PainOnline.com

The Intralaminar and Ventrobasal Thalamus

If the name of this webpage does not turn you off, you are indeed determined to learn more about central pain. It asks, strangely enough, the self-contradictory question of whether pain is a sensory or a motor function, or whether it matters. At the very least, we hope it will enlighten the clinicians who are still unaware that muscle pain is very, very common in CP.

As alluded to in some of the other technical web pages, all brain science rests on certain assumptions, some of which are being updated even as you read this. All conclusions are transitory and scientists continue to find the unexpected all the time.

It is too bad the public does not share this fascination with our brains. Perhaps we could compete more effectively for funding if we could show the central position in brain science which CP occupies by virtue of its dominance of the thalamus. All that is necessary to become fascinated with astronomy is the eye, but to become fascinated with brain science requires education.

Once you get started, the brain is amazing. Even Francis Crick, the codiscoverer of the DNA double helix, who has been kind enough to offer helpful correspondence to us on the role of the insular cortex in the "painfulness of pain", famous already in genetics, found brain science so fascinating he switched to this field. For his input we are grateful.

The thalamus sits right in the center of the brain. Actually there are two of them, one on each side, each about 2-3 centimeters in length, shaped like a short pontoon or rounded pod. The thalamus is now believed to write on the fly ALL of the driver software that continually flows to the cortex. One thalamic researcher joked he had discovered we are "pod" people.

A layer or laminae runs down the middle of the thalamus lengthwise and develops bulges twice to encircle the small "intralaminar nuclei". A nucleus is a collection of cell bodies, whose neurons are devoted to a particular task.

To the side and below the intralaminar nuclei are the ventrobasal nuclei, which include the very important ventroposterolateral (VPL or body pain center) and the ventroposteromedial (VPM or face pain center). (The connections with the VPL/VPM from the cerebellum may well have to do with pain inhibition, in light of the work of Carl Saab, whose article appears elsewhere at this site.) The VPL is where fibers from the spinothalamic tracts terminate, which we mention elsewhere. The spinothalamic tracts carry pain up through the cord to the thalamus. If the thalamus were a sled, the VPl and VPM are located about where the middle of the runners would be.

The intralaminar nuclei are located where the line running lengthwise down the middle of the sled would be placed for decoration. To be comparable, this line should bulge once in the middle and then flare out like a "Y" at the front end, where we would find the anterior nucleus, which processes virtually ALL messages returning to the body from the cortex. These facts place the thalamus at control center.

You may go to the library to read about the intralaminar nuclei, in a neuroanatomy text, or you may wish to consult painonline.org, which has a more extensive discussion of thalamic anatomy.

Complex chemical pathways converge at the VPL and VPM, including some from the cerebellum. Dr. Carl Saab of Yale has only recently discovered a role for the midline roof nuclei of the cerebellum in pain inhibition. Prior to his important work, it was not known that the cerebellum, a motor coordinating center sitting low and behind the main brain, was an active force in pain inhibition. Scientists are still trying to get over the shock and struggling to understand how the sensory aspect we call pain is neurologically hooked to motor function in the body. Open stimulation of the motor cortex has been shown to suppress Central Pain. Immediately behind the motor cortex which resides in the front of a groove running transversely across the brain, is SI. SI is the primary sensory area and receives input regarding phasic pain (an example would be a blow to the body).

Tonic pain is processed further back in SII, in the parietal cortex and in the insular cortex. An example of tonic pain would be a constant pinch. Since chronic pain is constant, we would expect SII to have a role in Central Pain and indeed it does. Recent functional MRI has also shown activity in the insular cortex, an infolded part of the sides of the brain, around which the other lobes grow. Dr. Francis Crick has indicated to me that the insula is that part which informs us that "pain is painful". There is recent confirmation of this in brain imaging studies. The frontal cortex and the cingulate cortex are thought to create the emotional affect which can accompany pain.

The thalamus is a two way control center. It receives sensory input FROM the body and distributes information from the cortex TO the body. The input comes in a train of action potentials, or voltage spikes, which create a frequency modulated signal (ie. the frequency of firing determines strength of signal). This input has undergone excitation and inhibition all the way to the thalamus as other pathways have their say, but this is nothing compared to the processing going on in the thalamus, which must digest the input, and write driver software for the cortex, virtually instantaneously, to travel with the signal to the conscious brain, or not, as the thalamus chooses. As mentioned there are two sides to a signal, the excitatory and the inhibitory. Signals which stimulate Glutamate tend to be excitatory, and signals which stimulate GABA tend to be inhibitory. Either way, it is the action potential which carries the message.

