can simply travel to the clinic is often an unintentional brutalization in itself. What is needed is some kind of pain ombudsman to advocate for the CP subject with the clinic.

Until actual cures are developed by the dedicated pain researchers, more effort at pain clinics should be directed at assisting at the social level. Large pain clinics should have therapists trained to educate the patients family about the adjustment and accommodations necessary to deal with central pain. This sort of assistance is available in nearly every other serious handicap. However, the obsession with preventing addiction seems to swamp other considerations when time is allocated at many clinics. In the meantime, every CP patient must take a careful measurement of their own resources and make sure they are retaining enough peace of mind to get by. It will always be in short supply when severe chronic pain is involved. Stress is to be minimized. Boredom and being “locked in” to the bare functions of life with no distractions for relief, is NOT a minimization of stress.

We take injured kids to camp for a little R&R. Shouldn’t pain patients have something similar. Maybe an official “friend” at the pain clinic. Maybe an occasional massage for the kinesthetic dysesthesia. Maybe a free subscription to cable TV. Maybe government could assist with stress producing situations, such as court appearance, or other compliance activities, which the stressed out CP patient finds overwhelming. Certainly, family counseling should be provided, not to chide the patient, but to reassure the family that their efforts are really necessary, that the CP person is actually very ill.

Hedging against stress, not demanding that anyone in severe pain ‘write a book” about their experiences (who wants to read that kind of whining anyway?), or “start” an organization” or “open a website” is more realistic than driving the sick person like a donkey to make superhuman accomplishments and really get involved in society. The wounded deer affect is in operation in central pain and it must be acknowledged. The deer does not withdraw from the herd for its safety, because the herd exists for its own preservation. Yet, the withdrawal may avoid endangering the herd. Nevertheless, it is necessary so that the deer can heal. Human, however, are not deers. The crowd, the public, the group can reach out to help the ill, just as it does for countless pains. Human compassion makes us more than intelligent apes. We should not ask what the injured person can do for us (make us feel competent despite our incompetence, by being “brave” a “fighter” a “book writer”). Instead society needs to help themselves along with us by devoting the resources to understanding how it is that the pain message is created by neurochemistry and neuroanatomy. In doing this, they will make obsolete the millennia old reliance on addicting opiates and move on to sophisticated medicine. An important offshoot will undoubtedly be a block for the neuropathic pain of Central Pain, which probably is not much different in its neurochemistry than ordinary noxious sensations in a healthy nervous system.

For every “hero” with central pain, there are hundreds collapsing in defeat as they find not only can they not do something extra, but that they cannot even do the ordinary day to day activity which life requires because they cannot handle the stress on top of their pain.

Presently, most of what passes for treatment of CP works via what is fundamentally sedation. Serious pain relief is not usually available for severe cases. And so, until that day when someone finds a way to close off the TRPV-1 calcium channel, or otherwise block central pain, we say, “Avoid stress”. You are not going to conquer your pain, you can only save your strength so it does not conquer you.

And to the pain clinics. We love you, even if you are wildly expensive. You are all we have. Please do more. And remember, our families are hurting too.

UM SCHOOL OF MEDICINE SCIENTISTS DISCOVER KEY BRAIN MECHANISM INVOLVED IN POORLY UNDERSTOOD CENTRAL PAIN SYNDROME

Findings Could Lead to Treatment for Painful Condition Common in Spinal Cord Injury, Multiple Sclerosis and Stroke Patients

            Scientists at the University of Maryland School of Medicine have discovered a key mechanism in the brain related to a devastating, painful condition that affects people who suffer from spinal cord injury, multiple sclerosis and stroke. The condition, called Central Pain Syndrome, causes chronic pain that patients compare to being stabbed with a thousand burning knives. The pain can be severe and untreatable and suicide is a leading cause of mortality among those who have the syndrome. Now, a team led by University of Maryland School of Medicine researchers has traced the syndrome to a malfunction in the zona incerta, or “zone of uncertainty,” an area of the brain about which little was known until now. Their study has been published in the online version of The Journal of Neurophysiology.

            “We hope that by understanding this underlying mechanism of Central Pain Syndrome, we can begin to think about potential treatments or preventive techniques,” says lead author of the study Asaf Keller, Ph.D., a professor of anatomy and neurobiology at the University of Maryland School of Medicine. “We are continuing our research into how the zona incerta is related to Central Pain Syndrome, and we hope to begin studying spinal cord injury patients who suffer from the condition very soon.”

            “This study is an example of the kinds of discoveries that are possible in an interdisciplinary environment like our School of Medicine, where world class researchers from every discipline have easy access to each other’s expertise,” says E. Albert Reece, M.D., Ph.D., M.B.A., John Z. and Akiko K. Bowers Distinguished Professor and dean of the University of Maryland School of Medicine. “We hope this work will lead to a solution for the patients who suffer so terribly from this now-untreatable pain condition,” say Dean Reece, who also is vice president for medical affairs of the University of Maryland.

            Pain travels from the limbs to the spinal cord to the brain. The zona incerta reduces pain by filtering out or inhibiting sensory cues it deems unimportant before they pass on to the rest of the brain. The zona incerta allows only certain pain information to be experienced by the brain. The study, called “Zona Incerta: A Role in Central Pain,” traced Central Pain Syndrome back to a malfunctioning zona incerta. The scientists found that the zona incerta in animals with Central Pain Syndrome is not inhibiting pain as it should. The zona incerta in these animals is allowing too much pain information through to the rest of the brain, causing the animals to experience unusually high levels of pain.

            Central Pain Syndrome affects as many as 80 percent of patients with spinal cord injury, about 30 percent of multiple sclerosis patients and almost 10 percent of patients who have suffered a stroke. The pain associated with the syndrome can be a heightened sensitivity to ordinarily painless activities as simple as putting on clothes or feeling the wind on the skin. The syndrome also causes spontaneous pain that occurs for no apparent reason and can be unrelenting. There is no treatment for the condition, and scientists have known little about the source of the pain until now. Dr. Keller published a paper five years ago that found the zona incerta was a filter that allows only certain pain information to move on to the thalamus, where it is processed. From the thalamus, the pain information goes to the cerebral cortex, where sensations are perceived.

