Shaking down another ion channel

Who is the culprit who tortures humans, who does bad things to good people, who reduces mankind to its lowest condition, actually presaging hell, as it were? Pain is the dark side of the force, the diabolical extinguisher of hope and happiness. It was perhaps meant to protect us from injury, but going rogue, it is anything but a friend.  Existing theory points to the ion channels which permit impulses to travel along nerves via what has been called an “action potential”:, which is a sort of current flow achieved by ions of sodium and calcium moving across the nerve membrane.

Just when TRPV1 ion channel was taking all the blame, it turns out that that particular calcium ion channel might have an accomplice. The putative stalking horse goes by the name of TRPA 1 or ankyrin 1.

The transient receptor ion channels are potent activators of pain neurons. While TRPV1 has gotten most of the attention, now studies suggest another channel might well be a co conspirator. In this field, those seeking relief, the disappointed guinea pigs of pain, know not to be overenthusiastic or to start counting our chickens, but at least the new work shows researchers are still investigating. Pain research is not totally dead. Not everyone thinks anticonvulsants are all that a patient in a pain crisis unresponsive to opiates could possibly desire.

Just to make you suitably confused, investigators have reported that a new drug, ADM-09, results in “calcium-mediated binding of the carnosine residue and disulphide-bridge-forming of the lipoic acid residue accounts for the observed persistent blocking or TRPA1. Feel better? Okay, not yet, but somehow just knowing the whole business of basic pain research has not gone away entirely, that scientific gobbledygook can help keep the spirits up. That phraseology just used to snow you actually means  ADM_09 is an effective antagonist of the nociceptive sensor channel..”

Or, in other words, if we could block TRPA-1 we might be able to block pain.

This was reported in:

Sci Rep. 2013;3:2005. doi: 10.1038/srep02005.

A TRPA1 antagonist reverts oxaliplatin-induced neuropathic pain.

We listed all their names so if they read this they will know we have put aside our agony long enough to appreciate the very hard work they are doing. The Central Pain patient may not be the best to discuss his suffering in terms others can understand but he likes to think he might be able to express gratitude..
Note to researchers:
If you cure this you will definitely win the Nobel Prize and make a billion dollars. And generations of Central Pain families will name their children after you. If you had any idea how unpleasant it can be to deal with someone with Central Pain, you would take mercy on those families who have to deal with it by making the CP go away. In the meantime, thanks for trying to turn down the flame on the most severe pain state known to man.

TRAUMATIC STRESS DISORDER, PAST AND PRESENT

TRAUMATIC STRESS DISORDER AND PAIN

 

Hmmm. Something is wrong. A word is missing somewhere. Oh, there we go. The word POST is missing. POST traumatic stress disorder. According to the language, stress disorder is something the body and brain develop AFTER the stress. Apparently, during  the stress, the mind has blanket immunity to such problems. But does it really? Do our everyday experiences confirm that during a robbery, tornado, assault, etc. that our emotions are held in check, our thoughts and feelings sturdy and true, while only later does the system collapse and become dysfunctional? Is that right?

On second thought, maybe there is a larger category of which POST TRAUMATIC STRESS is a subtype. Maybe DURING the catastrophic event, we can go all wobbly and confused and frantic. Maybe some kind of hysteria can overtake us when we are actually IN the throes of a crisis, DURING the dreadful event. How long does the PRESENT last. Is it a couple of minutes, an hour, a month or even longer. How about a lifetime. WHEN exactly does the system give out and a STRESS DISORDER set in? What do we call it if we never get out of the pain in order to develop PTSD.

Take for example, CENTRAL PAIN. Does the frantic nature of severe pain somehow have a protective feature, an adrenaline rush perhaps, which shields us from the impending shutdown? If so, how much adrenaline can we count on? Does it last years?

Dr. Ron Tasker, the famous neurosurgeon who discovered that pain in the body is carried in the spinothalamic tract, has indicated that fully elaborated central pain is the most severe pain state known to man. If he is even close to being correct, and no one has more experience with pain patients, then did anybody else notice this? Well, S. Weir Mitchell, the civil war surgeon, was amazed to find his most brave officer reduced to the “TEMPERAMENT OF THE MOST NERVOUS GIRL” as soon as Central Pain set in after a bullet to the neck injured the spinal cord.