If your eyes saw current and you were very small and standing at the nerve cell membrane, you would see a voltage rise like a sine wave moving along the nerve. This represents sodium ionic flow into the neuron through pores, which are called channels. As the sine wave falls, it rises again to reflect potassium flow. The action potential does not take place unless other ions, such as calcium and chloride contribute. How these other ions contribute can actually reverse the resulting signal. If a nerve cell is damaged, it cannot produce KCC2, which is a protein which carries the chloride to the cell membrane. When this fails, the "priming" for the action potential fails, and any inhibitory signal will be converted to an excitatory signal. This is what prevents the brain from shutting off pain in Central Pain.

Ion channels, the little bent tubes through which the ions flow, are manufactured by the cell. Not surprisingly, when the cell is damaged, the ion channels are not produced normally. This goes to the excitation phase. The ion channels are numbered and they are known to open when the voltage difference between inside and outside reaches a certain level in millivolts. In adults, the Nav1.7, Nav 1.8, and Nav 1.9 are normally the major players. In Central Pain, something happens to stop production of these channels and one which normally only appears in infants, when growth factors are developing the body, is wildly overproduced. This channel is the Nav 1.3 channel and it causes too much excitation of pain. The nerve is so sensitive that it fires even when there is no injury occurring to the body. We call this Central Pain, and of course, you already know it is a double whammy, since the lack of KCC2 means efforts by the brain to shut off the pain, and quiet the nerve, is turned into more pain. Central Pain can be very severe, as a result. It puts the pain system between a rock and a hard place. Too much Nav1.3 and too little KCC2 is a knockout punch. The thalamus interprets the signal as it receives it and passes it up to the boss, the brain.

Even the boss has a boss. The thalamus and cortex take turns bossing each other. Nothing comes down from the brain without passing through the anterior nucleus of the thalamus, but the anterior nucelus is not even the most important nucleus of the thalamus. If you were of the proper size and could hear the thalamus, it would seem like you were sitting next to powerful generators in an electricity generating plant. There would be throbbing hums which sounded impressive, but you would not be sure what they meant. Some think they mean a cycle has occured; ie., input has arrived and software has been created and assigned to deal with the input and the processed input has been sent via thalamo-cortical pathways (thalamus to cortex) to the Vth layer of the cerebral cortex, from where resulting signals may span out and be distributed to other layers and locations for intrabrain connections, called cortico-cortical pathways (ie. brain to brain).

The main sensory and pain area is SSI which is right behind the groove which traverses the center of the brain from side to side. Further back behind SSI are the paired parietal lobes, where the second pain area, or SSII is located. Central Pain has been linked to brain lesions, or even seizure activity, in SSI and also in SSII. In the brain SSI stands for "somatosensory area I". The thalamus can be thought of as the master software writer, operating with blinding speed to write driver software almost instantaneously, which the cortex can use to process signal. Biological computers run chemically, and Central Pain is a malfunction of the chemical processes in the thalamus, probably due to the presence of too much acid. We are greatly oversimplifying here.

Rhythmic signals pulse through the thalamic nuclei. A nucleus as used in neuroscience means a concentration of similar cell bodies. The frequency of these rhythms almost certainly indicates what is going on, but we are not smart enough yet to read clearly what these frequencies mean. We have not cracked the thalamic code.

Some of the pulsing frequencies are called "oscillations" as they seem to ebb and flow in a pattern. Central Pain has been linked to a 0.2-0.4 Hz frequency signal in the VPM and VPL nuclei of the thalamus. This is very slow and was missed for a long time. Oscillations at other frequencies have been known to exist for quite a while. Somewhere in the brain, there is probably a template to match the input patterns and interpret the results in terms of matching to the template. One theory of CP is that when input does not match what the template knows is normal, a pain message is generated. There is some evidence that a pain template is formed even before birth and then elaborated in early life. We may well inherit our sensitivity to pain.

The main outdated assumption of brain science is that a neuron or nerve cell is capable of truly DISCRETE, ONE-DIMENSIONAL function. The thousands of synapses (connections) which impact on each neuron have put this idea to rest, since those connections control the neuron, and come from an amazingly diverse number of locations. Learning is thought to be a process of "synapse strenghtening".

Synapse summation means a nerve cell firing pattern looks more like a bell shaped curve on an oscilloscope than a single vertical line. At the functioning level, neuron patterns are NOT particularly quantal, ie. made of predictable events, they are more like bunches of statistical likelihood, or brain probabilities. It is probable that a pain neuron will do a certain thing, but those synaptic connections may say otherwise.

