Johns Hopkins Pain Scientists Moving Ahead

A technical article, but still encouraging. We love it. We absolutely love it. We have already reviewed Frederic A. Lenz’s ideas on misallocation and central pain. Now he and his progeny at Hopkins are blasting the lid off old studies of the thalamus.


For many years, it has pretty much been accepted as axiomatic that pain has to be “non-Cartesian” which is to say that it is a complex mixture of things, and we need not think we can identify discrete pain in the brain, since it is in a lot of places, yet is nowhere in specific. If you wanted to get really erudite about it, a person declaiming the issue might say, “You cannot separate the medial thalamus from the lateral thalamus”. This was still the same idea, you cannot separate the emotional thalamic routes from the strictly sensory ones. Some have thought pain has only a chemistry and no place at all. Now it would appear that a slight crack exists in the whole notion.

That crack has not shown itself where we expected, in the Ventral Posterior Lateral (body) and Ventral Posterior Medial (face) nuclei, the place where Pat Wall found multiple ST tracts gathering to pour input into the thalamus. Rather it has been discovered in the ventral caudal nucleus, the primary somatic sensory nucleus of the thalamus.

No one better to discover it than Lenz, who has already shown a flair for wondering where the lost touch sensation of light touch in central pain is picked up elsewhere in the brain. (shifting receiving areas being part of brain plasticity) Just a word of explanation. Scientists use the word “plasticity” to mean several different things. In general, it refers to a kind of redundancy in the brain, which makes it able to be malleable in function when the need arises. It means that generally the brain can move a function to another area if it absolutely has to. A good example of this would be allocation of brain “thumb” receptory centers to the nearest finger, if the thumb happens to be amputated. Specifically, pain scientists use the word to mean that genes in any given cell, the glia in particular, are capable of having their genes altered by pain, and to in turn alter the genes in neurons. There are about five glia for every one neuron. The genetic alteration guarantees an imbalance with pain exciters becoming “toxic” and actually blocking pain inhibitory chemicals. Another use of “plasticity” is as a catchall to fudge on whatever characteristic of brain function is unexplainable–the scientist can still sound scientific if he write things off to “plasticity”.

Lenz’s idea is that in cord injury, touch was handed over to the nearby pain from light touch neurons. This is still valid theory and bespeaks Lenz’s attention to location. It also attests to the brain’s dislike of being shut off from the exterior environment. Moving exteroception to interoceptive mechanisms doesn’t really work. We wind up with central pain, which is a torture to say the least. However, interoception relies more on the autonomic nervous system, which can bypass cord, and possibly the vagus nerve, (cranial nerve X) which is part of the conscious nervous system participates in the cord bypass as well.

In theory, we are all for bypassing injured cord, but sensory bypass seems to wind up at a pain place, inlcuding the pain components of the MOTOR cortex, just across the central sulcus from where it should nomrally wind up, in the somatosensory cortex. Thanks, but no thanks. Central Pain is beyond description. It is “pain beyond pain”. The external environment has become too painful. When even light touch is agony, we need some relief, and quickly, PLEASE.

Chemists have done so much. The studies of anion reversal, (use SEARCH for Jeffrey Coull at this site) whereby behavior of calcium at the cell membrane prevents any kind of pain impulse leaving the neuron except the excitatory ones (and results in reversal of inhibitory impulses into excitatory impulses–how fair is that?) has revealed a great deal about why Central Pain subjects suffer so.

The stunning discoveries of chemoarhitecture have almost overwhelmed the anatomists, who have struggled to grasp all that the biochemists have learned about hypersensitization in nerve injury. Many of the pain chemicals, the nerve growth factors let loose, the acidifiers, the kinases, and the fatty acids which wreak havoc in nerves, have proved to be ubiquitous in the injured nervous system, making location studies difficult.

And so we are happy to see Lenz and associates make this breakthrough finding on the Vc. We are after the evil little so and so neurons and want to kill them like the cockroaches they are in our injured nervous systems.

Brain and pain neuroanatomy is a rarer skill than you might think. Some think only Bogduk in New Zealand can call himself a pain neuroanatomist, but the recent work by Bud Craig shows there are others. Since the founder of the painonline database (Wall/McHenry CP database), Dr. Patrick Wall, died, we have hoped for someone to pick up the gauntlet and run with it. We are so happy to see it happening.

Pain coming in to the Vc appears to follow roughly a topographic arrangement which means the anterior Vc nucleus is more or less upper body and the posterior is more or less the lower body.

A great deal of interest has recently been directed at Hopkins at the interoceptive system of the brain, the parts which inform the brain of the state of affairs WITHIN the body. Pain is presumably part of this system.

Recently, one of Ron Tasker’s associates at Western Toronto, now moved to Johns Hopkins (Hopkins usually either has the best or it goes and gets the best if it can), has continued to try to think more about the specifics of how pain is specifically located, ie is “non-Cartesian”. The surprising finding is that pain IS a little bit Cartesian. (Descartes was the one who used the X,Y,Z axis to describe space, so things with “bright lines” and able to be spatially defined, are sometimes said to be Cartesian)

What we mean by this is that studies on the ventral caudal nucleus of the thalamus, the primary sensory nucleus of the thalamus, have revealed TWO methods of input. This stimulation produces two different types of EXTEROCEPTIVE responses. Bagley, Lenz and others found when considering how the spinothalamic tract (STT) gathers to have its information received at the Vc nucleus of the thalamus, one area of the ventral caudal (Vc) when stimulated, createa a sensation of pain, which is ON/OFF or in computer speak, BINARY.