            Dr. Keller collaborated on the new study with Radi Masri, Ph.D., an assistant professor at the University of Maryland Dental School and the Department of Anatomy and Neurobiology at the School of Medicine, and their colleagues Raimi Quiton, Ph.D., and Peter Murray, Ph.D., both postdoctoral fellows the Department of Anatomy and Neurobiology, and Jessica Lucas, a graduate student in the Program in Neuroscience, as well as Scott M. Thompson, Ph.D., a professor of physiology at the School of Medicine. The study was funded by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, and the Christopher & Dana Reeve Foundation.

            Co-investigator Dr. Thompson recently completed a study with his associate Gexin Wang, Ph.D., a post-doctoral fellow in the Department of Physiology at the School of Medicine, showing that animals with Central Pain Syndrome respond to a drug called ethosuximide, a U.S. Food and Drug Administration-approved treatment for childhood epilepsy. Dr. Thompson’s study found that ethosuximide appeared to calm the over-activity and excitability in the thalamus that seems related to Central Pain Syndrome. Some of that excessive activity may be a result of inactivity in the zona incerta, according to Dr. Keller’s and Dr. Thompson’s latest joint study. “Our two studies examine areas of the brain that are very near each other, very similar and clearly related,” says Dr. Thompson. “We believe our two studies are basically indicating the same thing — that there is some imbalance of activity in the thalamus. These studies could finally mean relief for these patients for whom there is really no treatment. They’re desperate for anything.”

            The scientists plan to continue their research to investigate new treatments and ways to prevent Central Pain Syndrome. Dr. Thompson will begin a study of ethosuximide in human patients very soon. Since that drug already has earned FDA approval for treating epilepsy, if it proves effective in Central Pain Syndrome it could be approved for treating that condition far more quickly than a new drug.  

            Dr. Keller is planning to investigate other avenues as well. His study showed that, after an injury to the spinal cord, the zona incerta gradually stops working properly over a period of several weeks. Dr. Keller and his colleagues hope to find a way to intervene during those weeks and keep the zona incerta active. “We’re considering options such as non-invasive brain stimulation, stem cell implants or even occupational therapy — exercises patients could do to stimulate the zona incerta,” Dr. Keller says. “A successful treatment regimen one day could include a combination of exercises and drug therapy. We’re hopeful we’ll find relief for these patients, at last.”

They also confound cliniicans who often confront ACTUAL musculoskeletal pain in post spinal cord injury patients, which pain is NOT neuropathic. Devising treatment strategies is much more difficult because verbal descriptors are lacking by which the clinician may distinguish between Central Pain in the muscles and the musculoskeletal pains which are to be expected whenever there is alteration anatomically at any motion segment of the spine. The former is neuropathic, and may be utterly resitant to opiates, while the latters is nociceptive and should respond to conventional pain therapies, such as opiates.

In a prior article here, the increasing focus on the posterior nucleus of the thalamus was discussed. This largely ignored nucleus is at the very back of the thalamus. The prior article dealt with connections being uncovered between pain tracts and the posterior nucleus or PoT (also called PO)

Now Masri, Keller and others at the University of Maryland have published a landmark study in the online J. Neurophysiology April edition ** which suggests that the PoT has inhibitory input from the zona incerta. The zona incerta is part of a nucleus which sits BELOW the thalamus, known as the Subthalamic nucleus. The Subthalamic nucleus is itself divided into areas. Nothingi n the brain seems to do just one thing. One neurophysiologist suggested that no area of the brain does just one thing, and that no nucleus has more than thirty percent of its neurons devoted to any one function.

Zona Incerta has always been a mystery as to its function. Its very name means in Latin, the zone of uncertainty, meaning no one had a clue what it did. (If you want a little look at this area, go to Brainmaps.com) Now, the ZI is turning out to be massively important to Central Pain patients. Its failure to inhibit the PoT may be the actual mechanism of CP.

This multifunctional aspect is revealed in the zona incerta. However, proximity often means some RELATION between the various functions should be suspected, or at least looked for. The posterior part of the Zona Incerta is the area of interest. The very most posterior part of the ZI is the area which is sometimes lesioned in Parkinson’s because there are links to the cerebellum and hence the motor functions of the body. (Coordination etc) The forward part of the most posterior region of the ZI was discovered to serve the function of INHIBITING the POT. When Central Pain is present, the inhibitory signal from the ZI is missing.

This leads to the rather logical conclusion that without input from the ZI, the PoT cannot distinguish between something like a breeze on the skin and a burn. (The University of Maryland news release on the discovery called Central Pain a mysterious disease. Perhaps an analogy might be made to color blindness. The color blind cannot distinguish between red and green. Thus, the brain of a person with Central Pain cannot distinguish between a breeze on the skin and a burn)  

The clinical description is hardly surprising, since most of those in the survey here attest to the fact that anything bringing a temperature change, especially a blast of cold air< will evoke burning pain powerfully. However, the more the press refers to Central Pain as “mysterious”, the less mysterious it becomes. This alone is a help to CP subjects. Even more help is the notice that attention and focus must be given to the surprising role of an allegedly ”MOTOR” area, the Zona Incerta, plays in interpretation of pain signal. Perhaps we should say “sensory signal” since most of what causes agony in CP is not inherently a pain stimulus at all.

Carl Saab, noted for identifying an area in the cerebellum which inhibits central pain, ie the vermis, has written here of the unexpected cerebellar link between that structure and pain inhibition. His first paper on the subject was so unexpected that it caused not only an uproar, but anger, at the Ninth World Congress of Pain, when Dr. Saab presented it. However, we now have more backing for the former author at painonline in yet another link between the cerebellum and pain. Namely, the area which connects to the cerebellum, and is a point of interest in Parkinson’s, is immediately adjacent to the pain interepreting area of the posterior region of the ZI which inhibits the PoT.

Look for more material on this, as some Parkinson’s patients have pain. It may be a touch of central pain, given this recent finding. We congratulate the authors (there are a number) and feel this may be the most significant article ever published on Central Pain.

**We are indebted to Mary Simpson for first noting this article when it appeared.

1) PAIN IS EITHER NOCICEPTIVE (ORDINARY aka NOXIOUS PAIN) OR NEUROPATHIC (NERVE INJURY PAIN). NEUROPATHIC PAIN MAY BE EITHER SPONTANEOUS OR EVOKED.

5) CENTRAL PAIN IS WORSE WHEN IT IS SENSITIZED, I.E. EVOKED, ENHANCED OR ELICITED

6) EVOCATION OF CENTRAL PAIN CAN OCCUR FROM EITHER NON PAINFUL STIMULUS (ALLODYNIA) OR PAINFUL STIMULUS (ALLOPATHIA). TOUCH IN ONE AREA RESULTING IN PAIN IN A NEIGHBORING AREA IS KNOWN AS ALLACHESTHESIA (EPHAPTIC PAIN).

7) WHEN THE EVOKING STIMULUS IS PAINFUL THERE IS FREQUENTLY CONFUSION AS TO WHETHER THE PAIN IS NOCICEPTIVE OR NEUROPATHIC, BUT IT MAY BE CONSIDERED TO BE BOTH

EVOKED CENTRAL PAIN IS VERY MUCH MORE SEVERE THAN SPONTANEOUS CENTRAL PAIN

9) PAIN MEDICINES WHICH REDUCE THE SENSITIZER (EVOKER) OFTEN OWE THE RESULT TO THEIR EFFECT ON THE NON-NEUROPATHIC ELEMENT. THE MOST COMMON NONPAINFUL EVOKERS ARE LIGHT TOUCH, COLD, AND MUSCLE LOADING. THE MOST COMMON PAINFUL EVOKERS ARE SHARPNESS, MORE SEVERE COLD, AND CONFINEMENT IN ONE POSITION.

10) PAIN MEDICINES WHICH DO BENEFIT EVOKED PAIN BY BLUNTING THE PAINFUL SENSITIZER MAY HAVE NO EFFECT WHATEVER ON THE SPONTANEOUS CENTRAL PAIN. SEDATIVES AND MEDICINES WHICH QUIET THE CENTRAL NERVOUS SYSTEM (ANTICONVULSANTS) SEEM MORE EFFECTIVE AGAINST THE SPONTANEOUS CENTRAL PAIN AND PAIN WHICH IS EVOKED BY NONPAINFUL STIMULUS.

11) RESEARCH REPORTS THE MOST SEVERE CENTRAL PAIN IS FOUND ONLY IN THOSE WITH  SOME REMAINING FUNCTION, HOWEVER MINISCULE, OF THE SPINOTHALAMIC TRACT

12) LOSS OF MOTOR FUNCTION DOES NOT CORRELATE WITH DEGREE OF CENTRAL PAIN.

13) SEDATION AND STRESS AVOIDANCE ARE GENERALLY THE MOST THAT CAN BE OFFERED AGAINST SPONTANEOUS PAIN, ALTHOUGH CONVENTIONAL PAIN MEDICATIONS MAY TREAT SENSITIZING STIMULI OR SENSITIZING PAIN.

14) IN GENERAL, THE MOST SEVERE CENTRAL PAIN CAN BE EXPECTED WHERE SIGNIFICANT RETENTION OF SPINOTHALAMIC TRACT IS PRESENT. SUCH PAIN TYPICALLY APPEARS WHEN CORD INJURY IS RESOLVING AND THE INJURY IS REVEALED TO BE INCOMPLETE.

15) DECREASE OF AMPLITUDE IN THE MID OR LATE PEAK SOMATOSENSORY EVOKED POTENTIALS MAY CORRELATE WITH THE PRESENCE OF CENTRAL PAIN IN SOME CASES, BUT ELECTROPHYSIOLOGY LABS DO NOT AT PRESENT TYPICALLY INCLUDE THIS ANALYSIS.

16) THE DEGREE TO WHICH SPONTANEOUS CP CAN BE EVOKED VARIES FROM INDIVIDUAL TO INDIVIDUAL, THIS IS TRUE BOTH AS TO THE DEGREE OF HYPERSENSITIZATION AS WELL AS THE NATURE OF THE EVOKING STIMULUS. TYPICALLY, ONLY THE BURNING DYSESTHESIA AND MUSCLE PAINS MAY BE PREDICTABLY EVOKED BY NONPAINFUL STIMULUS. (PINS AND NEEDLES MAY SOMETIMES BE EVOKED BY COMPROMISED CIRCULATION TO AN EXTREMITY, OR ODDLY, WITH COLD.)

17) JUST AS IN A BURN PATIENT, THE PERCENTAGE OF SKIN SURFACE AFFECTED BY BURNING DYSESTHESIA CORRELATES WITH THE SUFFERING OF THE AFFECTED INDIVIDUAL. THOSE WITH CP ON TEN PERCENT OF THE BODY TYPICALLY FIND THE PAIN LESS UNBEARABLE THAN THOSE WITH CENTRAL PAIN ON 90% OF THE BODY, BARRING CONFOUNDING BY EVOKING STIMULUS.

18) THE SPINOTHALAMIC TRACT MUST ACT OR TRANSMIT SIGNAL, AND MUST DO SO ABNORMALLY, BEFORE THE THALAMUS WILL SIGNAL PAIN TO THE CEREBRAL CORTEX. AN ABSENT STT SIGNAL YIELDS NO PAIN.

19) SINCE THERE ARE BOTH LATERAL AND ANTERIOR SPINOTHALAMIC TRACTS, CP CAN BE EXPECTED TO DIFFER ACCORDING TO THE ANATOMIC INJURY INVOLVED AND WHICH INDIVIDUAL PORTIONS OF THE TWO TRACTS ARE DAMAGED.

20) CENTRAL PAIN IS A MIX OF PAIN SENSATIONS, EACH OF WHICH MAY BE RELATIVELY INDESCRIBABLE, AND MORE SO THE COMBINATION OF THE INDESCRIBABLE PAINS, WHICH MAY MERGE IN A WELTER OF SEVERE BUT INARTICULABLE SUFFERING…

The most severely injured area of the central nervous system is the least likely generator of central pain. Such pain is rather more likely to have its origin in nearby, less severely injured areas of the cord or brain. Hence, present methods of MRI acquisition are not accurate in identifying the presence nor the originating area for central pain.

It has long been known that incomplete spinal cord lesions are more likely to result in central pain than complete. What has not been as widely appreciated is that any retained function in a damaged spinothalamic tract carries the risk of severe pain, the more retention the greater the risk, presuming actual damage and loss of normal operation of the tract.  Thus, we find quadriplegics who are completely numb, but have no pain. By comparison, we find walking quads with really severe pain.

The closer to complete a lesion is, the less severe the CP is likely to be since there is less disordered spinothalamic activity to make things haywire in the thalamus. This is, however, far from a universal rule, since there are certainly ”completes” with very severe central pain. These unfortunates may have portions of the ST tract which function in the absence of real sensation. What is often ignored is that sensitization of ANY central pain can create a very severe pain situation. The ordinary pain contributors, ie nociceptive pain which frequents the lives of some completes, can sensitize central pain. Once the cycle has begun, it can be evinced or evoked to a high level. So in most cases, when comparisons are made, one is discussing the spontaneous burning, not comparing evoked levels of pain, which are subject to MANY variables.

Damage to one part of the many faceted spinothalamic tract does NOT mean equal damage to all parts.

Although not proven to exist in humans, primates thus far studied have both a lateral AND an anterior spinothalamic tract on both sides of the cord, subserving slightly different modalities. Injury with partial preservation of any part of the tract could be expected to yield very severe dysesthetic pain, both as to touch or temperature and as to muscle loading. It is as if the thalamus expects to see a certain type of waveform signal indicating all is well. If it receives NO signal, there is no pain. However, a signal departing from normal results in a message being sent from the thalamus to the cortex that things are seriously wrong.

In other words, even if the thalamus cannot sort out the type of pain being transmitted by the injured tract, a novel or distorted pain signal will be the result. This unuusual pain is “protopathic” pain, which is to say, the primitive burning retained by an injured nerve fiber after all other pain sensations have been lost. This type of pain can be demonstrated by taking a blood pressure cuff and compressing the arm for a time, and watching pain modalities disappear one by one. (Do not attempt this yourself, as it must be done under medically controlled conditions to insure that no permanent nerve damage occurs). The last pain to persist, before the arm goes completely numb, is protopathic burning, which is thought to be indistinguishable from dysesthetic burning. Central Pain is a melange of pains and contains more than just protopathic burning. There is always a MIX of pains, even in what a CP patient will call “burning”. Common other sensations present are paradoxical cold and wetness. In central pain, touch at one location may occasionally evoke pain at another location (usually nearby the point of stimulus or at least on the same extremity) , which is called an “ephapse”. This phenomenon of ephapse is not known to occur in the protopathic demonstration.

This experiment can be viewed as somewhat similar to passing a light through a prism, which reveals that what was seen as white light is actually composed of the combination of many colors. Similarly, pain can be sorted out into various elements, the most primitive being termed “protopathic”. The last pain to go in an injured nerve is a poorly localized diffuse burning, which is known as “second pain”. This pain lacks discriminative features as to loccation and nature. It is similar to the flare which is felt AFTER one withdraws a hand from touching a hot stove.

“First pain” is the pain felt on touching the stove, and the flare afterward is the “second” pain. Second pain is ,mainly just THERE, and the brain is not so worried about the precise location on the body as it is signalling PRESENCE. The important role of second pain is to let the person know that some general arear of the body is injured in order to drive appropriate action.

However, in actual central pain, burning dysesthesia (which is akin to second pain), the signal does not stop. It may be enhanced or evoked by sensitization, the source of which need not be painful and in fact usually is not painful. Light touch, a rush of cold air, clothing, or even movement may result in evocation. Patients, as well as clinicians have a very difficult time sorting out evoking painful stimulus from core central pain. It is easy to separate non noxious stimuli from central pain since experience teaches that such stimulation should not be painful. However, the situation is much more difficult when the evoking stimulus is itself painful. Sensitization by painful stimulus often or usually leads to confusion in the mind of the CP patient, who frequently confuses the nocicptive sensitizer with neuropathic central pain. This phenomenon is responsible for the many inaccurate and confused descriptions of central pain found in the literature which incorrectly class many normal pains with central pain. If you have ever felt the precise pain BEFORE the cord/brain injury, then that pain is NOT central pain. Central pain occurs ONLY in dis-integrated pain pathways. If you can describe it accurately, and the doctor recognize it, then it is NOT central pain. Central pain is by definition “bizarre” and is the result of a diseased pain pathway.

The same confusion occurs in therapy. Those with central pain, who have nociceptive pains sensitizing the central pain, may find opiates relieve the sensitizer. It has never been conclusively proven that opiates affect core central pain, although the perception persists among the majority that it is helpful. The benefit is likely to be based not on relief of dysesthetic burning, but rather footed on quieting of the central nervous system, as in sedation, or in relief of the sensitizer.   This position, that sedatives are the first line drugs for CP, is far from universal with many good pain doctors holding that opiates are good medicine for central pain. However, based on the survey results, this benefit is most likely to accrue when the CP is mild or moderate. For those with severe pain (usually the moderte-severe cutoff point used is the inability to tolerate the touch of clothing) the majority feel sedative by any agent, such as hypnotics or anticonvulsants, is equal in benefit to opiates or opioids, leading to a suspicion that sedation is at the heart of much of the response to opioids in general.

Dysesthetic burning nearly always is accompanied by a mix of other pains, some of which may be quite severe. These may include lightning or lancinating pains (intense but not lasting), pins and needles, and frequently the sensation of muscle cramps or soreness. The muscle pain may be so severe as to create paralysis, despite an intact motor unit. These neuropathic pains are often, if not always, confused with the many musculoskeletal pains which are typical of someone whose spinal cord has been altered by injury and surgery. The articulations of the spine at its motion segments are relatively unforgiving and it is rare to find a spinal cord injured person who is pain free from motion, even if their pain is not neuropathic pain. Normal pain is called nociceptive pain in the medical literature and the presence of central pain by no means guarantees one will not have nociceptive pain.

Dr. Ron Tasker, a distinguished neurosurgeon from Western Toronto Hospital and long the most published author on central pain was the discoverer that pain is carried in the spinothalamic tract (STT). Tracts in the spine are typically named after their origin and destination amd so we have ”spinothalamic tract”. These are present in two locations, both the anterior and the antero-lateral regions of the cord.

In the early work by Dr. Tasker, a distinction was not made between lateral and anterior STT tracts; and such a distinction is still not possible since the size of these tracts is below the resolving power of MRI or any other imaging modality. THe STT should be viewed as constructed similar to telephone wires, with multiple discrete bundles.