A pain cell may be overwhelmed by the desire to score a touchdown or dodge a bullet. On the otherhand, when CP so directs, the "NO PAIN" signal may be turned into a "LOTS OF PAIN" signal by input from various sources. Some cells do nothing but regulate other cells, and act more or less as controllers, giving "orders from headquarters". These neurons are called "interneurons", and the pain signal passes through many of them on the way to the cortex.

The interneurons may be obscure, but they are potent. They can turn night into day or day into night. Interneuron science is in its infancy, but there appears to be almost no limits to their influence, nor to the influence of glial cells which surround neurons and influence the signal along its entire course to the brain.

The brain is not like a football game, where we want the referees to mostly stay out of the way and let the players do their thing. In the brain, it is a group of referees which only occasionally pay much attention to the players. The brain is like a bunch of lawyers which must be kept quiet so one thought at a time can proceed, if permitted. The thalamus is like a judge, deciding what the lawyers can and cannot say out loud.

Evidence for this comes from the microelectrodes which are inserted into nerve fibers which have been threaded out anatomically in lab animals. A stimulus is applied and a response is measured higher up in the nerve fiber, or even along a neuron which is upstream but which has connections to the neuron in question.

The idea of discrete pathways was for many years the majority, conventional viewpoint. Unless your doctor is following the literature, it will almost certainly still be his/her point of view and this will make it hard to accept your bizarre story of mixed or substituted pains ("cenesthetic" pain, eg. cold air causes the skin to burn) and they may be completely unaware of the marked muscle sensations in many central pain patients. Central Pain itself is a substitution for the very slight sensation which continually comes up through the sensory apparatus from just beneath our skin. All the input is integrated into a signal of well being, which is mostly ignored by the preoccupied mind.

Loss of integration in CP makes perfect sense to those who study integration of the various brain signals, but it makes no sense to those who have not studied integration of input by the thalamus.

There is constantly a level of noise in all nerve tracts, caused by the kinetic energy of heat, moving charged ions across membranes, which causes certain neurons to bounce over the threshold for firing an action potential, or voltage signal propagated in the nervous system. Don't believe anyone who tells you you only use five percent of your brain. ALL neurons are firing at some frequency ALL the time, giving usable information even in the chaos. The noise is tremendous, but you are nevertheless able to speak or think one thing at a time because the brain somehow brings order out of chaos and hears through the noise. The thalamus plays this role and also decides which message should go to and come from the cortex (the gray matter on the brain surface).

The thalamus appears to write software to facilitate its decisions instantaneously, which then determines how the cortex will handle the thalamic signal. How's that for coding driver software? Our brains are not as fast as the big supercomputers on calculations but we can turn out the software in nothing flat.

Notions of the pain system as a system of line wired tracts simply cannot stand up to scrutiny any longer. That old view is at least 20 years out of date. It had too many inconsistencies. In many areas of the thalamus the majority of pain fibers passing by are not the mainstream pain “tracts”, either numerically or functionally, and may be sharing chemicals more than they are sharing direct electrical signals. The most important neurons in the cord are the above mentioned “interneurons, which interpose themselves between the first order neuron coming from the body surface and the second order neuron going up the cord. Interneurons are controlled from above. The brain does not like to be cut off from the environment. It can upregulate the function of the interneurons any time it wishes, and if these interneurons are connected to pain fibers, "Look out Lucy!"

The interneurons are probably more important in the pain process than the main signal and are certainly more numerous, yet we know almost nothing about them. It is like saying we know what a college is like by interviewing three or four students. Many, if not most interneurons, are inhibitory. Whether they remain inhibitory in Central Pain is open to doubt. The cord itself and the brain cannot detect pain, yet in Central Pain, they can. The pain tracts follow their master, the thalamus. A simple alteration in the thalamus should be capable of recruiting any signal into the pain process by protein production which increases nerve acidosis, or changes the protein folding and conformational changes in the ion channels of connecting neurons. Toxins or venom usually work by blocking ion channels and some of the chemicals pouring out in central pain behave more like venom than simple neurotransmitters.

Blockage of inhibition or increased kinase activation of exciters is sufficient to induce very serious pain in the unfortunate individual who suffers it.

EXCITERS WHICH EXCITE INHIBITORY PATHWAYS EQUALS INHIBITION.

