Tuesday, January 17, 2012

Longterm potentiation and nociception

As I scanned through Edge.org's question for 2012, I came upon this: Todd Sacktor's essay on "Elementary Particles of Memory", his contribution to the question,  2012: What is your favorite deep, elegant, or beautiful explanation? 


Excerpt:
The key molecule maintaining LTP is a persistently active enzyme, called PKMzeta. Together with the molecules maintaining LTD that are still being determined, these elementary molecules store most forms of memory. Without the persistent strengthening of synapses by PKMzeta, the ongoing physiological process of LTP at the synapse collapses, and most long-term memories are erased. The animal returns to a "blank slate," with just its genetic inheritance of behavior.
LTP= longterm potentiation. It's a process by which synaptic connections between neurons are strengthened. 
LTP is a persistent strengthening of synaptic connections triggered by a brief episode of high-frequency activity of those connections... The key molecule maintaining LTP is a persistently active enzyme, called PKMzeta... PKMzeta is an unusual form of protein kinase. Once made when LTP is triggered, PKMzeta is active all the time, rather than being turned on and off in response to other molecules. When mutations occur in genes for kinases that render them active all the time, they promote uncontrolled growth in cells, leading to cancer. However, the change in the gene that encodes PKMzeta also restricts the formation of the persistently active kinase to neurons. Because mature neurons are tethered to thousands of other neurons through their synapses, they cannot possibly divide and are remarkably resistant to forming cancers (most brain tumors in adults originate from glial cells, which readily divide). By restriction to cells that communicate but cannot divide, a mutation signaling continual growth, potentially deadly to an organism, was used to maintain long-term memory.
Isn't that remarkable. Here is a paper by him, from 2008: 

PKMzeta, LTP maintenance, and the dynamic molecular biology of memory storage.

ABSTRACT: How memories persist is a fundamental neurobiological question. The most commonly studied physiological model of memory is long-term potentiation (LTP). The molecular mechanisms of LTP can be divided into two phases: induction, triggering the potentiation; and maintenance, sustaining the potentiation over time. Although many molecules participate in induction, very few have been implicated in the mechanism of maintenance. Understanding maintenance, however, is critical for testing the hypothesis that LTP sustains memory storage in the brain. Only a single molecule has been found both necessary and sufficient for maintaining LTP--the brain-specific, atypical PKC isoform, protein kinase Mzeta (PKMzeta). Although full-length PKC isoforms respond to transient second messengers, and are involved in LTP induction, PKMzeta is a second messenger-independent kinase, consisting of the independent catalytic domain of PKCzeta, and is persistently active to sustain LTP maintenance. PKMzeta is produced by a unique PKMzeta mRNA, which is generated by an internal promoter within the PKCzeta gene and transported to the dendrites of neurons. LTP induction increases new PKMzeta synthesis, and the increased level of PKMzeta then enhances synaptic transmission by doubling the number of postsynaptic AMPA receptors (AMPAR) through GluR2 subunit-mediated trafficking of the receptors to the synapse. PKMzeta mediates synaptic potentiation specifically during the late-phase of LTP, as PKMzeta inhibitors can reverse established LTP when applied several hours after tetanization in hippocampal slices or 1 day after tetanization in vivo. These studies set the stage for testing the hypothesis that the mechanism of LTP maintenance sustains memory storage. PKMzeta inhibition in the hippocampus after learning eliminates the retention of spatial memory. Once the PKMzeta inhibitor has been eliminated, the memory is still erased, but new spatial memories can be learned and stored. Similar results are found for conditioned taste aversion when the inhibitor is injected in the insular neocortex. Thus PKMzeta is the first molecule found to be a component of the long-term memory trace.

Hmn. Insular cortex. That little brainpart, important in pain processing, in salience processing, shows up again. 
Anyway.
So... find something that messes with LTP and maybe.. "memory" could be erased? ... but I am way ahead of myself. Let me start again. 

