Sunday, August 04, 2013

Melzack & Katz, Pain. Part 17j: cortisol, good or bad? Sensitivity to pain traumatization.

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

At last, back to Melzack and Katz after that last meander through Chrousos and Gold 1992
Here is the paragraph that got us off on that last meander. 
"These speculations are supported by strong evidence. Chrousos and Gold70 have documented the effects of dysregulation of the cortisol system: effects on muscle and bone, to which they attribute fibromyalgia, rheumatoid arthritis, and chronic fatigue syndrome. They propose that they are caused by hypocortisolism, which could be due do depletion of cortisol as a result of prolonged stress. Indeed, Sapolsky71attributes myopathy, bone decalcification, fatigue, and accelerated neural degeneration during aging to prolonged exposure to stress."
My bold. So, cortisol is needed... Wikipedia says, cortisol is:
"..a steroid hormone, more specifically a glucocorticoid, produced by the zona fasciculata of the adrenal cortex.[1] It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat, protein and carbohydrate metabolism.[2] It also decreases bone formation. Various synthetic forms of cortisol are used to treat a variety of diseases."
My bold. I can dimly remember from decades ago people with rheumatoid arthritis being given corticosteroids to suppress their immune system, decrease inflammation (nociceptive input from that), and decrease erosion of their tissues..I think there are more treatment options nowadays. (These are not the same as anabolic steroids, which are more tersosterone-esque..)

Steroid injection?

The medical world seems to love corticosteroids - it likes to inject steroidal stuff into areas of pain.. one hopes they hit the mark and that it helps, but really, there isn't great evidence that it helps in any convincing mega-data way. 

Injecting fancier stuff than steroids doesn't help anymore than regular steroids, and placebo injections work just as well as steroid, apparently. For thumb arthritis at least

"A randomized, double-blind clinical trial by researchers at Hospital for Special Surgery has revealed that corticosteroids are more effective than the more expensive treatment, hylan G-F 20 (Synvisc One, Genzyme Biosurgery), in providing pain relief to patients with thumb arthritis. The study also showed that both of these commonly used treatments provided clinically meaningful pain relief, but so did a placebo injection."
My bold.

Here is a blogpost by Doctor Skeptic on treatment of tennis elbow
Bottom line:
"Nearly every operation being performed for subjective complaints (usually pain) today has not been tested against placebo and is performed for the very reason that Garden did his operation on tennis elbow: because the patients seem to get better afterwards (see my previous blog post for a more detailed explanation of the ‘wobbly tripod’ of evidence for surgery). 
I was going to say that this is a case of (the logical fallacy of) post hoc, ergo propter hoc on steroids, except that steroids don’t work either."
My bold.

There isn't good evidence to inject for low back pain.  (full text)
"There is insufficient evidence to support the use of injection therapy in subacute and chronic low back pain. However, it cannot be ruled out that specific subgroups of patients may respond to a specific type of injection therapy."
My bold. 

Back to cortisol as a stress hormone - what's the deal? Hypo?.. or hyPER? Good or bad? 

Melzack reports that Chrousos and Gold attributed "effects on muscle and bone, to which they attribute fibromyalgia, rheumatoid arthritis, and chronic fatigue syndrome" to hypocortisol. I.e., suppression of cortisol (or maybe the organism's stores of it being depleted?) by prolonged stress leads to these conditions. 

In the very next sentence, Melzack and Katz say, 
"Indeed, Sapolsky71attributes myopathy, bone decalcification, fatigue, and accelerated neural degeneration during aging to prolonged exposure to stress."
I don't quite get the relation of cortisol to bone formation, according to this. 
How does cortisol "decrease bone formation," and at the same time, hypocortisolism contribute to "bone decalcification"? That seems a bit confusing.. 

Further down the Wikipedia page, under Other Effects: bone metabolism, we see this:

Cortisol reduces bone formation, favoring long-term development of osteoporosis. It transports potassium out of cells in exchange for an equal number of sodium ions (see above).[28]This can trigger the hyperkalemia of metabolic shock from surgery. Cortisol also reduces calcium absorption in the intestine.[40]
The possibilities are:
1. Maybe I'm just not smart enough to figure it out. (But I try hard anyway.)
2. Maybe it's just the way it's written in the Melzack paper. One's brain is still thinking about hypocortisolism when he brings up Sapolsky, bone decalcification, and stress, but not necessarily stress that is any longer about hypocortisol at all, but in a sentence directly juxtaposed, and presumably supportive. Excessive secretion of cortisol goes with osteoporosis, according to a cursory glance at this list of papers from Google Scholar from 2013, found by entering "cortisol and osteoporosis"
3. Wikipedia mistake (?) (I don't think so..)

Anyway, at the moment I'm going to go back to what I thought in the first place, which was that too much cortisol for too long eats away bone strength. I'm going to go with Wikipedia and all those other papers, and wag my finger a tiny bit at the Melzack and Katz paper for tripping me up a little. 