Assumption that the cord and brain react the same to exciter chemicals led to many of the errors of the past. In the brain, exciter chemicals which stimulate inhibition are often erroneously termed "excitatory" neurotransmitters, but in reality "Pretty IS as pretty DOES". Morphine and other opioids are examples of this (see below). Unjustified assumptions have been made when identifying an excitatory chemical, such as glutamate, that the tract is an excitatory one, but what has really been going on is excitation of inhibition. In other words, excitatory chemicals can lead to inhibition of pain signal.

Similarly, the discovery of GABA, an inhibitory chemical, or of endogenous opiates, which are supposed to be decreasing pain, may in fact be inhibiting inhibition (so called “disinhibition”). Thus, the whole science of chemoarchitecture of the central nervous system is undergoing reexamination. Most controversial of all, but with considerable evidence to support it, is the debate of how two nearby neurons influence each other. The work of Marshall Devor indicates that neurons are extroverts, definite people persons, who exert strong social pressure on each other when injury to one occurs. (termed "crossed afterdischarge")

The easy assumption would be that two interposed neurons communicate along their paths and excitation in one stimulates and enlists firing in uninjured neighbor neurons. However, the studies of capsaicin injection indicate that the good neighbor mechanism described above, if present, is almost surely secondary to the major means of excitation, which takes place up high, where the two nerves interact in the cord area.

For example, if capsaicin, (extract of red peppers) is injected under the skin, there is sensitivity in the area of injection. However, outside the area of injection is what is called “secondary hypersensitization”. Big, thick, A beta fibers yield a burning sensation where no material was injected. How did an expanded zone of burning occur) The capsaicin is not spreading to neighboring A beta pain cells (the big fast pain fibers) locally. What is happening is that one or two small C fibers in the area of injection are traveling to the cord, interacting with interneurons which can upregulate the impact of firing in the A betas, making them hypersensitive and recruiting others to fire at the cord level witht the result that ANY firing, even simple touch, is magnified into pain.

A similar process probably also occurs in the thalamus, where the second order neuron arrives in the brain, but almost nothing is known about such mechanisms in the thalamus. However, the chemicals which could produce it have been identified in the thalamus, such as interleukin 1-B-alpha.

Furthermore, the main pain nucleus in the thalamus, the VPL (see web page on the thalamus), which handles pain messages going up to the brain is the very nucleus through which muscle fibers traveling down to the body traverse the thalamus. It is a little too much to expect that hypersensitive pain fibers in the thalamus would not interfere with motor signal transmission on its way back down to the body, especially since the same chemical which excites sensory fibers also excites muscle fibers. (All clinicians who do NOT believe their CP patients can suffer severe muscle pains please now hide their faces in shame.)

In some way, this proximity of fibers in the thalamus almost surely contributes to the muscle pain of Central Pain. Yet, again, nothing is known of the mechanisms. Our evidence here rests mostly on the fact that CP patients with VPL injury often have very severe muscle cramps, pulling, tightening, or ache. Whenever any sensory area of the brain is considered, the anatomist MUST ask which motor fibers are feeding their way back down through that very area and ask what excitatory impact the muscle fibers encounter in an area which is chemically messed up by all the acid producing products saturating those zones.

The former assumption that brain pathways are discrete avoided that problem and allowed us to ignore it, but if nerve fibers which use the very same exciters and inhibitors (muscle fibers also use glutamate for excitation and GABA or glycine for inhibition) It is difficult to believe that malfunctions in intertwined sensory fibers of those very same chemicals will leave the motor fibers untouched. Yet, that has been the idea until fairly recently. (Okay, its hard to stay caught up, we were only kidding about hiding your faces)

Believers in this splitting of sensory CP from muscle CP have been called “reductionists” or less kindly, "simple minded" and their days are very likely numbered as the concept of pathway integration continues its exploding number of apparent examples in the brain. Perhaps the most noteworthy example of this is discovery that electrode stimulation of the MOTOR cortex , either M-I (the primary motor cortex or Brodman area 4 which actually dips down into the sulcus or groove which separates it from the sensory cortex), the secondary or supplemental motor cortex (medial Brodman area 6, or the premotor cortex) or lateral Brodman area 6, which receives positional messages from the VPL) are all being explored as ways of suppressing Central Pain. Said simpler, stimulating the motor brain, sometimes helps stop sensory pain.

This is absolute heresy compared to what until recently was the “traditional” idea of strict separation of pathways, an idea which is rapidly becoming the minority viewpoint.. However, motor cortex stimulation apparently works in some people to help Central Pain, although it has not been well worked out and includes risks, including very undesirable reactions, such as the creation of a phantom limb, have been reported. The cramping in a particular person may be either in the proximal muscles, carried by vestibulospinal and reticulospinal tracts, or the tightening may be in the more distal muscles, carried by the corticospinal and rubrospinal tracts.