The Civil War being notably brutal and gory, things had to have been pretty bad to attract the attention of someone who had seen it all. What exactly was going on? It must have been impressive, because after treating some more Central Pain patients, Dr. Mitchell convinced Johns Hopkins Hospital to set up an entire wing for nerve injury pain patients.

Was their treatment for POST traumatic stress or was it something different because their pain was ongoing. They were actually IN PAIN, still, so one could not very well term it POST traumatic since the pain trauma was still there. Imagine, an entire ward at a top hospital full of formerly brave soldiers, acting like the MOST NERVOUS GIRLS. This was not over their paralysis, but their pain. What is up with that?

Aside from the offensive to feminist aspect of Mitchell’s choice of words, we get the picture. They were not themselves. They were different from those charging into the cannon’s mouth. They had left part of themselves on the battlefield the day they were injured. They were in fact living a life of deaths. Their real personality was no more.

Was this worse than post traumatic stress, this intratraumatic stress? Was it less? Or did it have components of two different disorders? Is chronic PAIN really identical to post traumatic stress? Can we help one but not the other?

When Riddoch, who invented the term “Central Pain” gave his report in the Lancet, he called the condition,  “A Pain Beyond Pain”. What could possibly have led him to characterize it this way? What was he talking about? There is nothing beyond pain, or is there?

These are the questions we ask. The psychiatrists and psychologists literally descend en masse on those with post traumatic stress, but they are conspicuously absent in the pain clinics. Is Central Pain too mysterious even for the psychiatrists? Does this mean the mind stays on even keel until AFTER pain has gone, at which time it flips out. Are psychiatrists only able to deal with incidents AFTER THE FACT, or can they be of assistance DURING a terrible trauma, even a long lasting one? Especially a long lasting one. Are the stresses and appalling shocks suffered by the patient’s family too remote and inaccessible even to study, much less treat? Does the condition even have a name? Is that out of reach? What are they waiting for?

Or are we assured that the human mind is durable and that the CP subject (who himself regards his pain condition as WORSE THAN THE PARALYSIS) will need no help beyond what opiates can provide during the months and years during which he is taken apart minute by minute, day by day, by an illness too terrible to describe.

If you relate to this quandary, and feel you could use some help now, you are obviously just“ a nervous girl” UNLESS, of course, the condition of pain present is really something sinister, and indescribably awful. Were the Civil War soldiers right that the pain is worse than the paralysis? Hmmm. That would make it pretty bad, now that you think about it..

 

NOTE: Due to the relentless intrusion by internet trolls, the comments function has been shut off. Please send any comments to nihbay@yahoo.com

Doctors and Patients are Talking Past Each Other

Why isn’ t Central Pain any better understood now than ten years ago?

On one occasion a neighbor took her sick child to the Pediatrician for an antibiotic. He told her the illness was viral and that not wanting to contribute to antibiotic resistant strains he would not give an antibiotic. He said to just keep her away from other children and the illness would have to run its course, since nothing helps viral colds. She was entirely outraged because the doctor charged the usual office fee for the visit, but did not do anything. She still had a sick child. Patients do not like to be charged for being told nothing can be done.

 

Is there anything like this in Central Pain? Absolutely. There is no satisfactory treatment, according to the National Institutes of Health. While treatments are alleged for peripheral nerve injury pain, no study has shown this to be the case for CENTRAL NEUROPATHIC PAIN. The doctor knows this but may send the patient home on successive visits with any number of drugs designed for peripheral nerve injury pain. A sedative may help a bit, but basically, the patient must learn to manage life to minimize pain because there is as yet no real treatment for the condition.

 

The doctor, knowing that no treatment is forthcoming if it is CP is not likely to press the patient to stop talking gibberish about Central Pain (what else can one do if there are no words for dysesthetic pain) and try to come up with something like an adequate verbal descriptor.  The patient is in PAIN and wants the doctor to do something right NOW.What else would a compassionate doctor do?

