Friday, March 08, 2013

Nociceptive musings

Ordinary existence in the micromilieu
based on image from Textbook of Pain

All winter I feel I've been immersed in the peripheral nervous system. Here is a picture I made, based on an image from Textbook of Pain, which depicts the interrelationship of:

1. (potentially nociceptive) afferents (which live most of their lives minding their own business, providing trophic factors to whatever they happen to be plugged into, not "nocicepting", unless or until something disturbs their peaceful (if ordinarily quite dull) existence;

2. sympathetic efferent neurons, whose job is to take over in a crisis - constrict vascular lumen size (if they go to hypodermis or viscera) and enhance blood flow to muscle "by as much as 1200%(if they go to muscle - not depicted in this particular image) and lung;

3. vasculature, particularly the tiny stuff, the bottom of the system, where we can hardly tell what is arterial and what is venule anymore, because the vessels are so small, and capillaries don't care one way or the other - they just sit there and let the blood flow however it wants, through capillary action, because their job is to be as barely there and thin and leaky and passive as possible so that the red blood cells can  a...l...m...o...s...t  touch what is outside the physicality of the blood flow system, and let their oxygen cargo and maybe immune cells and other things escape into/ be downloaded into tissue space and by outside cells, part of whatever tissue they are feeding. 


Life from a nociceptor's point of view

"Hi there. I'm a single long skinny cell. My name is "C" - "C" is for Cell. At least that's how I like to think about it. I'm the same as any other cell, just a lot longer and a lot skinnier, which means I have a lot more surface area compared to volume, compared to short spherical cells, which in and of itself makes me more "sensitive" ... relatively speaking. 
"There are lots of us C's, and we do different things - some of us are around to look out for trouble and kick up a fuss if we notice any. We are called "nociceptors."
"But truth is, it takes a lot to bother me. I have what I need in life - a place to live that's warm, enough to keep me alive, a job to do that isn't very hard - most of it is about ingesting then excreting (which is what all creatures do, regardless of their size - when it's a cell, this is usually called secretion, rather than excretion, but really, it's all the same thing when you take a close look.)
"I have one really really long arm, and one that's much shorter. My head lives in a special zone called the dorsal root ganglion, along with a bunch of other heads of other cells. Which is great, because we can talk about all kinds of stuff in there, to each other. Kind of.
One of my arms is very long. For example, I can span the distance of somebody's big toe, all the way up as far as the DRG, then with my short arm into the dorsal horn of their spinal cord - my short arm ends there, and some other second order neuron takes delivery of my information to places I don't have a clue about. Much of the time I have no idea if delivery even made it past that point. Whatever. I don't need to know what goes on any further up the track. My job is to do the best I can with the little arm and the long arm I have. I have non-nociceptor cousins whose second arm is a lot longer than mine - they can reach right up into the brain! Those cousins are much fatter than I am, too.
"People often describe me as unmyelinated. That's not really true. I have a coat. It's thin, and I have to share it with a bunch of other C's, but I have one, and it's a Schwann cell. My thicker relatives have thicker coats, and in fact, they can have several coats each. It's kind of not fair in a way; however, they are way more sensitive than I am, and their coats sort of protect them from the big dark warm wet world we live in with all its biochemistry. When I think about it, I'm kind of glad they have thick coats, or else they might bother me a lot more with all their low-threshold-i-ness.
"My closest sibling is ADelta. Even though our jobs are quite a bit alike, ADelta is a bit thicker, faster, and has a coat more like those low-threshold types. ADelta can often get messages upstairs a lot faster than I can.
"One thing I can do that ADelta can't, is I can make venules leak. It's something I can secrete or excrete, that ADelta can't. Why would I want to? I don't really know, it just happens... I'm "peptidergic."
"Lots of people blame me for pain. It's not true. I'm not responsible for anything that might happen upstairs. It's like blaming the guy who loads boxes onto a truck for the entire response of recipients who end up with what's in the boxes, and may not know what to do with it. Or maybe for the hairballs their cats who play inside the boxes after they've been emptied cough up...  I mean, it's not fair, right? I realize I play a small role, but hey, pain is not really about me. After that truck leaves the loading dock, anything that happens after that is not really my problem. So stop blaming pain on me. OK?"
Nociceptive musings2

Nociceptive musings3

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Nociceptive musings 6

Moseley L; Teaching people about pain: why do we keep beating around the bush? Future Medicine, January 2012, Vol. 2, No. 1, Pages 1-3

"We tend to endorse the complexity of the brain and its fundamental role in what we experience. Unless, of course, we are talking about pain.Some 25 years ago, Patrick Wall, as frank a communicator as any, lamented the trend towards beating around the bush when it comes to pain: “The labeling of nociceptors as pain fibers was not an admirable simplification, but an unfortunate trivialization under the guise of simplification” [1]. Of course, equating pain to activity in nociceptors is seductive – nociception and pain seem so tightly coupled. However, are nociception and pain really so tightly coupled? This issue was actually settled a couple of decades ago – there is not an isomorphic relationship between pain and nociception, nor between pain and tissue damage... Meaning is a very potent modulator of the relationship between nociception and pain. Indeed, one might argue that meaning is the critical determinant of pain, because if a nociceptive input is not evaluated by the brain as reflecting a threat to body tissue, pain would clearly be an erroneous output, serve no survival function and offer no evolutionary advantage...Real-time modulation can involve neurally, neurochemically or humorally driven alteration of the response profile of neurones within the nociceptive neuraxis. So, the mislabeling of nociceptors as pain fibers was indeed a trivialization, but was it really that unfortunate? I contend that one need only look at the huge burden of chronic pain to uphold a resounding ‘yes’... Yet we continue to avoid the truth that tissue damage, nociception and pain are distinct. I would go so far as to suggest that even the use of these erroneous terms – pain receptors, pain fibers and pain pathways – leaves the patient with chronic pain feeling illegitimate and betrayed, and leaves the rehabilitation team lacking credibility when they look beyond the tissues for a way to change pain."


BronnieT said...

GREAT explanations Diane! I'm passing this onto my postgrad students who are just touching on neurobiology in this part of the semester.

Diane Jacobs said...

Thanks for your comment, Bronnie.