Strangely, the power of the motor signal appears to be stronger the further out one goes in the nerves, with the nerve potentials in the latter two tracts (CoS and RuS) having notably increased strength of firing over the former two (VeS and ReS). This is weirdly reminiscent of the centripetal predominance of pain from touch in central pain, where distal structures clearly predominate where severity of touch pain is concerned. This fact has been well known since the time of Dejerine and Roussy.

Taken this way, the many bizarre symptoms of Central Pain become not only acceptable but positively likely, as we learn how pathways that were formerly thought to be isolated bunches turn out to be promiscuously familiar with everyone in the neighborhood.

As stated, each thalamus is about 2x2x3 centimeters and sits right in the center of the brain. It is part of the diencephalon which is the lower part of the forebrain. It is the main sensory relay of the brain, receiving sensory messages, filtering them, and relaying output to the cortex.

That’s it for now!. That’s all we know! The rest will have to be speculation since the scientists keep changing their minds. In fact, we are almost surely wrong about what we have already said, since there is very strong evidence that the thalamus is, shock the world, a relay for some motor tracts below it and above it, as well as a sensory control center.

After all these years, the thalamus could not be more controversial because its behavior simply will not conform to conventional brain theory. At one point, neuroscientists confidently declared that each neuron could have one “and only one” neurotransmitter”. That was tidy, but unfortunately, very false.

In the fallout, at least anatomists had the comfort of saying the front of the cord is for motor function, the back is for sensory function. The same was said of pathways and structures. They were either motor or sensory. This made for logical arrangements that suited the organizational mind of the anatomist, but it was not fully true.

It is not possible to name pathways and structures which are fluid, changing function freely under different chemical influences and so the papers were published, one after the other, describing how cells “looked” under the microscope, which direction the fibers faced, etc. The subdivision of all this was called cytoarchitecture, and it was nearly all done in rats. To this day, we know twice as many nuclei in the rat brain as we do in the human brain, which weighs six hundred times more.

With the demise of the “one neuron, one neurotransmitter” dogma, cytoarchitecture began to be somewhat passé and the young Turks of the field moved into chemoarchitecture, with a picture of the brain as consisting of areas or zones where the population was variable, but one could attempt to overlay these discrete chemical pathways onto the old schema of brain structures based on subtle, sometimes imagined differences in the appearance and orientation of the cells. Just when we thought it was safe to leave the water of cytoarchitecture, however, the new tensor analysis MRI revealed that fiber orientation is valuable for determining which cells close to each other actually belong together, so fiber orientation has been given new life.

Existing theory cannot circumscribe the notion of a fluid brain, with fluid structures where boundaries were simply means of isolating chemical pathways. It was simpler when Serotonin was supposed to be a neurotransmitter for muscle, Substance P for pain, etc. with structural names concocted to reflect the chemical content. There was, nevertheless, the familiar anatomical attempt to make structures locatable, identifiable, and categorical. This approach will not hold, but anatomists have had a hard time not trying to make the brain divide as neatly as the body. Neurons simply have an open mind. They make new friends and they value diversity. One may produce mostly one type of ion channel while the nearest neighbor has a different composition.
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"WELCOME TO THE DESERT OF THE REAL" (or, this stuff is tough to grasp)

The thalami are divided by a linear grouping of cells in a dividing “wall” called the lamina. Long before Pat Wall and his associates were to show that there was not one spinothalamic pain path winding through the cord, but seven, this lamina was used to name thalamic structures. One could start by saying a nucleus was either inside or outside the dividing wall of the lamina. If one added forward and backward (ventral and dorsal) directions and also top and bottom (rostral and caudal) then one could get back to the familiar task of naming parts of the thalamus. You can find them in any neuroanatomy text, but unless you look at the biochemical level, you will look at them largely as a tourist.

Chemoarchitecture refuses to cooperate with strict cytoarchitecture, with fibers subserved by different chemicals refusing to package neatly in one area. Once again, symptom architecture was needed. (Symptom architecture is where you come in when you complete the survey on this site.) It is easier to speak of a perceived sensation and watch parts of the brain light up on functional MRI than it is to provide a detailed chemical menu for that sensation.

It was observed that stimulation of one part of the thalamus blocked speech, and the entire dorsal region of the thalamus, the pulvinar, was associated with the visual system, the remaining parts were assigned various sensory functions and the thalamus was named the “main sensory relay”.