 

Until patients are required to be more specific, the doctor will be poor at sorting out Central Pain from other pains. Until the doctor has something real to offer, the patient will not want to pay money just to expand the database of the doctor’s knowledge. Almost invariably, the patient wants to talk about pain severity and not pain quality, because they want relief. And so, no progress is made. Only when both patient and doctor determine to do it right and take the time for a real history and physical will any of this change. In the meantime, with limited time provided by managed care, things will stay the same, with ignorance for the doctor and disillusionment for the patient. A real workup must be thought of in terms of hours or days, not minutes. Third party payers will have to do their part if things are going to move forward.

Personal Experience of Central Pain

A CONTRIBUTION FROM A SUBJECT WITH CENTRAL PAIN.

It is with some reluctance I commit this to writing. Fifteen years ago I would dismiss me as mad.

As someone who never minded pain, I am utterly and profoundly humbled, and as you know deal daily with suicidal ideations.

I have no confidence in Prialt but it is the last stop so head into it with open eyes and an eye on what is happening to me, and undergo cognitive evaluations weekly through 2 personal friends who are shrinks.

I have taken several days that I might review, edit out exagerations due to immediate circumstance and to be sure to try to include all.

I am (was) intelligent and have a science (EE and Physics) background in addition to the Intelligence work and as a scientist I cannot reconcile any of this other than a total malfunction of a complex system with cascading events and triggers.

Upon reading it seem the histrionics of insanity, but having walked away from narcotics and virtually every medication I could tolerate without extreme side effects as they have had NO effect what so ever, I can categorize myself as either insane or this is real, and most unfortunately this is real.

Apologies again and I hope this may help someone somehow.

____________________________________

N.B. At this point we insert a sidebar to assist in understanding the remainder of this person’s description:

This is a submission from a person with central pain. It reminds us of the severity of the condition.

Note that this person has both spontaneous (constant) and evoked (elicited usually by light touch or temperature change, but sometimes the evoking stimulus cannot be identified) Your doctor should be made aware of which pains are continual or ominipresent, which can be evoked, and which are spontaneously intermittent.

Some of the central pains convey discriminative information (location, nature etc) while others are too vague to describe. There is no vernacular and not even any adequate clinical vocabulary for central pain dysesthetic burning, so the person typically borrows from the language of ordinary pain or invents terms. This borrowing makes the listener THINK they understand, but the dysesthesias are not like any other sensation. By comparison, a mix of blue and yellow can produce green color, but green color is not adequately described by saying well, it is blue and it is green. MIXES need a new name. Unfortunately, the name given to the mix of central pain burning is dysesthesia, a vague term if there ever was one.

The clinician can gain a little understanding of Central Pain by injecting themselves under the skin with capsaicin, which hits the TRPV1 receptors, (known to be related to thermal sensation) but dysesthesia is a MIX of sensations, which mixed together yield something which no human experiences, unless there is central pain.

Acid is painful. This is not rocket science. Painonline was one of the first to propose that the metabolites of eicosanoids, ie fatty acids derived from Omega 3 fats, were behind central pain. Further research has shown that the specific fatty acids are derivatives of linoleic acid. When these are oxidized, they become highly irritating to pain nerves, particularly those associated with thermal sensation.

Acids cause a burning sensation. This burning sensation can be and is perceived in central pain in a heightened fashion. The core sensation of central pain has long been described as a burning, “LIKE ACID under the skin”. The primary acids involved are called oxidized linoleic acid metabolites. The two more prominent are 9-HODE and 13 HODE. This neuroacidity is known as neuroinflammation.

Now that some understanding of the pathophysiology is known, clinicians should stop acting confused about what the central pain patient is saying. He is saying that he is being burned as if acid were under the skin, which really means in the nerves which lie just under the skin.

Why this burning can get to the brain is probably NOT related to normal nerve transmission. It may be a chemical chain reaction whereby acid production under the skin CHEMICALLY induces a similar acidity in second and third order neurons, EVEN IF those nerves are incapable of reaching the brain with normal sensory messages. We find the acids in the synapse at each level. We also find the glia which surround neurons multiplying and driving the acid production via growth factors, such as brain derived neurotrophic factor (BDNF) in what seems to be related to some sort of attempted repair function.

While this terminology is a bit mysterious to the average public, fatty acid metabolism is part and parcel of the biochemical education of EVERY physician. Why it has taken them this long to begin to put pieces of the puzzle together is almost certainly related to the fact physicians have assumed they know pain, and what the CP patient is saying does not match. Hence, many have relegated it to something like back pain, or even some form of malingering. Central Pain is way more severe than ordinary neuropathy. This real severity nevertheless has sometimes been attributed to some sort of weakness or even drug seeking on the part of Central Pain patients. After all, the Central Pain patient has nothing visible going on, so surely they must be exaggerating, goes the mistaken presumption. There is plenty going on, but fatty acids are not visible to the eye.

Patients with central pain need extensive personal and family counseling as well as whatever medical care can be provided, which is limited since conventional pain meds seem to have little or no effect on this type of nerve injury pain.

S. Weir Mitchell, who first described pain of central origin during the Civil War, marveled that his bravest captain was struck in the neck with a ball and that the resulting burning to light touch was so severe that it reduced him to the disposition of the “most nervous girl”. This person is emotionally wrought and his words might remind us of Mitchell’s description of his formerly brave captain.

For your own sake in description and to help educate our caregivers, it is helpful to categorize your central pains into specific groups. The following guidelines may be used.

DYSESTHETIC PAINS

Dr. David Bowsher described these as bizarre burning pains combined with a paradoxical component of COLD. This definition is more easily elicited from those who have recently acquired central pain, since with time, the sensation simply IS, and it is rather amorphous, except as to the burning.

As in all verbal choices aimed at central pain, even Dr. Bowsher’s words are an approximation. The essential aspect of dysesthetic pains is that they are unlike what would be experienced in normal pain. The subject has NEVER felt the dysesthetic sensations prior to acquiring central pain. The only thing that can approximate any dysesthetic sensation is the injection of capsaicin under the skin, and even there it reaches only the burning component and does not evoke the other dysesthetic sensations.

The proposed reason is that pain, which normally is highly discriminated, conveying a very large amount of information to the brain, presumably because pain is necessary to prevent further injury. This system is deranged with the dis-integration of signal in nerve injury, so that a MIX of sensations, unfamiliar in nature, results. We call this mix dysesthetic, but the most prominent aspect of it is most frequently described as having thermal qualities, “like acid just under the skin” (Note that this author uses similar terminology”)

Despite the predominant burning, one must also consider what it is that elicits or exacerbates the pain. Elicitations of greater pain through various stimuli are called “EVOCATIONS” and these are nearly always said to be blasts of cold air, also light touch, particularly occlusive light touch (such as laying a newspaper across the skin.

Mitchell’s test is to use light touch on a burning area. If the pain is from injury to the PERIPHERAL nervous system, the evoked pain will be instantaneous. In pain of CENTRAL origin, ie Central Pain, there is a slight latency, sometimes of only a few seconds, but typically around twenty seconds before the evocation really gets going.

Carl Saab, from UT and Yale, has elsewhere at painonline contributed an article on his research that confirms this same CP latency in the roof nuclei of the cerebellum (the vermis). Oddly, many pain specialists seem unaware of this simple test. It is not clear whether the current tendency to lump central pain with peripheral neuropathic pain is due to mental laziness in learning the clinical patterns, or whether the caregivers simply cannot sort out and understand the confusing verbal descriptors which patients use, often combining their central pain with the musculoskeletal (normal) pain from the original injury and surgical alteration of the motion segments of the spine. It raises the question of whether Central Pain is not really knowable to anyone who does not have it.

However, we lament the failure by many to differentiate the two conditions, since fully elaborated Central Pain is terrible and well beyond the impact of peripheral nerve injury in one limited area. (All pain is bad and so peripheral neuropathy is not to be denigrated by making this statement–if nothing else the AREA of Central Pain is typically large, while peripheral neuropathy is usually in smaller areas, cf. the impact of small burns to large burned areas).  Certainly if the clinician begins mentally to regard and treat central pain in the same fashion as vastly less severe diabetic neuropathy, the patient is not well served. The DSM book, by the American Psychiatric Association classifies mental disorders, but still impacts how pain is viewed generally.

There are rumors the upcoming DSM5 diagnostic edition may lump all nerve injury pain into one category. If this is true, we expect to see them differentiated once again in the future as more is learned about the two separate conditions. Recent research suggests that BOTH Central Pain and Peripheral Neuropathy result in upregulation of TRPV1 receptors, but these are also upregulated in response to ordinary painful heat, so this is clearly not the whole story of Central Pain.