In the case of the spinothalamic tract, which originate in spine and ends at the thalamus in the brain, there are really multiple tracts. The assemblage of tracts winds around other tracts, including the tract which senses heat. Even if all the STT tracts were combined as one, it would still be too small for the resolving power of MRI. Consequently, significant injury in the STT may not show anything on MRI. Studies have revealed that those with the worst pain typically have no lesion visible on MRI, and where the MRI shows a bright lesion, there is typically NO PAIN. The treating physician must therefore not fall into the trap of thinking nothing visible on imaging studies contradicts the patients description of pain. The history of central pain is so unique that careful examiners have always found that verbal descriptors alone are very reliable in diagnosing central pain following injury to the spinal cord or after stroke (where the central pain is typically unilateral on the body). Central pain grows worse distally on the extremities and body; whereas malingerers typically have symptoms without gradation, eg “my whole arm is numb, or my whole leg is pained equally”.

The centripetal distribution of central pain is unique. When present on the face, this layering out or zoning of gradations of pain, ie distalization, was termed “onion peel skin” by Dejerine and Roussy. They were referring to the fact the pain grew worse as one went out along the trigeminal nerve, toward the tip of the nose and the center portion of the lips and gums. The requirement for partial damage was noted in the paradox that those with lesions high in the trigeminal fibers typically had the worst pain in the LOWER face, presumably because the most intensely injured nerves could not generate central pain, but those nearby which were partially spared displayed the dysesthetic burning.

This puts the central pain patient in a difficult position, since third party payers may read a negative MRI report as evidence against pain. Somatosensory evoked potentials (SSEP) may be of some help to certain CP patients whose pain is disputed. Recently, there have been some studies which show that latency or lowered amplitude in the mid and late peaks on somatosensory evoked potential may correlate with pain in the lateral pain tracts (an explanation of function of  lateral pain tracts in the thalamus is beyond the scope of this article, but other articles at this site explain the difference between medial and lateral thalamic pain). However, many centers doing SSEP have little or no  experience in evaluating mid and late peaks and central pain.

The few CP subjects who have answered the survey who were aware of their SSEP results have ALL shown abnormalitiies on SSEP; however, the wording of the survey did not anticipate the necessary refinement and so painonline cannot provide sufficient data to support the recently published studies. Each of the peaks on SSEP tracings have names and doctors do not typically discuss such matters with patients, and among themselves typically focus on the EARLY peaks, not the mid to late ones.

SSEP has traditionally been associated with damage to the posterior columns, which are MOTOR tracts, and only recently is there a suggestion that correct application of SSEP may be able to pick up the person with Central Pain in some cases. See eg Kakagi et al  “Pain related somatosensory evoked potentials J Clin Neurophysiol. 2000 May;17(3):295-308.

Central Pain has long had and is still undergoing a definitional problem.  Currently, in the literature, it is often confused with long term potentiation, central sensitization, and other conditions. However, traditionally, the definition of central pain is novel or bizarre burning which accompanies loss of superficial sensibilties after injury to the central nervous system. This “dysesthetic” burning is continual andspontaneous (many of the concommitant central pains are NOT continual) but typically can also be evoked by light touch. By usage, central pain is frequently used to name any and all pain which follows such things as spinal cord injury. This is short sighted. Musculoskeletal pain as is often seen when spinal function is abnormal can evoke or make more serious the central pains, but these phenomena should NOT really be lumped together, even if painful stimuli can evoke the central pains in some people.

We will stick with the traditional definition to avoid confusion.  However, one can expect serious misunderstanding. For example, a recent textbook on pain by an anesthesiologist states that some people with central pain find it “distressing”. Of course distressing might just as well be applied to the frustration when one cannot find the remote or if one runs out of strawberry marmalade. It is not a good word to use when describing central pain, in our opinion.

This word, “distressing” rightfully applies only to the most mild of the central pains, and hardly reaches the classic form, which may include some of the most intense pains known to man such as the lightning pains, which are mercifully brief, unlike the durable burning). LIghtning pains are not mild in tertiary syphilis, and they are no less severe in CP.

These central pains can be and usually are multiple in nature. Severe instances are among the most severe pains known to man. As Beric described, the pain of movement may be so severe that the personal is functionally paralyzed. Light touch may be so hypersensitized that the touch of clothing cannot be endured. It is hard to understand how an author could choose “distressing” as the most accurate descriptive term. Waking up during surgery from inadequate anesthesia would be “distressing” but it would also be “horrific”. Of course, MOST people with pain after spinal cord injury are not in severe agony, or perhaps have no pain at all. Burning in the majority may be likened to a sunburn, permitting clothing, motion, and thermal variation. The question is whether these patients represent REAL central pain, or whether they are merely a form fruste example of the disease. The foregoing paragraphs illustrate the definitional problem.  One correspondent to the painonline editorial staff has such severe muscle pains than it takes perhaps ten minutes to type one line. What word do we use for that level of central pain in the motor apparatus. Whatever it might be, “distressing” would not be it.

One wonders whether this particular author has seen and followed CP patients in sufficient numbers and  to a sufficient degree for accurate description. Less than ten percent of those in the survey in describing their central pain used a word which could be synonymous with ”distressing”, while more than thirty percent chose “unbearable”, “agonizing” or the like. The remainder used terms equivalent to “very painful”, “disabling”, and similar descriptive and verbal characterizations. One must be in relatively good shape even to make it to the pain clinic, and there are certainly those who find it impossible. For the person who operates in a very narrow range of endurable temperatures, a visit to the doctor may represent a genuine ordeal. Considering the large amount of world literature on neurosurgeons who have done brain ablation for central pain (unfortunately not very sucessfully), it is hard to imagine doing such a procedure for something which was merely distressing. And so we conclude that the author has seen mostly the more fortunate, and does not have the measure of severe central pain at all.

The painonline database, which is included in the Wall/McHenry database, is the largest collection of verbal descriptors of central pain in the world. One might argue that those less affected were not motivated to take the time to complete the survey, but this is speculative. The number of Central Pain patients among Dr. Kevorkian’s patients is mute witness to the impact on life which this terrible condition wreaks in its severe forms.