A few days ago, this story came out of Nature | News: High-dose opiates could crack chronic pain. People in Vienna have found a way to reverse longterm potentiation in spinal cord synapses, at least in rat models. Here is the abstract of their paper,  Erasure of a Spinal Memory Trace of Pain by a Brief, High-Dose Opioid Administration:
Painful stimuli activate nociceptive C fibers and induce synaptic long-term potentiation (LTP) at their spinal terminals. LTP at C-fiber synapses represents a cellular model for pain amplification (hyperalgesia) and for a memory trace of pain. μ-Opioid receptor agonists exert a powerful but reversible depression at C-fiber synapses that renders the continuous application of low opioid doses the gold standard in pain therapy. We discovered that brief application of a high opioid dose reversed various forms of activity-dependent LTP at C-fiber synapses. Depotentiation involved Ca2+-dependent signaling and normalization of the phosphorylation state of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. This also reversed hyperalgesia in behaving animals. Opioids thus not only temporarily dampen pain but may also erase a spinal memory trace of pain.
So, what they did was, took rats, gave them 'chronic pain', i.e., allowed longterm potentiation to develop in their spinal cord synapses such that the second-order neurons conveying nociceptive afferent information to the rats' poor little brains, presumably their insular cortices, along with some other destinations probably, got way better at their jobs. Then, the researchers figured out what dose, and what kind, of opioid it took to reverse all the longterm potentiated changes. It turned out to be something called remifentanil, a "potent ultra short-acting synthetic opioid analgesic drug",  "given to patients during surgery to relieve pain and as an adjunct to anesthetic."

(A bit further down in the Wikipedia link is this interesting comment: 
Doses listed in the package insert from its manufacturer are much higher than those used in actual clinical practice
Huh. Gee, why not use it according to directions?)

Yes, pain would be a good thing to be helped to forget. Great place to start. 

There are only three neurons between anywhere on the surface of a vertebrate (or beneath its surface, I suppose..), and said vertebrate's brain. Clearly the junctions are the right place to target. Clearly opioids can help with pain, both prevention and, apparently, according to this, cure. It looks as though Sacktor may have been looking at the second link in the chain. The Vienna people looked at the first link.

I looked in the Vienna paper to see if PKMzeta figured in at all - the authors say they took a look:
We thus asked whether PKMz in spinal cord also plays a role for the maintenance phase of LTP (22, 23) after LFS. PKMz inhibitor ZIP had, however, no obvious effect on the maintenance of LFS-induced LTP within the observation period of 6 hours (fig. S2D).
22. M. N. Asiedu et al., J. Neurosci. 31, 6646 (2011).
23. T. C. Sacktor, Nat. Rev. Neurosci. 12, 9 (2011).
 It looks like they didn't see what Sactor found, or else they found something else:
Depending on the type of conditioning stimulation, distinct forms of LTP [longterm potentiation] are induced at C-fiber synapses, which affect different groups of postsynaptic neurons (13, 24) and involve signaling pathways that overlap only partially (13, 24, 25). 
We therefore tested whether OID [opioid-induced depotentiation] can also be achieved for other forms of established spinal LTP. We induced LTP by conditioning high-frequency stimulation (HFS, 100 Hz; fig. S3A) of sciatic nerve fibers or by subcutaneous capsaicin injections (fig. S3C). 
The latter selectively activates nociceptive nerve fibers, which express the transient receptor potential channel subfamily V member 1 (TRPV1). Remifentanil also fully reversed these forms of LTP (after HFS,  depotentiation was from 158 ± 8% to 99 ± 9%, n=12,P<0.001; after capsaicin,  depotentiation was from 170 ± 16% to 100 ± 13%, n=5, P<0.001;fig.S3, B and D), demonstrating that OID applies to various forms of activity-dependent LTP at C-fiber synapses.
My comments inside square brackets.

It's probably worth mentioning that if that first synapse, the one in the dorsal horn, can be affected, then the second-order neuron, the one that not only carries the info straight up but can turn into a signal amplifier blasting the info through the thalamus into all the third-order neurons that go to the sensory cortex, insular cortex, anterior cingulate cortex, like a lawn sprinkler on steroids, or a finger over the end of a garden hose increasing the distance and force of the spray, will be diminished to mere leakage. Then the brain will be able to ignore the ordinary light tapping or tinking of rain (nociception) on the roof, instead of a continuous thunderous pounding driving rainstorm day in and day out. Yes, one could still distract oneself (not register it as "pain") but it would probably be a lot harder than if the noise level could just be turned way down again to ordinary levels.


