Monday, August 05, 2013

Melzack & Katz, Pain. Part 18: Multiple determinants of pain

The paper, Pain.

Part 17: The stress of it all Part 17b: Stress and adrenals Part 17c: Women, pain, and stress Part 17d: Stress, aging, and pain Part 17e: Stress and aging, keeping hippocampal dendrites fluffed up Part 17f: Chrousos and Gold and stress Part 17g: Stress conceptualization through the agesPart 17h: Phenomenology and physiology of stress Part 17i: Pathophysiology of stress Part 17j: cortisol, good or bad? Sensitivity to pain traumatization.


Sailing along now, back in Melzack and Katz' paper, Pain
We are in the (very long, very unbroken) section, Beyond the Gate
We have just finished digesting the long section, Pain and Stress, and are about to move into "Multiple Determinants of Pain":

"The neuromatrix theory of pain proposes that the neurosignature for pain experience is determined by the synaptic architecture of the neuromatrix, which is produced by genetic and sensory influences.
There is a great deal packed into this first, seemingly simple, declarative statement. 
Let's never forget that the spinal cord, while very old and primitive (invented by fish at least a half billion years ago) is pure critter brain, but is still CNS, takes over when threatened, because it has the advantage of seniority and location. Looked at another way, it's the old guard, the first line of defense the entire CNS has, when it comes to defending itself from the rest of the "body."

Lest we forget, let us remind ourselves about all that glial activity we read about in the gliopathy paper, going on right inside the spinal cord.

What is a "glomerulus"? 

I looked up a really old paper, Kerr 1975, Neuroanatomical substrates of nociception in the spinal cord. Why? Because I like visuals, and this paper is full of them. 

I first saw an image based on one in Kerr's paper, in a chapter by the same name by Mary P Galea in Pain, a Textbook for Therapists, 2002, precious because it was pioneering, and because Patrick Wall contributed the foreword. [Chapter 2 is the only bit, besides the foreword, only chapter I liked, actually... the book tosses everything, absolutely everything, in. Like looking inside a hoarder's house. Seriously. In that way it's a good glimpse inside the entire conceptually cluttered-up profession, warts and all.]

But I digress, terribly, as usual... 

The image is that of a glomerulus in the dorsal horn, lamina III. 
This is the seed of a nociceptive input. This is "synaptic architecture." 
Note: "7" are glial lamellae (colour added by me)
There is no escape from glia, or their synaptic protein secretions.
They are everywhere in the CNS.

Bear in mind that the term "glomerulus" is not only to do with kidney function:
It is a basic, tiny, heterogeneous cellular structural unit of physiologic function anywhere. Including CNS.

It's kind of like finally zeroing in on the (at least one, if not the main one) headwaters of the river we've been traveling on for months now, as we journey through this whole Melzack and Katz paper
Here is the original picture by Kerr, way way way back in 1975. I added some colour to the glial portion of the synaptic glomerulus, to add emphasis.  [There are many other gorgeous illustrations in this Kerr paper that help one see at a glance synaptic architecture in the spinal cord. I intend to eventually blog about them. Too bad this old old paper got so buried. Thank you to Mary P. Galea for unearthing it, and placing a marker to it, in that otherwise pretty disappointing (IMO) textbook about pain for therapists.]

The take home point I want to make, is that neural glomeruli are everywhere in the CNS. There are probably no two alike; they are built into much larger functionally operative brain-behavioural systems; I expect they are neuroanatomically fundamental. 

Also, re: glia, recall that Seth Grant wrote a pivotal paper in 2008 about the driving forward of brain evolution by synaptic proteins, and the cells that produce them, astrocytes. See Evolutionary expansion and anatomical specialization of synapse proteome complexity (open access!). 

Furthermore, remember that just this year, Nedergaard showed that human astrocytes are truly something unique when she found a way to grow them in mouse brains and watched the mice become a whole lot smarter and remember things better. Check out Uniquely hominid features of adult human astrocytes, full access. 

