Sunday, July 21, 2013

Melzack & Katz, Pain. Part 17: The stress of it all

The paper, Pain.

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


After establishing the argument against blaming the patient for his or her pain, Melzack and Katz examine stress and its relation to pain. 

It's an interesting section - we will likely learn a lot more about what goes on at the top of the second-order nociceptive neurons, up in the brainstem/brainstem nuclei from which all modulation of the biochemical sort descends, be it inhibitory or facilitatory. It will take a few blogposts to get through the entire section, I expect. 

Anyway, we begin: here is the first paragraph in the section Pain and Stress, in Beyond the Gate

"We are so accustomed to considering pain as a purely sensory phenomenon that we have ignored the obvious fact that injury does not merely produce pain; it also disrupts the brain's homeostatic regulation systems, thereby producing ‘stress’ and initiating complex programs to reinstate homeostasis. By recognizing the role of the stress system in pain processes, we discover that the scope of the puzzle of pain is vastly expanded and new pieces of the puzzle provide valuable clues in our quest to understand chronic pain.69"
Reference 69 is Melzack R. Pain and stress: a new perspective. In: Gatchel RJTurk DC, eds. Psychological Factors in Pain. New York: Guilford Press; 199989106. (full text pdf)

This is from 1999 - Melzack was already mapping out things like cytokines in his conception of the neuromatrix model 24 years ago. 

Here is a very old-timey looking picture of his idea, from this 1999 book chapter:

"Hans Selye, who founded the field of stress research, dealt with stress in the biological sense of physical injury, infection, and pathology, but also recognized the importance of psychological stressors. In recent years, the latter sense of the word has come to dominate the field. However, it is important for the purpose of understanding pain to keep in mind that stress involves a biological system that is activated by physical injury, infection, or any threat to biological homeostasis, as well as by psychological threat and insult of the body-self."

I.e., it's not just about one's personal reaction to external stressors. 
It's about all that biochemical stuff (like the stuff I dragged us through in the gliopathy paper. See section 14 and 15.)
Stress, e.g., nervous system response to being stressed, happens at every level of the (physical, cellular) nervous system, not just at a psychological level. 

(Glia don't really care about consequences to a neuromatrix's future, I'm sure..  they probably 'gliafully' take full advantage of the opportunity nociceptive input creates for them to run out to yet another yard sale and acquire yet more rusty junk with which to decorate their homes&yards... remember, at a cellular level, even though human body cells are pretty cooperative with each other, at a cellular biological level, it's all about whose mitochondria can burn up the most oxygen, and produce the most ATP; all those products nociceptors release at both poles when they become overstimulated acts as fertilizer to surrounding DRG and CNS glia cells, be they ectodermal neural crest-derived or pure mesodermal immune-derived. They are known as "trophic factors" after all... so, from a glial point of view, it's probably like winning the lottery or unexpectedly inheriting a bunch of money from an aunt who just died.)

Honey, we won 6-49!!

Anyway, back to M&K:
"The disruption of homeostasis by injury activates programs of neural, hormonal, and behavioral activity aimed at a return to homeostasis. The particular programs that are activated are selected from a genetically determined repertoire of programs and are influenced by the extent and severity of the injury. When injury occurs, sensory information rapidly alerts the brain and begins the complex sequence of events to re-establish homeostasis. Cytokines are released within seconds after injury. These substances, such as gamma-interferon, interleukins 1 and 6, and tumor necrosis factor, enter the bloodstream within 1–4 min and travel to the brain. The cytokines, therefore, are able to activate fibers that send messages to the brain and, concurrently, to breach the blood–brain barrier at specific sites and have an immediate effect on hypothalamic cells."
Yeah.. that breaching of the blood-brain barrier business... Not just the input itself, but the input from all the 'stress response' going on in the spinal cord. 

The paper by Beggs and Salter on TRPV1 neurons comes to mind. See Beggs et al. 2010, Peripheral nerve injury and TRPV1-expressing primary afferent C-fibers cause opening of the blood-brain barrier. Full access. Here are other articles related to the topic

Back to M&K: 
"The cytokines together with evaluative information from the brain rapidly begin a sequence of activities aimed at the release and utilization of glucose for necessary actions, such as removal of debris, the repair of tissues, and (sometimes) fever to destroy bacteria and other foreign substances. Following severe injury, the noradrenergic system is activated: epinephrine is released into the blood stream and the powerful locus coeruleus/norepinephrine system in the brainstem projects information upward throughout the brain and downward through the descending efferent sympathetic nervous system. Thus, the whole sympathetic system is activated to produce readiness of the heart, blood vessels, and other viscera for complex programs to reinstate homeostasis.70,71

The references go to ..


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

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