From the Viennese paper:
LTP is a synaptic model for some forms of hyperalgesia (26). We therefore asked whether OID has any relevance for behaving animals. Sub- cutaneous injections of capsaicin quickly led to mechanical hyperalgesia at the injected hindpaw (Fig. 4). The same dosage regimen of remifentanil that caused OID significantly attenuated capsaicin- induced hyperalgesia (Fig. 4A). Not surprisingly, the behavioral hyperalgesia was reversed only partially by the opioid treatment because additional peripheral and central mechanisms contribute to capsaicin-induced hyperalgesia (27, 28). PP1 inhibitor calyculin A fully blocked the attenuation of hyperalgesia by remifentanil (Fig. 4B), suggesting that depotentiation at nociceptive C fibers may erase a memory trace of pain[sic - at this point it's still only nociception]. LTP is expressed in ascending nociceptive pathways, which are relevant for the aversive components of pain. It will thus be interesting to explore whether opioids may also reverse the tonic-aversive state of pain (29). Taken together, the present and our previous data (3) demonstrate that activation of spinal MORs triggers distinct, bidirectional, and state-dependent synaptic plasticity in naïve versus potentiated C-fiber synapses. Remifentanil activates Ca2+-dependent signaling pathways, leading to activation of PP1 and PKC. At potentiated synapses, this normalizes the phosphorylation state [i.e., reverses the energy efficiency gained, makes them work harder again, makes them more "naive" again] of GluR1 at Ser831 and that of GluR2 at Ser880 and thereby depotentiates synaptic strength in C fibers. The presently identified reversal of synaptic LTP in nociceptive pathways provides a rationale for novel therapeutic strategies to cure rather than to temporarily dampen some forms of pain with opioids.
All "synaptic learning" seems to be about, really, in the case of pain, is a ratcheting of energy efficiency, such that the nociceptive neurons take advantage of a chemically altered "gain" in synaptic "strength" so that they can do their job with less fuel, perhaps. Economy of means. The Vienna people have figured out how to reverse that in a rat model, at the first synapse: it seems to me that Sactor's work has had to do with the second synapse upstairs in the brain, that he has not directly involved himself in LTP of the nociceptive system. 


Anyway, those are just some ramblings I've strung together from two recently read pieces of work that sound like maybe they talk about the same thing, LTP, but when I look close, I can't see that they actually do. I need to read the Vienna paper several more times, but so far it still looks like there's a gap between pain science and other neuroscience. It might help if people doing 'pain' science at the first synapse would stop calling it "pain science" and instead would call it "nociception science."



Friday, January 13, 2012

"Robert Trivers: Why do we deceive ourselves?"

Robert Trivers explains deception at many levels, psychosocial and biological. Favorite takeaway line:

"Men tend to be more overconfident than women do. Both of us tend to be overconfident, in various circumstances, but it's more a male disease. So powerful men are both overconfident, and ignorant. That's an unfortunate combination." 

http://fora.tv/2011/10/04/Robert_Trivers_Why_Do_We_Deceive_Ourselves

Sorry, I don't know how to embed this. You will need to copy and paste the url. Please do - it's great, about 16 minutes.

Thursday, January 12, 2012

To be brutally honest..

I'm only 5'2". I gained weight, for years. I did not "feel" too fat.

When I looked at myself objectively, I could "see" that I was "fat".
Deciding to start losing it was a conscious decision. I did not firmly decide to lose weight until I saw I had reached about 190 pounds. The weight of many hefty, bossy, alpha type men. I took some time, but knew that enough was enough, and I'd have to start to rescue myself from the danger of potential deliberately engaged ill-health. Just like I quit smoking at age 30-ish, just because it was time.

I did not weigh myself, almost my whole life. I did not restrict eating. I ate whatever I wanted. Whatever quantity I wanted. Whenever I wanted. I started doing this with no restriction at the end of the eighties, just as I was facing the end of my "youth" and turning 40. Prior to that, I had restricted myself somewhat in order to "look good" (well, as good as it was possible for me to look without trying very hard).

Restricting myself just in order to "look good" began to feel very artificial, very much a constraint I imposed upon myself due to external priorities, only, not because I really wanted to.

I think I must have thought, when I reached midlife, "It doesn't really matter anyway - who do I think I'm trying to impress by being "normal"? "
I deliberately did that socially unacceptable thing called "letting oneself go", and flipped my chin at the whole idea that other peoples' opinion would constrain me: some new part of me started to fight for autonomy: I started gaining weight, dropped external constraint, got to know "me", opened a practice of my own, became an adult, lots of stuff all at once. I went through midlife crisis, menopause, felt awful, felt like I was whitewater rafting almost every day, still functioned in the world.

Getting "big" did not happen overnight. Getting on the internet helped me sit still, which helped a lot. I think I had got my biggest by about 2007.

To be honest, something in me liked weighing a lot. Something about me liked having mass. Something in me liked having gravitas. Something in me definitely liked having a bit of weight to throw around. (See recent blog post about posture and anger and dominance.) Completely subjective of course - I could have been knocked over with a feather, probably. But I felt quite strong, never felt handicapped. I proved many things to myself, by being a fat person for a long time.