When there is a group of patients, suffering greatly, it has been common practice to ask the patient to rate their pain from 1-10. This is the so called “analog scale”. It has proven inadequate to the task since the stoic who has incredible sensitization with touch or themal stimulus, typically cold air, may rate the spontaneous central pain as a 4 or 5, when that very pain may be so severe that it makes the wearing of clothes, or even the taking of a step too painful to endure.

There has also been a tendency to assume that the more severe the motor injury, the more severe would be the pian. This assumption was NOT born out by the survey. In fact, just the opposite is the case. While those with most severe motor injury tended to have more normal pain, also called musculoskeletal, than those with lesser numbers of procedures, it was clear early on that the incompletely injured patients rated their pain as considerably more disabling and severe. In other words, a quadriparetic was more likely to have severe central pain than a quadriplegic. Furthermore, the central pain nearly always first appeared when the injury was first shown to be incomplete; ie when some motor function was noted to be returning.

The reason for these nonintuitive findings is that some function must remain in the spinothalamic tracts in order for central pain to be propagated and more especially for peripheral messages to evoke or hypersensitize the pain tracts, in order that hte most severe central pain be experienced.

Recently,  A.R. Hari et al  showed specifically that “the spontaneous recovery of human STT function (within the first year after SCI) in subjects suffering NP [neuropathic pain] is enhanced compared to those not affected.”

Also, “the correlation between current pain intensity (assessed on average 5 years after SCI) and extent of functional recovery substantiates the close relationship between recovery of STT function and the occurrence of NPthe correlation between current pain intensity (assessed on average 5 years after SCI) and extent of functional recovery substantiates the close relationship between recovery of STT function and the occurrence of NP” See Exp Neurol 2009 Apr;216(2):428-30. 2009 Jan 7 “Enhanced recovery of human spinothalamic function is associated with central neuropathic pain after SCI.”

These findings indicate once again that in evaluation those with spinal cord injury, stroke, mutliple sclerosis, traumatic brain injury, and the other conditions which lead to Central Pain that clinicians must be very careful to distinguish between motor and sensory impairment, and to realize they may correlate inversely so far as central pain is concerned.

This is by no means a statement of general applicability. Witness the article by Alan Hess, the all time most visited article at painonline, wherein we learn that this quadriplegic has central pain so severe that he cannot tolerate clothing, nor even the roughness of transportation. One may find among the quadriplegic some with the most severe form of CP, but statistically the likelihood of such a condition is more likely among the incomplete lesions.

The important point is that the clinician must listen to the patient. Nearly always, learning of the modifications in life style necessitated by the CP will reveal the force and severity of the pain, in many cases more so than the analog scale or any other evaluative method. It is a mistake to assume anyone for whom CP is severe is a weak individual or maladaptive. Who can adapt to unbearable pain?  This would be an oxymoron. Adaptation may better be expressed as “slowing the deterioration”.

Pain eventually wins. One may derive satisfaction in remaining quiet about it, in holding to morals, in attempting to perform productive acts, but sooner or later, really terrible pain begins to make inroads into the identity and radically alter life style. This defeat tends to come quickly in severe cases of central pain.  The patient is often shocked at the emotional lapses and gaps appearing in the psyche and assistance and relief all too frequently arrive too slowly because the pain is invisible to others. Proper treatment must ANTICIPATE the need.

in the most severe forms, such as severe central pain, the human apparatus does not strengthen with continued torture, and it would be unrealistic to expect humans in this state to grow strong and mighty, or immune to pain. Keeping one’s hand in a flame does not render the remainder of the body immune to burning sensations.

There has been entirely too much talk of the “mind body” in central pain, reflecting ignorance about the nature of perpetual and nondimniishing physical agony.  One may devise methods to minimize the impact of pain, such as the avoidance of stress and the adrenaline and angiotensin which flows from it and makes pain more alarming, but few CP patients find their dysesthesia lessened by the years, nor do they find themselves better able to deflect it.

The development of coping mechanisms is not synonymous with pain relief. If one is ugly, learning to overlook critical looks of others does not remedy the ugliness. If it cannot be fixed, it must be borne. Window dressing is available, orthodontics and even bone surgery, but as to central pain, no plastic surgeon can remedy the situation. It is invisible in its presence and equally as invisible in its absence. Thus, the clinician MUST LEARN to take a good and reliable history. Such a history ALWAYS centers on what modifications have been necessitated in life style. This is generally the most reliable indicator of pain severity. The doctor can make general judgments about the coping ability of patients, but should never assume poor coping equals slight pain. It is only logical that those most in pain will have the most difficulty. Additionally, motor impairment does not equal pain impairment. They are independent matters.

If one has severe central pain, the discovery that beautiful music or certain distractions relieve the stress of pain and the focus on it is not necessarily the precise equivalent of pain relief, or is it?  In any event, no music is sufficiently beautiful to block out the sensation of a hand immersed in the flame, and the same may be said of burning dyseshesia. Refuge in sedation is helpful, but actual pain relief is needed. There is still an active debate on whether opiates can benefit central pain. This dispute always runs into definitional problems.  If we sedate a patient and reduce the alarm and emotional devastation, have we reduced the pain. It is almost a semantic issue. Suffice it to say that the NIH has declared there is as yet no satisfactory treatment for severe central pain. The patient himself/herself will learn how to avoid EVOKING the CP, but the durable and tormentious spontaneous pain is another matter.

This is not to say that that other conditions, such as facet syndrome, muscle conditions, etc may not yield severe pain in the absence of STT function. It is not entirely clear how normal pain nor neuropathic pain reaches the brain. We know some, perhaps most of the pathways, but are ignorant of the algorhythms by which they interact. Indeed, the whole field of thalamo-cortical and cortico-cortical interactions and the six layers of cortex in which this occurs is a study still in its infancy, not only as to pain, but as to matters in general.  Pain inhibition pathways are even more poorly understood than pain excitatory pathways. Most statements in this area must be viewed as speculation, especially as it applies to the psychological aspects of pain. Assumptions about central pain drawn from observations of nociceptive pain are freqeuntly naieve, unjustified and premature.  Consequently, we must learn not to lump all these things together. Each patient must be evaluated individually. Until we have a specific reliable way to measure such pain, we must take the patient at his/her word, and accept ten people who exaggerate pain to avoid overlooking the ONE patient with terrible, unbearable agony because their motor loss is not complete.