When the second area of the Vc is stimulated, a graded or ANALOG signal is produced. So pain traversing the thalamus is non-Cartesian, but also kind of Cartesian See Neuroscientist. 2006 Feb;12(1):29-42 “Psychophysics of CNS pain-related activity: binary and analog channels and memory encoding”. Bagley CA, Ohara S, Lawson HC, Lenz FA.

The scientists themselves, perhaps hoping not to offend anyone and far too accomodating to the “pain is non-Cartesian” mantra heard repeatedly at every pain meeting, said it this way:

“It has recently been proposed that the STT contains a series of analog-labeled lines, each signaling a different aspect of the internal state of the body (interoception), for example, visceral/cold/itch sensations. In this view, pain is the unpleasant emotion produced by disequilibrium of the internal state.”

Further:

“…stimulation of an STT receiving zone (thalamic…somatic sensory nucleus, ventral caudal) in awake humans produces two different exteroceptive responses. The first is a binary response signaling the presence of painful stimuli. The second is an analog response in which nonpainful and painful sensations are graded with intensity of the stimulus.”

After some pretty sophisticated human studies, the researchers concluded:

“Such stimulation can evoke both the sensory and emotional components of previously experienced pain. These results illustrate the diverse functions of human pain signaling pathways.”

It may not sound revolutionary, but it is. The entry area of the spinothalamic tract splits into TWO mechanisms which have pathways. This is close enough to Cartesian to be revolutionary. Although the authors do not risk a scientific uproar by saying this, we will say it for them. We do so because we do not like physicians who claim pain is all psychological, and prefer this new scheme where a major connection to the limbic and motor systems is shown, but also a graded analog registry is highly suggested. Central Pain patients are well aware of BOTH of these phenomena. When there is stress, we are aware of emotional dread that sets in, but the spontaneous burning is there and capable of evocation with or without external or internal emotional input.

This research follows an article of almost equally stunning revelation from Lenz, Lee and others, revealing just how important the ventral caudal nucleus is. See “Pain and temperature encoding in the human thalamic somatic sensory nucleus (Ventral caudal): inhibition-related bursting evoked by somatic stimuli. J Neurophysiol. 2005 Sep;94(3):1676-87

Those of us weaned on the VPM and VPL nuclei of the thalamus as the heart of pain are not entirely left in the dust, however, as recent research by Bud Craig at Barrows Institute has shown that Lamina I (see role in hypersensitization by using SEARCH at this site) activity is linked to BOTH the ventral caudal AND the VPM and VPL. See Craig AD. J Comp Neurol. 2004 Sep 13;477(2):119-48. “Distribution of trigeminothalamic and spinothalamic lamina I terminations in the macaque monkey.” Dr. Craig states regarding terminations of the spinothalamic tract:

“Terminations consistently occurred in two main locations: a distinguishable portion of posterolateral thalamus identified cytoarchitectonically as the posterior part of the ventral medial nucleus (VMpo) and a portion of posteromedial thalamus designated as the ventral caudal part of the medial dorsal nucleus (MDvc). In addition, isolated fibers bearing boutons* of passage were observed in the ventral posterior medial and lateral (VPM and VPL) nuclei, and spinal terminations occurred in the ventral posterior inferior nucleus (VPI)”.

Of interest in view of our recent discussions here of the hypothalamic paraventricular nucleus and pain, it is noteworthy that Dr. Craig also found regarding STT afferent neurons:

“Isolated terminations occasionally occurred in other sites (e.g., suprageniculate, zona incerta, hypothalamic paraventricular n.”

The zona incerta is now felt to carry throughput from the thalamic reticular nucleus (pain awareness).

Thus, pain really gets around, bringing in attention, awareness, and emotion, but pain has a PLACE. When we find that lair, the nexus of CP’s heartbreak and agony, we are going to kill it. Count on it.

We are so grateful for the masterful work of these great scientists. They go largely unsung for few possess sufficient knowledge to know how important their work is. The mysteries of pain are unfolding and we express appreciation to those doing the revealing. We are in pain, and it is hard to be patient.
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Remember, the STT or spinothalamic tracts (anterior and lateral in the cord) carries the dysesthetic burning of Central Pain, while the muscle pains and lightning pains of Central Pain are carried in the posterior cord.

*A bouton is a swelling from which connections radiate. It is rounded, like a boutonnierre worn to a formal dance. For the examiner using a microscope, it is like a traffic direction sign saying things are headed this way.

Criag’s study is particularly unique and valuable in that he did it in primates. Trigeminal pain fibers supplying the face do NOT go directly to the brainstem (TOUCH fibers do) but rather descend into the cervical cord as low as C5 in some people, and meet up with the spinothalamic pain tracts coming upward and carrying pain below the face. The trigeminal nerve, which is cranial nerve V, supplies only to the angle of the lower jaw. The pain portion of the tract is sometimes called the quintothalamic tract (quinto meaning cranial nerve five) Craig traced out both sets of tracts.