1. My weight did not really interfere with my life. It has been a successful life, lived entirely on my own terms.
2. My weight reassured me that I was real. Had substance.
3. My weight never stopped me doing anything I wanted to do. Mind you, nothing I wanted to do was ever particularly physical to begin with.
4. Even though I was never very physical, I was always active; therefore, I think I stayed healthy.

All of this is occurring to me, only now that my weight has dropped by another 20 pounds or so.
Part of me is grieving a bit because it wanted to be "big". But, alas, I can't be "big" and stay healthy in the long term, at the same time. I'm just not tall enough.

To be brutally honest, what I learned from being objectively, medically, dangerously, however-you-want-to-define-it fat, or big, was a new boundary, and some kind of internally derived and sensed power, or sense of self.

Wednesday, January 11, 2012

"It hurts when I do this (or you do that): Posture and pain tolerance"

I linked to this paper earlier this week on Facebook (link to Facebook thread) because something about it made me stop and think.
Abstract: Recent research (Carney, Cuddy, & Yap, 2010) has shown that adopting a powerful pose changes people's hormonal levels and increases their propensity to take risks in the same ways that possessing actual power does. In the current research, we explore whether adopting physical postures associated with power, or simply interacting with others who adopt these postures, can similarly influence sensitivity to pain. We conducted two experiments. In Experiment 1, participants who adopted dominant poses displayed higher pain thresholds than those who adopted submissive or neutral poses. These findings were not explained by semantic priming. In Experiment 2, we manipulated power poses via an interpersonal interaction and found that power posing engendered a complementary (Tiedens & Fragale, 2003) embodied power experience in interaction partners. Participants who interacted with a submissive confederate displayed higher pain thresholds and greater handgrip strength than participants who interacted with a dominant confederate.
My comment there was, "Huh! Non-nociceptive induction of pain. I like the psychosocial angle this paper takes. Strictly visual signaling can sensitize the salience or threat detection system. If this is valid and that's the case, is it any wonder that women seem to have more chronic "pain" than men?"


Chronic pain is experienced by more women than men. Pain is experienced differently by women than it is by men. Pain experienced by people less advantaged socioeconomically is experienced as more disabling. Women are generally less advantaged socio-economically.   


The idea of considering a "salience" system, as opposed to a "pain" system, is important. One of my favorite papers of all time is The pain matrix reloaded: A salience detection system for the body, by Legrain et al, who argue that if a wasp comes toward you and you think it's going to sting you, you will instinctively try to swat it prior to any nociception ever having had to occur. 


Here is the entry for "dominance" in the non-verbal dictionary at Center for non-verbal studies (a great link, by the way - hours of fun and learning.)


An external dominance display travels immediately to the threat detection system via the visual cortex, and the salience network notices. If it's an internally generated dominance display, i.e., one produced by the organism itself, the salience system gets the news via other channels maybe, gets the idea that all is well, I guess. Check out Todd Hargrove's blogpost, Posture and Pain Tolerance, about the same paper. Todd says, 
In the first experiment, participants who assumed a dominant posture displayed higher pain tolerance than those in submissive postures. 
In the second experiment, subjects had differing strength and pain tolerance levels depending on whether they interacted with a partner who used either dominant or submissive posturing. 
For example, if a subject was paired with a partner with dominant body language, this encouraged the subject to adopt a submissive posture in response, which made him weaker and less pain tolerant. 
Remember this next time you hire a buff alpha male as a personal trainer.
My bold.
As a PT, I was taught "good" posture, to be on the lookout for "bad" posture, and to try to "correct" the posture of almost every patient who came to see me. This was going to help them, or so I was led to believe. Not that "poor" posture actually caused, or correction thereof ever really fixed, any actual pain problems. Lots of people with already "good" posture had lots of pain too. To me, this story about psychosocial aspects of posture and pain absolutely destroys "misbehaving meat" heuristic conjecture about posture&pain, entirely.