LANCINATING PAINS.

Like normal pain, these pains convey discriminative information, such as distinct location, radiation etc. and they feel like normal pain. This author refers to these pains as “electric pains”.

MUSCLE PAINS

In the literature these have been differentiated into kinesthetic dysesthesia (bizarre burning pains associated with movement of muscle loading) and isometric dysesthesia (pains not associated with movement, also sometimes compared to confinement cramps). It has been theorized that muscle pains result from dysfunction of the gamma motor system, which is part of the muscle spindle, as it passes to the brain.

Any normal musculoskeletal pain such as could be expected from vertebro/ligamentous injury or surgical changes in the motion segments of the spinal apparatus are NOT to be included in this category.  Dysesthetic kinesthesia can be severe and the literature contain reports of patients who are either totally or nearly paralyzed by such pains even though they have an intact motor unit. The majority of such patients are incomplete quadriparetics, it would appear.

___________________________________

Personal Central Pain Description continued

I am almost embarrassed to write this and do so upon request, that others may learn something. I would not believe this if someone had told this to me before I had it, and with decades of martial art and competitive fighting, pain has historically been an inconvenience and manageable. I cry from pain several times daily, leaks out, again embarrassing.

Relevant History
Personal: Competitive Full contact fighter Martial Arts, Multiple Black Belts several disciplines, Football, Wrestling, Powerlifting, Combat veteran

Fused C2-3 unknown origin possible congenital, possible minor fracture fused while healing
Laminectomy T ? between shoulder blades
FusedL3-4-5,
Advanced Degenerative Disc Disease L1-2 very advanced
Spinal Stenosis, some areas worse than others

Chronic continual spasms nipples down, IT baclofen pump inserted Oct 2012
Boston Scientific Dorsal Spinal Stim Paddle leads inserted top down ~ T6, Totally ineffective, contributed to spasms out of operation for ~ 7 years, remains in place

I will attempt to describe location, frequency, intensity, type/sensation.
In all cases where temperature is cited for causality, cold is much worse than heat
In all cases where touch is cited for causality light touch is more likely to evoke the highest pain response, while stronger touch is more likely to evoke spasm attacks.

Pain is from nipples down.

Nipples through Abdomen front, approximately 80% of the time, aching indeterminate origin cannot pinpoint exact location, no causality,

occasional burning, frequent pins and needles moderate severity, unknown causality, can be
evoked by change in temperature, brushing of clothing, manageable typically 5-6 on pain scale
Spasms from severe to “vibrating pulsing” currently severity has been reduced with IT Baclofen

Back from C down to navel region in an inverted Russian cross, the major cross at the lumbar, the minor across my shoulder blades 100% of the time, no known causality cannot evoke
Spinal column pain 5-10 feels arthritic in nature along spinal column severe ache pain 8-10, and severe sharp lancinating pain
approximately 4-6 inches across again impossible to identify exact place seems approximately ¼ – ½ inch below the skin but not in the spinal column, severe ache 7-9
electric shocks, daily and frequently 9-10, sear directly down the spinal column/cord often right
down to toes but start high T .
Lancinating jolts (like being shot based on personal experience) pain 9-10
These are more prominent from low T down
Burning, Pins and needles 5-8, unknown causality can be evoked by heat, cold, rough clothing
Subject to severe spasm despite baclofen, although baclofen has helped

Navel region down bi laterally sometimes a bit worse on right side, right may be a 10 pain level left only 8-9 just enough less to differentiate

Acid dip,like being dipped in battery acid where it slowly and horribly burns through the skin until neutralized by a high PH application after which while no longer physically burning
It feels it is, one of the very worst but fortunately only 4-5 times a week

Electric shocks, daily and frequently 9-10, sear directly down the sciatic, peroneal often right
down to toes but start high

Lancinating jolts (like being shot based on personal experience) pain 9-10
These are more prominent from low T down

Crawling fire ants 100% of the time 8-10
Pins and needles severe 100% of the time 8-10
Burning, severe 8-10 100% of the time, if only an 8 putting on pants or a breeze or sitting or
touching evoke full response to 10.