The brain also was divided into main motor and sensory areas, the precentral gyrus and the postcentral gyrus, respectively. Other parts of the brain which functioned were looked at as assistants to the main areas. Fairly early, there were signs of trouble for the "it's all so simple" society of the brain. In the lamina there were prominent nuclei. One, the centromedian (CM) actually starts at the bottom of the medullary lamina of the thalamus but extends about 8 millimeters up.

To its outside was the ventrocaudal nucleus (Vc) and to the inside was the parafascicular nucleus. Altogether they were called the CM-Pf complex. The CM itself was said to consist of two parts, a large celled central magnocellularis part in back and a small celled central parvocellularis part in front and below. The small celled part is huge in humans so Mehler, a great neuroanatomist, decided that it was the true CM in humans. An extension of the wall-like lamina splits off a dorsal portion, the middle third of which is called the central lateral nucleus. Other just preferred to speak of the intramedullary lamina, sometimes abbreviated as the iml nucleus.

Bowsher, Mehler, and Dekaban argued over the precise margins of the CM and CL and a semantic argument arose over where the terminations of the spinothalamic (pain tract) fibers terminated. In 1960 Mehler theorized that localized pain (epicritic) referred to the ventroposterolateral nucleus (the VPL ironically being at the anterior part of the Vc, with the VPM being posterior) while poorly localized burning referred to the CL. However, Mehler doubted his own theory because there were large numbers of fibers going to CL from the cerebellum, which until recently was thought of as a strictly motor structure, and the CL was part of the “sensory” center. Mehler eventually caved in entirely when he found reciprocal relays between CL the medial globus pallidus, and from area 4 (the nonprimary motor area of the brain).

Mehler had been more right than he knew since the cerebellum has pain inhibition functions not known until very recently. Nevertheless, he apparently could not abide the untidiness and abandoned his early theory. Since then, more motor connections to the CL have been found from the substantia nigra, vestibular nuclei and “motor” zones of the reticular formation. Today, anatomists favor the idea that epicritic pain (pain easily placed in a body location) goes to the VPL nucleus and protopathic pain (poorly localized pain) goes to the intralaminar nuclei. The emotional aspects of pain are said to travel up to the submedius just below the CM and then up to the cingulum. What is important here is that very important integration of motor and sensory functions is occurring in a structure formerly thought to be exclusively sensory. Removal of brain parts (ablation) to relieve pain was based on the old anatomical ideas, and some feel favorable the favorable surgical reports on ablation persisted long after the old anatomical ideas had been discarded. Not all approaches stayed mainstream. There were even ablations in the pulvinar which were said to relieve pain, based on theory which is incomprehensible, but these results have not been reproducible.

Theory has it that the spinothalamic (pain tract coming up from the spine) relays to the Vc, Vim, and CL nuclei of the thalamus. Lesions in any of these areas are sometimes present in post-stroke Central Pain. The Ventrocaudal (sometimes termed ventrobasal) is traditionally felt to be highly related to tactile pain and to receive lemniscal fibers (touch fibers from back of cord felt to carry the lightning pains of CP) as well as spinothalamic fibers (fibers in the side and front of cord—thought to be responsible for the dysesthetic burning in CP if they are damaged).

The CL, or intralaminar nucleus is discussed above. The Ventrointermedius, which receives fibers from the Spinothalamic and Cerebellar tracts, catches our attention because it is typically included with the CL when ablative thalamotomy is performed for Central Pain. Stimulation of the Vim has been observed to cause slight tremor. It is very hard to separate the consequences of Central Pain itself from other aspects of the injuries which cause it, such as mild spasticity, but we have received occasional reports of slight tremor in Central Pain, EVEN IN QUADRIPARETICS with cord injury. The real incidence is unknown since many neurologists do not perform tests aimed at differentiating CP from spasticity, if there is a true distinction. A real distinction is likely since the cortex and injury to upper motor neurons certainly can cause spasticity, but the minor variety seen in CP seems different clinically.

Likewise, passive movement of a joint in certain Central Pain patients can be followed by a withdrawal reflex, moving the joint away from the point of contact. This is not known to occur, unless the CP patient is unaware that they are about to be touched, suggesting the possibility of some cortical inhibition of this when awareness is present. This has a similarity to unmasking of the spinal protective reflexes as Haerer has pointed out, so it is unknown whether it is truly part of CP or is part of some larger injury to the cord. Sudden auditory stimulus or movement of a someone toward the CP patient has also been observed to increase the “spasticity” element in some. The problem is that these signs are very subtle and it is unlikely the doctor would be aware of it, and highly likely the patient would link it with motor phenomena of the Central Nervous Injury injury which is separate from the Central Pain.