The whole thing about our being primates is very relevant: as a short female human primate my psychosocial reality is I've been physically subordinate to most people all my life. What I've learned recently about personally inhabiting this kind of humanantigravitysuit, especially as it ages, is that anger is useful against, can even vanquish entirely, pain. (Pain associated with frozen shoulder at least.) Maybe an interoceptive, turned-inward sense of anger naturally builds from frustration of life lived in a world full of taller, and therefore by visual default, more (potentially) dominant people; if extraverted perhaps it turns into short man syndrome, or small dog agression. Perhaps anger is valuable for maintaining a sense of well-being, on an organism level. Clearly subordinate individuals must have to suppress most outward display of any internal anger they may have if they don't want to be killed by the rest of the troop or pack, or in the case of humans, separated from one troop and put in jail with another kind. Clearly humans have to learn how to find inner strength, yet remain humble, remain harmless, remain interactive.  Most figure it out one way or another. 
As a therapist, I never go there. Wading into peoples' feelings. As a therapist, I do not encourage expression of emotion. (I don't suppress it if it comes up, but my kind of therapy has nothing to do with trying to elicit it in others.) I do not want to be in anyone's line of fire; I grew up with a physically abusive (at times) mother, and was attacked once by a very cranky dachshund who dashed out of his yard through his gate at me, while I innocently walked by his house, on the public sidewalk. I've spent a lifetime dealing with, dancing with, trying to understand and harness anger, in myself. I do not want to deal with it in other people in any way whatsoever, especially not as a therapist. Yet, wow. I discovered my own anger to be so extremely useful, so ready to help me, when I had horrid pain. And I found it relatively easy to engage and use effectively in the presence of a therapist, without freaking her out.  So I guess my opinion is, save it til you really need it for something. 


To women, on a biological level, and on much.. OK, most of the human psychosocial level, it's a man's world. Yet.. 
This morning as I rode the elliptical, in front of the movie, Australia, which I've now seen 30-minute chunks of often enough to be able to remember them better, a thought crossed my mind during the scene where Drover arrives unexpectedly to the ball, just as Lady Ashley is right on the brink of signing her cattle ranch over to the appropriately-named robber cattle baron, Carney; "Drover" (the dashing male lead played by flashes-his-12-pack-during-the-movie Hugh Jackman)  who apparently cleans up well, appears at the top of the stair all decked out in a (impossibly!) perfectly tailored suit, just in the nick of time to save the day, the ranch, the lady, and have a bit of inner revenge on the snob bunch by impressing them all with his looks and ability to fox trot after only one drunken lesson out on the range. 
For the one and only time in the whole long movie, he is completely clean-shaven. 
Interesting (I thought as I huffed and puffed): men who shave appear much less dominating to female human primates; men who want to get close to women, without intimidating them by default, shave their faces. They try to make themselves look more like us. I've read there are fish that do the same thing, mimic the appearance of girl fish, and end up mating, having more offspring, or something. It even has a name: inter-sexual mimicry. 






Sunday, January 08, 2012

Yogawareness

Recently NYT published an article to do with yoga: How Yoga Can Wreck Your Body.
Paul Ingraham, at SaveYourself.ca, linked the article on Facebook as did several other people, but somehow Paul's threads always seem to end up being a well-attended party, so here is a link to it: Paul's SaveYourself.ca thread about the yoga article. 

The very first blogpost I ever wrote here was about this very topic: Mourning yoga, October 2005. The tide would seem to not yet have turned, if the New York Times is now feeling obliged to write about yoga injury..

Maybe this will help - a piece from the Guardian sent to me this morning by Ian Stevens, an old online friend who lives in Scotland: Prepare the mind.

It contains five useful preparations:

1. Intention:

"Physical exercise begins before you start moving – with intention. Understanding the function of the exercise, preparing the body, being confident in the required breathing, timing and form, and then committing yourself. After all, if you're not sure where you're going, and how you're going to get there, then you're unlikely to reach your destination. So train smart. Take the time to prepare mentally before each and every exercise. It will ensure a safe, enjoyable, effective workout – maximum benefit, minimum time."
Oh my gosh. Yes. If it's yoga, know that there is no goal at all. None. Just easy expansion, or contraction, in any and all positions, like a sea creature. Working ever so gently toward being able to do that effortlessly. Being able to feel as though gravity is canceled out of your humanantigravitysuit and you are weightless, floating in the universe, physically part of it (you are anyway, whether you acknowledge it or not).

2. Breathing:
"During exercise, the muscles in the body require oxygen to create energy. The breath is crucial in exercising efficiently and effectively. A lack of oxygen will lead to tiredness, tension and even nausea; sufficient oxygen means peak performance and that feeling of being energised. So, take a deep breath at the start of each exercise, then focus on steadily exhaling as you complete the more strenuous phase, and steadily inhaling as you complete the less strenuous phase of the exercise. Whenever possible, avoid holding the breath while exercising. "
I would propose that deep breathing does a LOT more than just "provide the muscles with oxygen." Sure, it does that, but it provides the brain with oxygen too: Furthermore, it expands and contracts the entire trunk, raises and lowers the diaphragm. For sure it will "slide&floss" phrenic nerve roots in the neck, the thoracic spinal nerves within the meat around the ribs, and all the long cutaneous lumbar nerves flowing between and through body wall layers of the low back, pelvis, abdomen, and inguinal fold. Furthermore, deep breathing will change the chemistry of the body a little, which will affect how brainstem nuclei E-ffect E-verything E-lse. Including any sense of anxiety one might start out with. Never ever hold your breath.
3. Timing: 
"Timing in exercise means being fully aware of your rhythm. Each type of exercise has its own natural tempo – some are best performed fast, some slow, steady and deliberate. Timing is often related to the amount of effort we put into the exercise. Try to leave behind robotic, tense movements, and develop a natural, flowing style, like a top tennis player in action. An exercise performed with the right timing will always be more effective than one that is rushed. So focus on the rhythm of each exercise, using the breath to help you."
... And some "exercise", like yoga for example, is best done with no speed whatsoever. It should be done as though you had all the time in the world. It should be done completely outside of mere time.
 4. Form: 
"Good form ensures exercise is done through the entire range of movement, targeting every part of the muscle, in the most efficient way. But good form is rare, because it requires focus, which most of us struggle with, so we forget to check our posture or alignment. For safe and effective exercise, give these your full attention. Think less about getting to the end of the exercise, and instead focus on the moment, bringing your awareness to each and every muscle movement. This is what it means to be mindful of form."
In yoga, people get sidetracked by "form" -  form is gradually accumulated by paying attention over a long period of time to one's own proprioceptive input, and interoceptive input. It doesn't really spring forth fully formed. It's important in yoga to build it oneself, not be externally focused, or let a teacher handle your body for you, or push you into "correct pose" or "proper posture" - if that happens, protest! If you layer in the feeling of improved "form" over time, it will instead become an emergent (inside-out) phenomenon, and not an artificially-imposed-from-without, possibly even nociceptive, externally-corrected constraint on your humanantigravitysuit. Which is, after all, the only place you have to exist. Never let anyone outside you push you around.
5. Recovery:
"Recovery is important between strenuous activity and between different exercises. It requires an awareness of your physical, emotional and mental wellbeing. In the pause between exercises, remain alert and focus on your breath and other sensations. Remember your breath is a barometer to your level of effort. Are you hunching your shoulders, limiting your body's capacity to take in more oxygen? Or even holding your breath? Both will create physical tension and slow your recovery. Good recovery is essential to remain injury-free."
Yoga has a wonderful "pose" called the "corpse pose" (a name that sounds a lot more attractive in its original language). It's my favorite. Basically, it's supine on the floor. On one's back. Flat. Arms and legs full out and relaxed. Still breathing. Deliberately. Fully. Fully inhaling, then exhaling. Not very frequently. It's incredibly relaxing to just lay there, and not do anything except breathe once in awhile, and feel your whole body flatten down onto the floor like the unconstrained water puddle it yearns to become some day, let it practice doing that, even as you're still alive in there and will be for a good long time to come.

Trigger point model deconstruction, models in general

Today I noticed a retweet from a (Spanish, by the look of things) twitterer,  @argoicoechea, who keeps a blog (Goicoechea arturo, his own name, surname first. Here is his bio). 

(Thank you, Chome browser, for making translation so darn simple.) 



What caught my eye about this tweet was that it was about trigger points. So I checked it out. Fibromyalgia, myofascial pain, tender points and trigger points: splitting or lumping?
Open access. I had not seen it yet, when I wrote Why I don't buy the idea that trigger points are in muscle, in July '11. (I don't retract anything I said in that blog post, just in case anyone is thinking I might.)

The paper is co-authored by a pair of researchers, one of whom represents the staunch mesodermalist assertion by the look of it (Bennett), and the other not so much (Goldenberg); it is written in debate-style, point-counterpoint format. 

ABSTRACT: Myofascial trigger points (MTPs) have long been a contentious issue in relation to fibromyalgia, and poorly defined pain complaints in general. Can MTPs be reproducibly identified? Do MTPs have valid objective findings, such as spontaneous electromyographic activity, muscle microdialysis evidence for an inflammatory milieu or visualization with newer ultrasound techniques? Is fibromyalgia a syndrome of multiple MTPs, or is focal muscle tenderness a manifestation of central sensitization? These issues are discussed with relevance to a recent paper reporting that manual palpation of active MTPs elicits the spontaneous pain experienced by fibromyalgia patients.

One of the papers cited by Goldenberg is by a few people I know online.
Lucas N, Macaskill P, Irwig L, Moran R, Bogduk N. Reliability of physical examination for diagnosis of myofascial trigger points: a systematic review of the literature. Clin J Pain.2009;25:80–89. doi: 10.1097/AJP.0b013e31817e13b6. [PubMed] [Cross Ref]

What is a "model"?
I think of a model as a thought bubble. The more variables it can account for, the bigger and shinier will be the bubble, the more opportunities it will provide more people (bigger 'surface area') to see through, to clarify their ideas of physical existence. 
Stephen Hawking, who just celebrated his 70th birthday in spite of having had ALS for decades, is quoted as saying,  “A model is a good model if first it interprets a wide range of observations in terms of a simple and elegant model, and second if the model makes definite predictions that can be tested, and possibly falsified, by observation.”    

So, here's the thing: a model that posits muscles as being bad guys and giving rise to "pain" is a poor model. Problems with the model include:
1. It was built on palpation! 
2. The palpators who push the current muscle (mesodermal derivative) model either deliberately ignored highly innervated custis/subcutis they were palpating through, and therefore didn't explain how they could subtract it as a freakishly unconstrainable confounding variable (bad on them) or else never thought to include it in the first place (still bad on them, but perhaps a bit more forgivable). 
3. Its perpetuators still refuse to consider that the nervous system itself is a probable confounding variable, or how to constrain it (probably because they can't (!) so they keep hoping no one notices. Hey! I notice!) 
4. As Goldenberg points out, interrater reliability is a problem. It stands to reason it would be; unless and until palpators from any school of thought figure out someday how to remove the blubber layer, with all its embedded cutaneous neural structure and unpredictable fractal nervous system qualities which derive from the nervous system's own strong opinions about protecting its organism in each and every moment from exteroceptive environmental threat, models built on palpation only are doomed to be consigned to that category known as belief systems or pseudoscience. The only other way to study sore spots via palpation, in an honest way, would be to include that layer.  
5. Goldenberg: "Just like fibrositis and fibositic nodules have become historical curiosities, MTPs will eventually be discounted as discrete pathologic abnormalities in the muscle." 

I see this image: a triggerpointer injector or investigator who insists trigger points are caused by muscle misbehaviour or pathology sits up on top of a silo, his "model", high and dry, eyes covered by blinkers and ears stuffed by fingers, while a big wet tsunami of neuroscience and biopsychosocial investigation of nociception and pain swells and surges around him. As long as he can artificially control the height of the silo upon which he is perched, by adding more "research" purporting his pet model, the wet won't touch him. But man oh man, that silo will rot away one of these days, and he'll fall in. 

Friday, January 06, 2012

Does this cab make my hippocampus look big?

Lots rattling by today.

1. First, from Deric Bownds Mindblog:


Structural changes in adult brains caused by acquiring knowledge
Excerpt: "We conclude that specific, enduring, structural brain changes in adult humans can be induced by biologically relevant behaviors engaging higher cognitive functions such as spatial memory, with significance for the “nature versus nurture” debate."

OK, so using cognition for spatial memorization will physically bulk up the hippocampus in London taxi drivers. Cool. 




2. Next, from Body in Mind blog:

First impressions do count! Especially if you’re stressed.
          File under, "You never get a second chance to make a first impression."
Kind of important if you're a human primate social groomer, with control only over the context you set for patients. This requires attention to details such as the sensory input your patient's brain will encounter, including noise levels, light, smell, cleanliness  color, temperature, and attention from you. 
It stands to reason that as their brain takes in a new setting, it will be "externally" cognizing. If their bringing you a pain problem to treat (most of them do), they are likely to have found themselves at odds with their own internal cognizing capacity in one way or another. 