Around house wear only boxers or extremely loose soft pajama bottoms whether inside or outNerves, seems like the entire Sciatic nerve is being ripped out of me from my big toe through mylumbar. Stretching to breaking point pain 9-10 Red hot and covered with shards of glass, in

addition to being pulled out, being twisted around and around. Agonizing, bi-laterally near
continual

Pain Shell (my description) an envelope of pain ~ ¼ -1/2 inch below the skin envelops me from foot to
groin excruciating agony, vomit, experience sensory disorientation. Cannot distinguish conversation vision blurs, tunnel no visual discrimination unaware of surroundings lose timeline observers indicate these episodes last from 15 minutes to several hours,

Residual pain feels like I have been physically beaten and remains for days. [see kinesthetic dysesthesia above] This may be the very worst, were it possible I would likely commit suicide during these. Pain 13 on a 1-10 scale.unimaginable, indescribable, I scream sometimes til my throat bleeds (I am unaware of this) scares anyone who has seen it, Pain doc only observed something similar in a thalmic stroke victim who suicide out, feet move to a Babinski pose, not a hard spasm can be pushed back to normal (painful) but then moves back to the previous position. When this happens it always includes all of the other described
phenomena

Leg Sensation. On the rare low pain day 6-7 my legs and leg muscles feel like they are filled with hot bubbling seltzer water. [see kinesthetic dysesthesia above]

Legs subject to severe spasms daily despite baclofen (although reduced from pre IT Pump)

Penis feels like it is being squeezed/crushed sometimes or bursting from the inside out at others

Left testicle aches throbs and vibrates (not actually vibrate but has that sensation) near continual, pain level low but very annoying maybe 4-6

Frenum extreme pain, unknown causality, 20-30 times a week time ranges from minutes to a day. Again hard to “locate” exactly but the frenum is not that big

Perenium extreme pain, typically evoked by bowel movement 8-10. Lasts minutes to hours

Butt feels like a drill is being driven through my ass bones (where I sit, the nerve plexus there) always there sitting exacerbates it always 8-10

no anal pain, occasional burning

Feet, stepping on a nearly imperceptible pebble will evoke severe local pain 3-10 minutes later that lasts for hours

Observations
Much of the pain cannot be precisely pinpointed, bizarre to me but…
EMG tests invalidate diabetic neuropathy (extremely well controlled insulin dependent diabetic. Only 1 A1C in excess of 6 in more than 16-17 years)
Recent extensive neuro workup for any organic complications, none indicated

Zero pain relief from anything, tried the anti-anxiety, every narcotic, marijuana, Ma (oriental) Meditation (still practice it), acupuncture.

Baclofen has helped a great deal with spasms and pain associated with the spasms themselves, except the extreme ones. prior to the IT baclofen running a finger lightly up the back of my leg caused severe spasms, lifting my foot backwards had same effect, crawling backward had same effect etc. All spasms reduced in frequency by 50% minor spasms have markedly reduced severity; the “screamers” are unchanged

HOUSE DOES IT AGAIN.

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, only 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 with the scale.

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, so that 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.

Who are you? Oh, it's me.

Here we reprise the earlier article, “Insane in the Membrane”.

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.”

Dark Pain

Dark Pain.

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.

Central Pain press release from the Univ. of Maryland

 

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.”

Breakthrough in Central Pain Understanding

Painonline has at times been hardpressed to explain why central pain patients have so much muscle pain.  Both kinesthetic dysesthesia (pain with muscle loading) and confinement cramps, aka isometric dysesthesia (the largely spontaneous sensation of cramps in the muscles) are exceedingly common in central pain. Although often glossed over because the patient complains of such agony from burning sensation on the skin, as Beric has pointed out, the muscle pains may be so severe that a person with an intact motor unit may be functionally paralyzed. Muscle pains have been the stepchild of CP.

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.

 

 

Cold Fire and the Thalamus

                                                    

 

            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.

 

 

This information and the resaons for it follow in a review of  the remarkable article,

 

Davidson S, Zhang X, Khasabov SG, Simone DA, Giesler GJ JrJ Neurophysiol. 2008 Oct;100(4):2026-37.

Termination zones of functionally characterized spinothalamic tract neurons within the primate posterior thalamus.

 

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.