Friday, July 19, 2013

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

The paper, Pain


My my, all that neurobiology, and the wading through thereof, was a gruelling experience.. But at last, we're on our way again. 

Long ago now we put a bookmark in the Melzack and Katz paper. Let's recap what we have covered already. We've looked at the abstract, the introduction, a brief history of pain, gate control theory and how it evolved, and entered the long section titled "beyond the gate" with its many subsections. Of those, we examined phantom limbs and the concept of a neuromatrix, outline of the theory, the body-self neuromatrix, conceptual reasons for a neuromatrix, action patterns, pain and neuroplasticity (which was only a single paragraph), and were about halfway through "denervation hypersensitivity and neuronal hyperactivity" when the fog descended, and it became necessary to wait it out, tackle a bunch of neurobiology in a different quite juicy review paper, which we have just completed. 

Picking up on Melzack and Katz, where we left off: 
"Recent advances in our understanding of the mechanisms that underlie pathological pain have important implications for the treatment of both acute and chronic pain. Since it has been established that intense noxious stimulation produces a sensitization of CNS neurons, it is possible to direct treatments not only at the site of peripheral tissue damage, but also at the site of central changes (see review by Coderre at al.45)." 
Terence Coderre
Reference 45 goes way back to a 1997 paper Coderre and Katz did together. Terence Coderre is a very busy man (who looks pretty young in this picture to have accomplished so much already.. obtained his PhD in 1985 and has published extensively ever since; here are the free ones). 

I came across his work a few years ago as I looked for papers to do with intraneural circulation. I noticed he was working out the biology of possible blood flow mediators in CRSP. Here is his paper about that, from 2009. Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management. 

But let's not become sidetracked that much peripherally. 
The next sentence in Melzack and Katz is
"Furthermore, it may be possible in some instances to prevent the development of central sensitization which contributes to pathological pain states." 
Well, heck yeah! 
My bold.

"The evidence that acute post-operative pain intensity and/or the amount of pain medication patients require after surgery are reduced by perioperative administration of variety of agents via the epidural46–48 or systemic route49–51 suggests that the surgically-induced afferent injury barrage arriving within the CNS, and the central sensitization it induces, can be prevented or at least obtunded significantly.52,53 "

Word for the day: "obtunded." Dulled, blunted, reduced level of consciousness,  usually used to describe level of awareness or consciousness of a patient in the context of head trauma. Hmmnn..

"The reduction in acute pain intensity associated with preoperative epidural anesthesia may even translate into reduced pain54 and pain disability55 weeks after patients have left the hospital and returned home."
"The fact that amputees are more likely to develop phantom limb pain if there is pain in the limb prior to amputation30 raises the possibility that the development of longer term neuropathic pain also can be prevented by reducing the potential for central sensitization at the time of amputation.52,53 Whether chronic post-operative problems such as painful scars, post-thoracotomy chest-wall pain, and phantom limb and stump pain can be reduced by blocking peri-operative nociceptive inputs awaits additional well-controlled clinical trials.56,57 Furthermore, research is required to determine whether multi-modal approaches may also prevent or relieve other forms of severe chronic pain such as post-herpetic neuralgia58 and complex regional pain syndrome. It is hoped that a combination of new pharmacological developments, careful clinical trials, and an increased understanding of the mechanisms underlying noxious stimulus-induced neuroplasticity, will lead to improved clinical treatment and prevention of pathological pain."
It makes complete sense that anesthetizing neurons, nerves, prior to surgery, would prevent a
whole bunch of all that crazy busy reactivity in the dorsal horn later, all the glia madly taking the opportunity of having become over-stimulated to set up all their excessive gap junctions for better communication, reversing anionic polarity so that inhibitory substances become excitatory instead, reving up all their genetic transcriptors to make piles more receptors than they really need or will ever need again, then all of that being too much work for them to take down later so they just leave it that way, because they're used to it now, like hoarders with yards full of rusted junk they've carefully accumulated that represents wealth to them, but just crazy behaviour to the neighbours who have to live alongside. 
Let's hear it for "obtunding" that first level of physiological processing in a system only 2 synapses away from becoming conscious awareness. So much easier than having to try to clean it all out after the fact.  

The next section is on pain and psychopathology. 


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!

1 comment:

Anonymous said...

Love this metaphor "yards full of rusted junk they've carefully accumulated that represents wealth to them, but just crazy behaviour to the neighbours who have to live alongside."

Still enjoying the journey Diane.
Thanks again,
Tim Cocks