It is hard to know if Vim is in any way involved with slight tremor seen occasionally in CP. When present, it is often accompanied by inability to keep steady pressure or position of the hands and feet. For example, if one so affected were watering the yard and keeping the thumb in the stream to spread the water, the thumb would quiver. If in the sitting position, the foot is put in tip-toe position, there soon comes a rhythmic tremor of the foot and toes. Vim is impressive because there is a high level of background electrical activity which is readily picked up by an electrode inserted into the area. Even more interesting is that when a joint or muscle is passively or actively moved, the spiking electrical discharge in Vim is highly stimulated, whereas touching the skin does not do this. The neurons responsible for this are called kinesthetic neurons, which probably constitute about one fifth of the lateral Vim. Because proprioceptive muscle spindle Ia fibers go to Vim, it is tempting to feel it may be part of the very common atopoesthesia (diminished sense of body topology, or loss of the “brain map”, which can be restored at points of touch which cause pain.

Dejerine and Roussy, the fathers of Central Pain research, felt that atopoesthesia was a very important part of the diagnosis. Neurologists today are more prone merely to write this off as loss of proprioception (joint position) but there is strong evidence that more is involved, since loss of the “body map” is a broader phenomenon than loss of sense of joint position. Most CP patients retain sense of joint position even if they have atopoesthesia with regard to their distal extremities. These ideas have probably been incorrectly confused and a return to Dejerine’s analysis of atopoesthesia would a positive step. It is peculiar that painful touch restores the sense of the dimension of the body part in that particular area of pain.

Sensory nerve tracts which have an arrangement matching the body arrangement are said to be somatotopically arranged. The somatotopic arrangement of normal pain fibers in the thalamus stimulates the curiosity that thalamic dysfunction The body shape is distorted in central pain, with the distal parts, which also have the most distinct and precise touch, feeling larger in relation to parts with less pain. This undoubtedly contains hidden clues about pain processing in the brain, but no one has, as yet, deciphered those clues. The primary sensory area of the brain, SSI, is also, of course, somatotopically arranged.

Beric reported kinesthetic dysesthesia (pain with movement) in Central Pain in 1996, including one CP patient who was paralyzed from the pain of movement despite an intact motor unit.. Our own database contains many reports of severe, disabling, muscle pains. The symptoms nearly always involve sensations consistent with the sensory arm of the gamma motor unit, or the muscle spindle. There were descriptions of “confinement cramps” which seemed to be a perception of hypertonus in the muscle, such as dysfunction in the spindle might generate.

We have looked in the literature for some locus in the thalamus where abnormal function might upset spindle function and result in symptoms which seem to be almost certainly related to the spindle sensors of muscle tone, ie, the sensations of increased tone, tightness, drawing, the now famous, “MS Hug”, and cramps. The Vim may be the very nucleus mediating this since Hassler placed afferents from the muscle spindle Ia fibers in the external part of Vim.

The contributing lower path of these fibers is probably the spinocerebellar tracts leading to cerebellothalamic tracts and finally to Vim. Vim neurons show degeneration after cortical ablation, but the changes were linked to ablation in the anterior parietal or frontal cortex, NOT the postcentral gyrus (the traditional sensory area). Of course, spindle pain refers to the central sulcus, not the gyrus, so the data on the gyrus does not really establish whether somatosensory ablation should be expected to attack spindle pain..

We must comment on the articles you will read about brain ablation. That means injuring or lesioning of the thalamus for relief of central pain. We could have more enthusiasm for this topic if our database did not contain people whose central pain was CAUSED by lesioning of the thalamus, during attempted ablation surgery for relief of other types of pain. We also have some who received NO relief from thalamic ablations and others whose relief was short lived.

Yes, we know those advocating thalamic lesions are brilliant and have lots of data. We just aren’t getting the kind of confirmation that makes us comfortable with this whole area. We do, however, thank the stereotactic surgeons who have been removing thalamic parts for contributing to our knowledge of thalamic anatomy. As early as 1976, Van Buren reported central pain from lesioning in the Vc and Ohye cautions against any lesioning in Vc. Most lesions of late have been created in the intralaminar nuclei, where this procedure is still performed. It is controversial. It is worth mentioning that there are reports of lesions in the PVN nucleus of the hypothalamus abolishing pain from noxious heat. We do not know whether this relates in any way to the “burning” of dysesthetic Central Pain.

