Monday, July 22, 2013

Melzack & Katz, Pain. Part 17b: Stress and adrenals

The paper, Pain.

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

Part 17: The stress of it all


So far in this subsection, Pain and Stress (scroll down), we have caught glimpses of what stress does to the brain's control of body systems when injury threatens homeostasis (see yesterday's post). Basically, the "critter brain" (internal regulation system)
  • sees the threat
  • reacts instantly
  • keeps body systems functioning or else stops them temporarily (..if stopping them doesn't constitute a threat to its own existence, e.g., digestion)
... all by itself, no help required from the big fluffy human brain out front and to the sides, thank you very much. I can't help but be reminded of Scotty in the engine room. 


Today we continue pondering Melzack and Katz's paper - nice and slow, because it is still so delicious. They still are far from talking about the conscious aspects of brain, those more rostral, the perceiving, meaning-making parts of it. This is still the autonomic/automatic critter brain:

"At the same time, the perception of injury activates the hypothalamic–pituitary–adrenal (HPA) system and the release of cortisol from the adrenal cortex, which inevitably plays a powerful role in determining chronic pain. Cortisol also acts on the immune system and the endogeneous opioid system. Although these opioids are released within minutes, their initial function may be simply to inhibit or modulate the release of cortisol. Experiments with animals suggest that their analgesic effects may not appear until as long as 30 min after injury."
This is interesting, something I had never considered before:  Think of it - our brain may have evolved the ability to cause the squirt of caustic cortisol everywhere as a result of becoming perturbed by stress, but also evolved an immediate soothing balm so that the body won't react to being chemically ripped up quite so much! This deserves a closer look, but first, let's review the alarm system itself:

1. Brain perceives a threat, takes action via HPA axis:

HPA axis
HPA: The pituitary squirts out ACTH, which tells the adrenal cortex to make and release/unleash corticosteroids, e.g., cortisol, which, when they enter the bloodstream, circulate everywhere including the brain, including the pituitary, and inhibit further production of ACTH.

2. Sympathetic nervous system alerts the adrenal medulla:

The sympathetic NS reminds me of old-fashioned message tubes that used to be used in hospitals and other large enterprises, like factories, where a physical piece of paper was sucked into a vacuum and sent as if by magic instantly to a recipient at a given physical location. But I digress.

Adrenals: two glands in one

We need to consider for a moment that the adrenal medulla is not the same thing as the adrenal cortex.

Let's take a moment to don some scuba gear, dive off the side of this lovely boat we are sailing down this beautiful river in.. take a look at what's down in the water by traveling into it for a little while. Maybe we can make better sense out of how all this works together, if can we find some clues.

Let's look a bit closer at the adrenal gland, where cortisol is produced: this surgical wiki explains the situation.

"The adrenal glands lie superomedial to the upper poles of both kidneys. Each adrenal gland comprises a medulla and a cortex, and each component has a distinct embryological origin. The adrenal cortex is of mesodermal origin, whereas the adrenal medulla arises from neural crest cells along with the sympathetic ganglia. The adrenal medulla produces catecholamines, including adrenaline, noradrenaline and dopamine and is under the control of the sympathetic nervous system. The adrenal cortex produces glucocorticoids (cortisol, corticosterone), mineralocorticoids (aldosterone) and sex steroids (oestrogen, testosterone, dihydroepiandrosterone). The adrenal cortex is under the control of adrenocorticotropic hormone (ACTH), a hormone produced by the pituitary gland."

Aha!! Neural crest versus mesoderm, yet again. Of course tumour surgeons are going to know about this, because different tissue origins will give rise to distinct kinds of tumour growth and behaviour - makes sense.

The adrenal medulla is ectodermally derived. It's still neural. Same as Schwann cells, and peripheral neurons, satellite cells. These cells are basically neurons, just not long and thin - instead they are short and blobby same as regular body cells, but even though adrenal medulla looks like just regular gland-blobby tissue stuff, it’s neural - probably has clearer reception and faster reaction time and signalling speed than other kinds of tissue.

Nice set-up - brain signals the adrenal medulla, because that's just so much faster.
The medulla makes all the same sort of signalling molecules the brain nuclei do - “..including adrenaline, noradrenaline and dopamine” so it’s like a little brain proxy.

Adrenal medulla squirts motivation juice on the adrenal cortex, which signals, “ChopChop squirt that sugar-manipulating juice you make, NOW! We need to get this whole rig, this whole big meat body, out of harm's way IMMEDIATELY or it will be just meat.”

The adrenal cortex comes from different embryonic tissue origin. It makes different stuff, more hormonal, steroid type stuff.
Bam, as soon as it gets the signal - in stereo, because it can smell adrenocorticotropic hormone from the pituitary gland in the hypothalamus arriving in the bloodstream too - it does its thing. Squirt!


The two faces of cortisol
Here is what cortisol is about:

"Cortisol is an essential hormone for survival because it is responsible for producing and maintaining high levels of glucose for rapid response after injury or major threat.

Very interesting... sort of like a total body trophic factor, and yet.. it's classified as a non-tropic hormone

Here is the Wikipedia page on cortisol. Looks like it interacts with insulin and just about everything else besides. It counters the immune system for varying lengths of time.


"However, cortisol is potentially a highly destructive substance because, to ensure a high level of glucose, it breaks down the protein in muscle and inhibits the ongoing replacement of calcium in bone. Sustained cortisol release, therefore, can produce myopathy, weakness, fatigue, and decalcification of bone. It can also accelerate neural degeneration of the hippocampus during aging. Furthermore, it suppresses the immune system."

Yikes. It's like the alarm system in your house weakens the foundation and wall support beams themselves, and can create wear and tear of the control panel itself, if one isn't careful. 

So, here is our physico-existential dilemma: "an essential hormone for survival" is also "a highly destructive substance" at exactly the same time. Sounds like life is a death trap. Which it is. And we all have to just get used to the bare fact of it. 

How do we get around that? We can't. Stress (if nothing else gets to us first) will eventually kill us all. All we can do is avoid cortisol's ups and downs as best we can, and learn to live with whatever amount we need/can't avoid.. 


More to come. 


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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