Back to Melzack and Wall: 
The neurosignature pattern is also modulated by sensory inputs and by cognitive events, such as psychological stress. It may also occur because stressors, physical as well as psychological, act on stress-regulation systems, which may produce lesions of muscle, bone, and nerve tissue, thereby contributing to the neurosignature patterns that give rise to chronic pain. In short, the neuromatrix, as a result of homeostasis-regulation patterns that have failed, may produce neural ‘distress’ patterns that contribute to the total neuromatrix pattern, and may also produce destruction of tissues that give rise to chronic pains. Each contribution to the neuromatrix output pattern may not by itself produce pain, but both outputs together may do so. The stress-regulation system, with its complex, delicately balanced interactions, is an integral part of the multiple contributions that give rise to chronic pain. The neuromatrix theory guides us away from the Cartesian concept of pain as a sensation produced by injury, inflammation, or other tissue pathology and toward the concept of pain as a multidimensional experience produced by multiple influences. These influences range from the existing synaptic architecture of the neuromatrix—which is determined by genetic and sensory factors—to influences from within the body and from other areas in the brain. Genetic influences on synaptic architecture may determine—or predispose toward—the development of chronic pain syndromes. Figure 3 summarizes the factors that contribute to the output pattern from the neuromatrix that produces the sensory, affective, and cognitive dimensions of pain experience and behavior.21"

Figure 3 goes to the image of the neuromatrix model. 
Reference 21 goes to Melzack's paper, Pain and the Neuromatrix in the Brain, full text.

All the rest of the paragraph has been covered in previous blogposts (see below). 

The last section is "Implications of the Neuromatrix Concept." It includes a recap of phantom limb pain, low back pain, fibromyalgia, followed by "Conclusion."

Our river journey is approaching its own conclusion, the river's headwaters, the "end" that is actually the beginning. Of the river itself. Not our journey up it. 


There are a few blogposts left in here yet, though, before we reach our destination. Let's enjoy the remainder of the sail. 

Previous blogposts

Part 1 First two sentences Part 2 Pain is personal Also Pain is Personal addendum., Neurotags! Pain is Personal, Always.

Part 3a Pain is more than sensation: Backdrop Part 3b Pain is not receptor stimulation Part 3c: Pain depends on everything ever experienced by an individual

Part 4: Pain is a multidimensional experience across time

Part 5: Pain and purpose

Part 6a: Descartes and his era; Part 6b: History of pain - what’s in “Ref 4”?; Part 6c: History of pain, Ref 4, cont.. : There is no pain matrix, only a neuromatrix; Part 6d: History of Pain: Final takedown Part 6e: Pattern theories in the history of pain Part 6f: Evaluation of pain theories Part 6g: History of Pain, the cautionary tale. Part 6h: Gate Control Theory.

Part 7: Gate control theory has stood the test of time: Patrick David Wall;  Part 7bGate control: "The theory was a leap of faith but it was right!"

Part 8: Beyond the gate: Self as mayor Part 8b: 3-ring circus of self Part 8c: Getting objective about subjectivity

Part 9: Phantom pain - in the brain! Part 9b: Dawn of the Neuromatrix model Part 9cNeuromatrix: MORE than just spinal projection areas in thalamus and cortex Part 9d: More about phantom body pain in paraplegics

Part 10: "We don't need a body to feel a body." Part 10b: Conclusion1: The brain generates its own experience of being in a body Part 10c:Conclusion 2: Your brain, not your body, tells you what you're feeling Part 10dConclusion 3: The brain's sense of "Self" can INclude missing parts, or EXclude actual parts, of the biological body Part 10eThe neural network that both comprises and moves "Self" is (only)modified by sensory experience

Part 11We need a new conceptual brain model! Part 11b: Intro to a new conceptual nervous system Part 11c: Older brain models just don't cut it Part 11d: The NEW brain model!

Part 12: Action! 12b: Examining the motor system, first pass. 12c: Motor output and nervous systems - where they EACH came from Part 12d... deeper and deeper into basal ganglia Part 12e: Still awfully deep in basal ganglia Part 12f: Surfacing out of basal ganglia Part 12gThe Action-Neuromatrix 

Part 13: Pain and Neuroplasticity Part 13b: Managing neuroplasticity

Part 14: Side trip out to the periphery! Part 14b: Prevention of pain neurotags is WAY easier than cure Part 14cPW Nathan was an interesting pain researcher  Part 14dBrain glia are from neuroectoderm and PNS glia are from neural crest Part 14e: The stars in our headsPart 14f: Gleeful about glia Part 14g: ERKs and MAPKs and pain Part 14h: glia-fication of nociceptive input 14i: molecular mediators large and small Part 14j: Neurons, calling glia (over, do you read?) Part 14k: Glia calling glia, over. Do you read? Part 14l: satellite cell and neuron cell body interactions, and we're outta here!

Part 15: Prevention of neurobiological hoarding behaviour by dorsal horn and DRG glia is easier than clutter-busting after the fact

Part 16: Apples are to fruit as cows are to animals as nociceptive input is to pain

No comments: