Neonates and nociception

So, I'm feeling all queasy right now. And angry.
I've got to get this dealt with so I can continue studying in the cool online Pain Management Certification Program that started 7 weeks ago. 

All was well until I got to a fabulous lecture by a UBC OT, Liisa Holsti. I want to stress it is not her fault I've gone off-track and need to rant here for a bit. Not at all. In fact, her lecture is exemplary for being low-key and even-toned and academic and non-emotional and factual and supported by the literature, etcetcetc. She couldn't have presented anything more correctly or beyond reproach.

No, my anger is not at her, not even a bit.

The bile I can taste in my mouth has to do with all the stuff going on in the world that she is describing and studying. The fact that she has to study it in the first place. The fact that medical obliviousness to nociceptive capacity in full and preterm babies, in the first place, has led to such a socio-cultural adaptation of the medical system, that preemies get heel-poked 15 times a day, their little immature neural crest peripheral sensory neurons do their best but fail to handle all the stimulus successfully way upstream in time (because they aren't even developed yet!) such that downstream, after descending inhibition systems have hooked up, those descending systems have way more to deal with than they ever should have had. The fact all this came about a few decades ago all coincides perfectly with the chronic pain epidemic we're now in, and no one seems willing to point fingers at the iatrogenic components of it. It makes me very, very cross to learn about this; maybe I should have stayed ignorant. Wait, no, that's not usually a great way to be... so, for now, bear with me as I continue to swim, academic rope still between my teeth, into a large area (how large, I have no idea) that feels and smells a lot like culturally produced human cesspool.

Some basic factoids:

Image from http://www.frontlineint.com/

1. Humans are neotenous. We are born way early compared to other mammals and primates, whose nervous systems are developed enough to be able to move independently long before human systems are. We have to be, because our brains end up 5 times larger than the size usually required by mammals our size. If we stayed in the womb as long as it would take to be able to run around shortly after birth, our mothers' pelvises wouldn't be wide enough for them to successfully squeeze us out. The human/evolution compromise was to remain physically helpless a lot longer, dependent on a mom.
2.  Neural crest (sensory neurons, autonomic system peripherally, cranial nerves, glia, Schwann cells),  neural tube (brain, spinal cord) and epidermal derivatives (skin and sensory receptors) are like a three-ring nervous system circus; these three broad populations of cells that will eventually coordinate nervous system business arise independently from each other and don't braid together properly until at least a couple weeks after birth.  This is a critical window of time for a sensitive nervous system, and most of us just squeak by - with luck, no premature birth, and good careful responsive sensitive maternal handling, our sensory systems catch up without getting too overstimulated, without too much harm done. But... but....
3. What if we're born so young that all sorts of genius human primate grooming of the medical sort intrudes itself on our fragile little systems? Think about it. (I did and my mirror neurons made me want to scream and go fight somebody.) Think of a baby this tiny getting poked in the heel as many as 15 times a day.
4. Sensory neurons are present in an embryo on day 12 - DAY 12! of gestation. In gestational week three they already start to hook up to the spinal cord. C-fibers, which can't carry as much information and have a higher threshold if they are nociceptors, don't hook up in the spinal cord until 5 days after a normal term delivery. This means that the fibers nature provided us with, to convey nociception, are lagging behind actual nociception, and big fast accurate sensory fibers that are supposed to carry ordinary sensation have to carry, and are being sensitized to, inappropriate (for them) noxious stimuli instead. An analogy might be something like child rape - a human system is forced to have to endure something long before it's ready. (Maybe that's what's so sickening here. This analogy bothers me even though it's an appropriate one - the very existence of child rape makes me feel exactly the same, like I want to plow somebody in the face.)
5. The brain isn't fully grown up until the third decade of life. It can feel noxious stimulation  (Slater et al 2006; Bartocci et al 2006) - but it can't do anything about it yet. How much does that suck? This is all evolutionary hangover. The peripheral nervous system and spinal cord evolved before the brain did. Tough darts - that's just the way it turned out. Now human embryological development is stuck with it.
6. There is a surplus of neurons present at birth. More bad. They get pruned by a few weeks postnatal, but until then, it would be better not to rile them, because they can totally sculpt and script a bunch of cord plasticity, and not in a favorable way. Argh! Sigh. 
7. The system is more excitable than inhibitory, the receptive fields are much bigger, skin is thinner with (excess) sensory neurons right out to the edge of it ("hyperinnervation"), and look at the relative size! (see picture). A baby heel is much tinier, plus it's packed with 20% more large sensory neurons, sensory neurons that can "feel" all sorts of stuff but are in a system that still doesn't have anywhere "absorbent" to receive their overstimulated info into! So all that nociceptive noise goes into the spinal cord, dorsal horn (the very very innocent and undeveloped and as yet incapable dorsal horn), up dorsal columns too, maybe, some of it, and the reverb in there is terrible. The dorsal horn can't contain it and it just echoes around, spreads all over the place to lots of other inappropriately receptive spinal segments, scuplting the system as it goes, because the system is oversensitive AND undermature.
8. Yeah, I realize that a preemie might die without all the medical attention. I realize anxious helpless-feeling parents want and need all the help they can get from whoever they can get it from. But I gotta say, if I were a preemie nervous system, I'd want to tell the world to butt out, let me snuggle with my mom for as long as I could and let me die (if that's what the future had in store), relatively happy - I would not want to face a great long human life span with a nervous system that had been primed by well-meaning but blundery medical intervention to potentially hurt me for the rest of what could be a long and otherwise fairly healthy life. What about my sad parents? Well, yes, all this would indeed be sad for them, but they are the supposed adults, my life isn't supposed to be a sacrifice for them - I didn't ask to come to endure it, they invited me to their party, and I should be allowed to leave if I can't find it put-up-withable. Shouldn't I?

Nov 8 Postscript:
I'm back in this post today to let people know I'm over being angry, and back to merely being depressed about this and about the over-all medical, business-as-usual assumption that babies feel less pain/feel pain less because they are underdeveloped.

I'm over it. What makes me ongoingly, grindingly, perpetually mad, mostly, in PT or medicine or anything else to do with health care and its delivery, is the observation that people seem to easily give over their own primate-given ability to use good sense and sensitivity, to mindless human  protocolization, what I call "zombification" of treatment, through wrong-headed reliance on or worship of "standardization". In my opinion this makes the working grind easier on people but at the same time I think it dulls people to the feelings of others, of patients - it really does. It makes them do things in a ritual way rather than in a way that would connect them to that patient's process, or if it seemed to be "nocicepting" somebody, decide to not do the thing at all or figure out a way to do it that doesn't hurt. And what do humans have an abundance of? Love for ritual for the sake of ritual. That's REALLY what P's me off, but about humans in general, and about the way the working world turned itself into factory and then the hospital world turned itself into a caricature thereof. I don't know how to deconstruct that, but I hate the feel of it, always have. Poor wee babies. 


Nov. 12: Another postscript: This just in: Reducing Neonatal Pain during Routine Heel Lance Procedures by Carla Morrow et al. 

Abstract

Purpose: To measure the difference in pain scores for newborns who were held and swaddled while undergoing routine heel lance procedures compared to newborns who were lying on their backs and not swaddled during heel lance. Additionally, we sought to compare the total amount of time it took to collect the specimens in each group.

Design and Methods: A total of 42 neonates recruited from a large tertiary hospital were enrolled in a randomized controlled trial. Infants in the experimental group (n = 22) were swaddled and held in an upright position during routine heel lance procedures while neonates in the control group (n = 20) remained in a standard care position. Pain was measured with the Neonatal Inventory Pain Scale (NIPS) at two points in time for each group (just before the heel lance procedure and at the completion of the heel lance). Total collection time was measured using a stopwatch accurate to 1/100th of a second. Specimen quality was measured based on the number of rejected specimens for each group. Descriptive statistics and t tests were used to analyze the data.

Results: The mean NIPS score for neonates who were swaddled and held during the procedure (experimental group) was significantly lower (M = 1.3, SD = .9) than the score for infants in the standard position (control group) (M = 2.7, SD = 1.3), t (40) = -4.48, p < .001. Although the total collection time was lower for infants who were swaddled (2 minutes and 17 seconds, SD = 59) versus (2 minutes and 47 seconds, SD = 85) for controls, this was not a statistically significant difference (p = .45).

Clinical Implications: Swaddling combined with positioning neonates upright during routine heel lance procedures offers nurses a nonpharmacologic method of neonatal pain reduction for heel sticks. This technique can be easily implemented on any unit independent of facility protocols. Furthermore, the technique is not associated with any cost or policy development, making it more likely that nurses can use it in practice.

I found it here:  Hold the patient; help the pain?
(Nice. It still makes me shake my head, however, at what strange versions of primates we've become as humans that we have to bother constructing expensive research to prove to each other/funders/medical business-as-usual that something as simple as holding a (likely) existentially-terrified (anyway) baby will have it register less noxious stimuli or reactivity by holding it. Sheesh... other primates would likely already have this all figured out - instinctively.)

Unfoldment of a zebrafish

Mo at Neurophilosophy has a new post containing movies of the embryologic development of a zebrafish, with links to the site they come from. Great find Mo, thanks.

I love the spherical expansion, then that sudden whoosh into something that has two sides to it.

This is how vertebrate embryology is studied, and humans are vertebrates, so it's how we unfold too.

The Fish With Arm Bones

Tiktaalik rosae is the name Neil Shubin's team gave a fossil they found in the Canadian Arctic a couple years ago. Shubin's book, Your Inner Fish, describes the dig and the excitement that surrounded the discovery of what Shubin calls a "fishapod".

The book is a great read - full of evolutionary and embryologic connections. You'll learn where spines and skeletons come from, what genes we share with our insect and worm relations, why hernias and knee injuries have come to plague the human species. You'll learn all about how gill arches turned into inner ear bones and throat cartilages, how head bones form, why the development of a mobile neck (present in Tiktaalik) was a revolution in evolution (it freed the upper limbs to do one thing while the head did another).

I was hoping for a fuller examination of the evolution of the nervous system, but alas, such an examination was beyond the scope of this book apparently. There are a few tidbits on brainstem function and central pattern generators, and why the phrenic and vagus nerves emerge so soon and dangle dangerously outside the spinal column before reaching their destinations.

It is hard to put this book down if you have any sort of interest in the human body, whether it is a third-person or first-person interest. It will leave the reader feeling an integrated part of all nature through time. I recommend reading it together with Into the Cool (much of which is available free online in the link provided) and dazzle gradually, both of which are co-written by Dorion Sagan. For more about the evolution of the nervous system itself, Up From Dragons is a fairly good read, yet another Dorion Sagan co-write. (How can you tell I'm a big Dorion Sagan fan?)

Adrenal Cells and Pain

Kevin McHenry's latest blog is on chomaffin cells and the relationship they may have to reducing pain. In there he mentions their "strange affinity" with neurons. He marvels that with the addition of "a little acid", chromaffin cells can be made to turn into neurons.

Perhaps this is not so strange when we remember that they are close relatives, coming as they do, embryologically, from neural crest. Anything made after mesenchyme splits off (to make mesodermal derivatives like bone, muscle, joints, connective tissue, which create structural support for an organism and use way less oxygen) ... anything made after the mesenchymal layer splits off is likely to have a higher "access code" to the nervous system proper than anything mesodermal, and enjoy a closer relationship.

Neural crest makes the entire peripheral nervous system - not motor axons, but all the sensory neurons including dorsal root ganglia, and all sympathetic nervous system related structures like chromaffin cells.