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With special thanks to Nobel Laureate, Dr. Francis Crick, for his contribution to this article on the insular cortex, and to suggestions by Dr. Carl Saab at Yale for information on the sodium channels.

This is another research article addressed primarily to those who send in highly sophisticated questions to painonline, or who seek enablement to read the medical literature. If you are a professional, you will handle this easily, but if a layperson, this article should be read in two or three sittings.

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