Next, we address thalamic stimulation. When certain surgeons lost faith in removing parts of the thalamus, they decided to stimulate those same parts. The idea is to cause a paresthesia or buzzing sensation to help lessen the pain. This is sort of like TENS units. Without accomplishing all that was wanted by stimulating “sensory” areas, some went on to stimulate MOTOR areas. A fair number of centers have gone one better than this and are stimulating the MOTOR cortex in the brain, let alone the thalamus, in order to find relief for Central Pain. Canavero has reported creation of a phantom limb through stimulation of the motor cortex, yet generally favorable reports are being published. We suggest a clear commitment by any neurosurgeon treating spinal cord injury with vascular clips to use tantalum or other nonmagnetic materials since access to MRI is vital. If motor cortex stimulation becomes common, this protective step will become even more important.

Sergio Canavero is a highly respected researcher on Central Pain in Italy and helped write the Harvard Press monologue on the topic by Pagni. We hope this gets sorted out.

Carl Saab bowled over the pain world by finding pain suppression in the cerebellum, which was thought to be as motor as motor structures get. He had collaborated on prior work which showed dense fMRI signal in the vermis (central midline part of the cerebellum) and he later found definite action in the nucleus fastigius to suppress pain signal. The vermis does have connections to the thalamus. Most have not even read Saab’s work yet, let alone have an explanation for it. He has made one of the great breakthroughs in pain medicine and no doubt will continue to make valuable contributions. He left our mouths hanging open and we hope he will hurry and thread it all out so we can say, “Oh yeah, I knew that, I knew that”. In the meantime we have no clue.

Our comment on this is that anatomists are having a very hard time making their theories more than temporary. Therefore, we insist that doctors stop questioning our pain on the basis of transitory conclusions anatomy. They have no right to question our muscle pain, which can be very severe. We think it should be the other way around. The anatomists should attempt to correct their theories to be consistent with what is experienced in central pain. There is no motive for patients to misrepresent. It is simply that there is no vocabulary by which to describe some of the symptoms of Central Pain. We hope to see continued advancement in cytoarchitecture and chemoarchitecture, but we also want their theories to explain the symptom architecture of Central Pain. We doubt they can do this without considering the periaqueductal gray, the vermis, and the reticular system in the medulla.

Tarek Samad has blessed the pain world by discovering that when central pain occurs, the same nerve acidosis which characterizes nerve endings in the skin occurs in the thalamus. There is some evidence that people vary in the way signals traverse the thalamus and that perhaps the final common denominator of Central Pain is nerve acidosis caused by prostaglandin E, interleukin-1-b, and the other ingredients which so effectively create an acid soup beneath the skin when a nerve is injured. This outpouring of venom in the thalamus appears to result from stimulation of the genes in the cord and areas above to produce exciter proteins and kinases to activate them. Pain itself may be nothing more than acid on nerves. Central Pain may be nothing more than LOTS of acid on nerves. It is true that the burning pain coexists with loss of sensation (Boivie’s paradox) but this may be due to injury to two different types of nerve fibers and not exactly identical processes.

We do not know if stopping the pain will give us our sensation back, nor if it will restore our sense of body topography, but we will take the pain relief and worry about the other symptoms in turn.

The thalamus is not uncharted water, it simply that the charts need updating and the “unknown regions” need to become known. What the explorers thought they were seeing was indistinct and the old anatomy needs to be redone with the new investigative techniques. We need to stop referring to the thalamus as the sensory relay center and begin referring to it as a structure which integrates both sensory and motor information. This should halt the brutal and stupid attacks on innocent patients by doctors who are in denial about muscle pains and abnormalities as an important part of Central Pain. Dysfunction in the thalamus almost certainly leads to muscle as well as touch and temperature pain. We hope more research money is provided soon, as Central Pain will not wait. It bores on through the soul, destroying self and identity. The thalamus is the mother lode of pain. We appreciate the scientists who have been panning for gold in the lower tracts and pain structures, but now it is time to study the control center.

Dr. Carl Saab has pointed out that we cannot really attribute higher faculties to nerve tracts, as we do not know how they interrelate. We must look at how the connections are elaborated and what other signals converge on any tract before we can draw conclusions. This means that the traditional notion of assigning A SPECIFIC function to A SPECIFIC tract or brain region is probably incorrect. This will be a hard habit for the anatomist to break, but it must be done. We must appreciate there is architecture going on at other levels.