            Eighty five percent of those responding to the question on the survey indicate that cold is a more rapid and powerful sensitizer (causing an evoked or heightened level) of their dysesthetic burning than heat. What can the explanation for this be??? See below.

Please note that in this article, the word Layer and Lamina mean the same thing, referring to the Rexed layers of the Spinal cord, which have the lowest numbers most superficially. Layer I is the marginal layer, where single C fibers have been documented to sensitize as much as half of the body. Layer II, the substantia gelatinosa, is the traditional pain layer. C fibers ascending to the dorsal root ganglia and horn of the cord recruit the big powerful A fibers to make for hypersensitization of the pain system. C fibers themselves are slow and imprecise.  We are learning that the traditional view that Layer II is most of the pain story is probably wrong. Somatosensory area I in the brain (the posterior ridge of the central sulcus) probably tells the LOCATION of the pain, Somatosensory II (parietal cortex) probably determines the SIGNIFICANCE of the pain, and the insular cortex appears to create the PAINFULNESS of the pain. It is still the majority viewpoint that Layer II feeds to SSI, the central sulcus. Pain ascends in the multistranded tracts which are known collectively as the spinothalamic tract, but this is a tract like telephone wires in a bundle are a tract. Dr. Patrick Wall, co founder of Painonline, in  1985 traced out as many as SEVEN discrete spinothalamic branches feeding into the thalamus.

As described in earlier articles, the thalamus, which is really two structures, there being one on each side of the brain, sits more or less straight back from the eyes at the center of the brain structures. The thalamus is probably far more important than we know, and we know quite a bit. One of the authors here, Dr. Francis Crick, even published a book opining that the human perception of the soul resides in the thalamus.

Just as identifying the part of the brain responsible for pain has been very difficult (although Dr. Crick and Dr. McHenry’s article here on the insular cortex broke new ground in locating the site of the painfulness of pain, ie. the insular cortex, scientists are presently trying to determine precisely the origin of fibers which carry pain to the insular cortex.

Al-Khater et al writing in the J. Comp Neurol 2008 Nov 1:511(1) 1-18 performed surprising studies which identified the posterior triangle of the thalamus (ie. the very caudal end) as the site which apparently feeds TO the insular cortex, where the painfulness of pain is appreciated. This pathway, the PoT nucleus pathway, is probably very important in central pain. This nucleus has not been included in prior studies of the pain in the thalamus because it was assumed that pain went to the VPM and VPL nuclei of the thalamus. Now we have a new area which seems dedicated to painfulness. This certainly bears further examination.

The spinothalamic cells which travel in the deeper lamina of the cord feed to the PoT. In the rat, there are approximately 90 spinothalamic neurons per side, some of which feed ONLY to the PoT.  The authors state that “85% of the lamina III/IV NK1r-immunoreactive neurons in C6 and 17% of those in L5 belong to the spinothalamic tract, and these apparently project exclusively to the caudal thalamus, including PoT.

Considering that few neuroscientists are even aware of a nucleus at the extreme end of the thalamus relating to pain, these scientists deserve credit for identifying a likely pathway for modulation of painfulness of pain.

These authors found that ONE THIRD of the pain transmitting neurons going to the posterior thalamus respond to thermal heating, while TWO THIRDS respond to cooling.

Those with central pain have always found that hypersensitization of the BURNING dysesthesia is more rapidly and powerfully evoked by a cold blast of air than by heating. Davidson et al may have an anatomical explanation for this paradoxical clinical feature of central pain. More work is certain to be done on the posterior thalamus.

Following chemotherapy and other incidents, nerve injury pain in the peripheral nervous system is rather common. Peripheral nerve injury pain has generally improved or ended over time if the severed neuron was able to grow back down the axon sheath and find the area it was intended to supply. This reconnection appears to shut off the pain. The alerted brain has been quieted. Such events are not available in central pain because central injury does not preserve a channel or empty axon sheath into which a regrowing neuron can track. Instead, there are many sprouts and the near end of the injured neuron, each of which is spewing out pain exciters, such exciters playing a dual role in hypersensitization and initiating regrowth.

Wernig et al in Proc Natl Acad Sci U S A
May (2008) have achieved a real breakthrough. They have been able to convert fibroblasts to neurons. These converted cells form into neurons, glia, and even dopaminergic cells. There has always been concern that converted cells might form tumors, but these scientists painstakingly separated the cells turned into neurons from pluripotential cells with fluorescent stains.

Certainly it is gratifying for scientists to finally unmask the transcription factors which will enable the formation of pluripotential cells into neurons. These transcription factors are:
transcription factors Oct4, Sox2, Klf4, and c-Myc

One can only hope the work will reach central nervous system neurons. The wheels of pain research grind slowly, but they grind exceeding fine.

High energy phosphate bonds are the batteries on which the body runs. These high energy phosphates transfer electrons to other chemicals in the body and change them from inert to active.

Reiterating, a kinase is an enzyme which phosphorylates, or links high energy phosphate bonds to chemicals, such as proteins (chains of amino acids greater than 200 in length) to make them active. Peptides, which are chains less than 200 amino acids in links can also be activated by phosphorylation. ATP is not the only phosphorylater but is the most important. Once it is activated by three high energy phosphates, it hands one off and become ADP.

Thus, the prime example of such an energized compound is ATP (adenosine triphosphate), well known as a product of the Krebs (citric acid) cycle which turns out 36 molecules of ATP at every turn, and is at the heart of metabolic activity in the body. We manufacture 45% of our body weight in ATP every day. This shows how important ATP is to metabolism.

One type of receptor on cell surfaces often uses tyrosine kinase, ie. it attaches high energy bonds to tyrosine amino acids. These are called Receptor Tyrosine Kinases, or Ret.

Ret is made of a very large extracellular protein mass, or N terminal region, which is an immunoglobulin. It crosses the cell membrane with a relatively small (about 40 amino acid) domain, and ends at the intracellular portion, the C terminal region, which does the phosphorylating (kinase activity). The Ret tyrosine kinase is termed RTK.

When a nerve growth factor binds to the extracellular N terminal mass, two RTK’s join (dimer). The RTK dimer then has an affinity for phospholipase C and Src proteins. Then certain adaptor proteins link the activation of RTK to signal transduction pathways, such as the MAPKinase pathway signalling cascade.