More to the point of how chronic pain figures into the picture, here is a paper I found by a group in Germany that provides a rundown of hypocortisolism in disorders that typically present with a triad of stress sensitivity, pain and fatigue - they look at how this triad might be protective; 
Eva Fries, Judith Hesse, Juliane Hellhammer, Dirk H. Hellhammer; A new view on hypocortisolismPsychoneuroendocrinology (2005) xx, 1–7 (full text)
My bold. I gotta say, I have not yet read it terribly closely. 

Moving on. 
The final paragraphs in Melzack and Katz' section on stress and pain: 
"Clearly, consideration of the relationship between stress-system effects and chronic pain leads directly to examination of the effects of suppression of the immune system and the development of autoimmune effects. The fact that several autoimmune diseases are also classified as chronic pain syndromes—such as Crohn's disease, multiple sclerosis, rheumatoid arthritis, scleroderma, and lupus—suggests that the study of these syndromes in relation to stress effects and chronic pain could be fruitful.
Yes. Those are painful. 

Immune suppression, which involves prolonging the presence of dead tissue, invading bacteria, and viruses, could produce a greater output of cytokines, with a consequent increase in cortisol and its destructive effects.
OK, we're back to hyPERcortisol.  
It sounds to me that cortisol, like anything else, has a role in the body but like Goldilocks, too much or too little = not good. 

Immune system
Here are a few more of their thoughts on the immune system.
"Furthermore, prolonged immune suppression may diminish gradually and give way to a rebound, excessive immune response."
For some reason, I picture Alfred Hitchcock's movie, The Birds. Here is the final scene. Revenge of the microglia/seagulls? (Recall that long gliopathy paper we explored.) 
"The immune system's attack on its own body's tissues may produce autoimmune diseases that are also chronic pain syndromes. Thorough investigation may provide valuable clues for understanding at least some of the terrible chronic pain syndromes that now perplex us and are beyond our control."
OK, that sounds perfectly logical. Yes, let's help the "selves" embedded into nervous systems at war with immune systems, who must co-exist with terribly painful conditions, whose nervous systems can't seem to adequately staunch the immune response, or extinguish the painful effects of one that has overflowed its normal banks. 
"In some instances, pain itself may serve as a traumatic stressor."
Absolutely! Or there wouldn't be any such thing as human primate social groomers, such as myself, or any need for us at all anymore, as there would be no need for stress-reducing and hence pain-alleviating physical interaction with a caregiver who has some perceived capacity to elicit descending modulation in a vertebrate/mammal/primate/human nervous system.  
"A recent prospective study in large sample of surgical patients suggests that the construct sensitivity to pain traumatization (SPT) may be a broad-based vulnerability factor for chronic postsurgical pain.73 
Reference 73 goes to  
Kleiman VClarke HKatz J. Sensitivity to pain traumatization: a higher-order factor underlying pain-related anxiety, pain catastrophizing and anxiety sensitivity among patients scheduled for major surgery. Pain Res Manage 201116:169177. (free access!!)
This paper has only been out a couple years. I see Katz was involved as a co-author! This may take us down yet another side river. But first, let's get to the end of the section on pain and stress. 

"SPT was derived from a hierarchical factor analysis of items from several pain related anxiety measures and describes the propensity to develop anxiety-related somatic, cognitive, emotional and behavioral responses to pain that resemble features of a traumatic stress reaction."
Hmmnn.. if this is a real thing, I hate to think what my particular score would be. 

"The results showed that the total SPT score before surgery distinguished between patients with and without chronic postsurgical pain at the one-year follow up. That is, preoperative SPT scores were significantly higher in patients who went on to report persistent pain compared with those who were pain-free at the one year follow-up." 
Interesting. It sounds like there might be some ability now, for the health care system, to determine who might require special handling, and sort them from the ordinary folk who endure surgically induced trauma without much problem, before they have surgery. 
"SPT may serve as a predisposing factor that triggers specific expressions of pain, such as pain catastrophizing, pain anxiety, and pain avoidance, each of which may have different and unique impacts on the quality of the pain experience as well as on the maintenance of chronic pain."
I haven't read this SPT paper yet, but I think the idea is great, a proposed way to pick out those who won't do well pain-wise after surgery, before surgery!! Maybe find ways to handle them pre-op, or maybe choose a less invasive form of treatment first, or maybe decide not to operate at all.. especially if it's just "orthopaedic" surgery and not a burst appendix or something else potentially lethal. 
"Consistent with the role of stress outlined above, once pain is established, it becomes a stressor in itself and may be activated even in the absence of peripheral input not unlike the situation described above for phantom limb pain."
That's the final sentence in this section, and the bottom line: Once it's established, chronic pain is felt as an invasive force, not unlike a constant barrage of "The Birds" flying around one's head and biting and gouging at one's flesh.

It has been pointed out that a big chunk of chronic pain in the general population is poorly managed post-surgical chronic pain, which might have been a whole lot easier to prevent than it has been to cure. So ANYthing that can prevent more people from ending up with it could hopefully bring down the proportion of chronic pain out there in the general public. 

So, even without having read your paper yet, way to go, Kleiman VClarke H, and Katz J! 


Next is a short section,  "Multiple determinants of pain."


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

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