Wednesday, July 17, 2013

Melzack & Katz, Pain. Part 14k: Glia calling glia, over.... Do you read?

The paper, Pain

Most recent blogposts:

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?)


Still carefully finding our way through the gliopathy paper. Still trying to get back to the Melzack&Katz paper. Yay us - we've made it all the way to the end of page 9, glial-glial interactions. It looks like a short section.. it's about how microglia and astrocytes bother each other in the spinal cord. Let's take a look:

Microglia to astrocytes:
  • Microglia make TNF-alpha. TNF-alpha stimulates astrocytes to activate JNK
  • Nerve injury makes microglia and astroctyes express IL-18, and IL18R respectively. (Should be IL18R1, I think, because there is no Wikipedia page for IL18R... [/sigh]). Anyway, the first one in microglia stimulates the second in astrocytes, which upregulates NF-KB which facilitates neuropathic pain. 
Astrocytes to microglia:
  • Cx43 (one of those connexin/gap junction structural protein thingies) becomes upregulated, cell figures out how to do paracrine signalling with it. Eyew - ATP and glutamate are made/released, right out into the extracellular space. Extracellular ATP is not good - it's implicated in a bunch of nervous system things associated with pain, like sciatic nerve entrapment, traumatic brain injury, spinal cord injury, inflammation. Not good. Not good at all. 
  • ATP activates P2X4, P2X7, P2Y6, and P2Y12 receptors in microglia. That can't be good... 
  • Astrocytic-CCL2 probably keeps microglial activation going.
  • Astrocytes make IFN-gamma - hello, microglial activation, probable neuropathic pain induction..
Also: Microglia and astrocytes can learn how to talk to themselves through autocrine and paracrine signalling. As if it wasn't bad enough they keep each other irritated... they make themselves crankier. This might be like having itchy mosquito bites, scratching them hard yourself because they're itchy, then they bleed and are still itchy anyway. 
  • e.g, bFGF becomes upregulated in astrocytes, then maintains astrocyte activation. 
  • late-phase MMP-2 upregulation maintains astrocyte activation and neuropathic pain - it cleaves IL-1beta, and helps phosphorylate ERK in astrocytes. So, yay about that. Not.

Anyway, that's what goes on in the dorsal horn. 

Next, what goes on in DRGs

If dorsal horns were like the shoreline between ocean of PNS and earth of CNS, rocky or smooth, then DRGs would be like submerged reefs just offshore, probably like coral reefs. 



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

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