Ret has its origin in the Runx1 genes (which are part of the Runt gene family). These genes also play a role in differentiation of neuronal (as well as blood forming) cells into sensory neurons, specially pain neurons (nociceptors). In fetal life Runx1 related activity also determines how deeply the sensory neuron will penetrate into the layers of the spinal cord. The more Runx, the deeper it goes. Runx also affects differentiation of sensory neurons in the dorsal root ganglion (DRG), presumably determining which neurons will act as nociceptors and to what degree of sensitization.

One has to wonder if injury to nerves affects the metabolism and activity of Runx1, a facilitator of nociceptor penetration to the deeper dorsal horn. For example, might injury impair access of incoming pain neurons to the deeper layers of the cord. The deeper layers are where descending, inhibitory interneurons synapse as the pain signal crosses to the opposite side of the cord. Might incoming signal in injured nociceptors preferentially shunt to pathways on the same side of the cord? (eg. the superficial Rexed Layer I, or marginal layer), the superficial ascending pathways being predominantly excitatory rather than inhibitory. It is noted that Runx knockout mice do not develop neuropathic pain easily. (Runx knockin therapy is currently under consideration for treatment of leukemic white cells).

Ret is the receptor for glial cell derived neurotrophic factor (GDNF). Before GDNF can activate Ret, it has to bind to a co-receptor glycosylphosphatidylinositol (GFRalpha) to form a complex. This complex hooks two Rets together, which effects the phosphorylation of kinases, such as MAPK. MAPK is a signal transduction pathway.

Here is another area where research in cancer, which enjoys huge funding, may benefit pain research, which has very little funding.

Because Runx1 (one of the Runt genes) and Ret are important in cancer, especially leukemias or other cancers of blood forming cells, the mechanisms of Runx and Ret manipulation are being vigorously studied. When we can manipulate Runx1, we may be able to eliminate neuropathic pain, as seen in Runx1 knockout mice.

We are not dead in the water on pain. We are just charity cases, hoping for a few crumbs to fall from the tables of the masters. Of course, it could just as easily be the other way around, since more is spent on pain than ANY OTHER MEDICAL CONDITION, but cancer is the biggest baddest boy in town, or is it? Which is the greater evil? Is it death, or intractable pain? One is visible and the other is not, but that does not necessarily answer the question. Nature did not give us an organ to feel the pain of OTHERS, but it did give us the means to perceive OUR OWN pain.

There is an ebb and flow as various clinicians and scientists gain consensus or disagree about which neurologic syndromes or symptoms belong in which category. This is not new in neurology, which is notorious for having many terms, defined differently according to context.

One example is the term, “thalamic pain”. Some modern authors reserve this term for post stroke pain. However, the original authors, Dejerine and Roussy, did no such thing. In Tract Optique, they use the term “thalamic pain” interchangeably with the term, “Pain of Central Origin”. Their co-worker Egger did the same, as did S Weir Mitchell in the United States. Splitting pretends a different mechanism which is far from proven. The nature of the pain after stroke is also often identical to spinal cord injury pain. The difference in distribution (stroke pain tends to be on one side of the body) may or may not justify vouchsafing “thalamic pain” to stroke patients; since, really, they are so similar to post SCI pain subjects.

Similarly, it is nearly universal to use the term “spinothalamic tract pain”. However, there are TWO ST tracts, the anterior and the lateral ST tracts, located at quite different places in the cord. It is arguably sloppy to omit WHICH tract one is referring to, yet it is commonplace to speak of both as if they were ONE tract. This is NOT the best medicine can do. Since discrete injury to one or the other tracts is possible, the patient deserves to know the real story. it also helps researchers in neuroantomy to benefit from reports in the clinical literature if the doctor bothers to make a distinction. We learn more that way.

A recent term is actually VERY good. It expresses things well and we are always on the lookout for any verbal help in expressing the dimensions of neuropathic pain.

Spicher et al in Somatosens Mot Res. 2008 Mar;25(1):77-92. have used the term, “static mechanical allodynia”. Although not likely to be spontaneously expressed by a patient, this new term, or “SMA” as they call it is really very good. It comes to us from the world of PERIPHERAL nerve injury pain research, but anyone with central pain knows just what they are talking about.

“Static” is roughly equivalent to Ron Tasker;s “Spontaneous pain”. In medical terms, “static” means as opposed to “phasic”. We don’t really like either of these terms, because they pretend a dichotomy which may or may not really exist.

“Mechanical” just means in response to mechanical stimuli, as opposed to say heat or chemical stimuli. This matters mainly because at the microscopic level different nociceptor neurons are considered “mechanoreceptors” or “chemoreceptors”, divided into low or high threshold, wide or narrow dynamic range, low or high threshold, etc. Wm Willis Jr has shown that some of these neurons can convert to a different type in hypersensitization, so there is more to be learned. It is not always clear that PhD’s mean the same thing as the clinicians when they publish using these terms.

“Allodynia” of course is our old friend, meaning pain from what ought not to be painful. We have already written here that this term also is ambiguous and has also been applied to such things as “location allodynia” which means pain in an area which ought not to be painful, in response to a localized stimulus. (Use search to read more on Allodynia).

So why do we like the term static mechanical allodynia. It is because the authors make clear that it should be thought of as a paradoxical painful hypo-aesthesia. This is really good. The authors came upon this by discovering that vibration of a painful area caused that area to lose some sensation. They were able to outline which branch of a given nerve was injured by observing which area became less capable of sensing, ie. which area became hypo-aesthetic.

What we like is that the authors have no problem whatsoever using the term “Painful Hypoasthesia”. This sounds like an oxymoron, and that is exactly why it is good. It helps us to express what we have been saying for so long. Yes, it is numb there, but it really hurts.

Spicher even goes so far as to say regarding paradoxically painful hypoesthesia, “the mechanism of pain sensitization is probably central and referred peripherally to the skin by a painful hypoaesthesia.” Read as it is worded, this analysis is really almost humorous, yet it is quite rational.

This statement is a face on the doctors who call central pain patients crazy. They will have to include the authors in their denunciation if they persist in their stubborn refusal to understand that nerves may be too injured to transmit normal touch, but more than adequate as a conduit for really severe pain.

It is interesting that vibration dulls the pain of peripheral nerve injury. We hope more will be done to study this in central pain.