3. Which leads me to (open access):

Echoes of the Brain within the Posterior Cingulate Cortex
ABSTRACT: There is considerable uncertainty about the function of the posterior cingulate cortex (PCC). The PCC is a major node within the default mode network (DMN) and has high metabolic activity and dense structural connectivity to widespread brain regions, which suggests it has a role as a cortical hub. The region appears to be involved in internally directed thought, for example, memory recollection. However, recent nonhuman primate work provides evidence for a more active role in the control of cognition, through signaling an environmental change and the need to alter behavior. For an organism to flexibly react to a changing environment, information processed in functionally distinct brain networks needs to be integrated by such a cortical hub. If the PCC is involved in this process, its brain activity should show a complex and dynamic pattern that partially reflects activity in other brain networks. Using fMRI in humans and a multivariate analysis, we demonstrate that the PCC shows this type of complex functional architecture, where echoes of multiple other brain networks are seen in separable yet overlapping subregions. For example, a predominantly ventral region shows strong functional connectivity to the rest of the DMN, whereas two subregions within the dorsal PCC show high connectivity to frontoparietal networks involved in cognitive control. PCC subregions showed distinct patterns of activity modulation during the performance of an attentionally demanding task, suggesting that parts of the dorsal PCC interact with frontoparietal networks to regulate the balance between internally and externally directed cognition.

If what we are about as human primate social groomers, trying to help patients learn to move better, or watching to see if they can move better as a result of our therapeutic interaction with them based on our physical contact with them, or both, it would likely help us to know a bit about how our patient's brain processes internal and external cognition. One already by default is an external distractor for their brain to process. One's goal is to teach them how to focus on themselves, go inside and focus on their own movement, interoception, proprioception, etc., and at the same time use the information you've given them, the ideas you've presented them, about pain, about how the brain descendingly modulates it. For that to happen successfully, as their groomer you have to become unintrusive and invisible so their brains don't have to worry about you anymore.


I am now going to go away, ingest, then digest this delicious-looking paper in a leisurely manner. I'll write any thoughts about it I may have.

Monday, January 02, 2012

Sunday, January 01, 2012

Happy New Year



It's a new dawn, it's a new day, it's a new life



I saw this posted today on Facebook by Alice Sanvito.

Fits me like a glove. Lots of biologic reference in the words, physiology suggested by the blobbishness of the images. Uplifting lyrics sung in a bluesy way. Still not much in the way of colour.

Getting there maybe. Not yet though. Just keep going.

Great song.

Saturday, December 31, 2011

"We're here, because we're here, because we're here, because we're here"

The title is a string of words that can be sung to the tune of Auld Lang Syne.

Last night I had a dream that I accidentally, serendipitously, learned how to fly. The details (setting, location, circumstances, others in the dream, etc.) are completely banal. After learning to fly, I got terribly excited, anything else that had been going on in the dream faded away, and I spent the whole rest of the dream practicing.

I learned to steer by pronating and supinating my hands and feet. I learned to do somersaults. Marvelously, I not only could make my own body weight disappear completely, but anything I picked up and flew around with became weightless as well, even something the size and weight of a human larger than myself.

I have no idea what any of it means - all I know is, it was a really cool dream. For a change.  Maybe it means my life-long grumbly mood/mild but constant depression could one day dissipate.

Thursday, December 29, 2011

Over the hump

I'm pleased to report the worst time of year (in my existential experience) is done, finished:

1. Winter solstice has come and gone.
2. Christmas, that annoying, overly-social, intrusive sensory event, is over.
It drives me nuts, every year - but this year the place I've been going to daily to work out played loud Christmas music, mostly Kelley Pickler, country music singer who was an American Idol contestant a few years ago. That, plus all the usual - TV ads selling stuff, news reports about retailers feeling anxious, sparkly glittered-up bling all over everything, light displays - all of it made me deeply empathize with autistic kids who don't deal well with over-stimulation. Uck. 
3. My birthday, which was yesterday, passed by uneventfully and non-socially, and is now over with! Yay!

Anyway, back to point 2. for a moment; sensory overload got so bad at that little gym that I decided to skip last week. Plus I indulged in Truffles, eggnog, and Bailey's. Oh, and an omelette with cheese, tomato, and buttered toast. And I ate some delicious dates. Plus other holiday food, like stuffing. And I did not exercise, at all, for a week. Up by a few pounds. Back at the elliptical  this week. My stamina has increased - up to an hour on that thing - probably had to do with being able to watch uninterrupted, Australia, with Nicole Kidman, Hugh Jackman, Brandon Walters. It's not just interesting, it's well done, and a lot longer than most Hollywood movies. So, it has kept me going all week. I've watched large chunks of it for three days, and there are still parts I've yet to see.

Speaking of movies and cognitive distraction, I saw this awhile ago, How muscle fatigue originates in the head. Rather than blame the mesoderm (muscles) for fatigue, researchers are starting to look elsewhere, and have noticed how the nervous system inhibits muscle at various levels. In the brain, interruption occurs when the thalamus and insular cortex decide they have had enough. I seem to be able to shut out the din my thalamus and insular cortex try to mount, by watching 'Australia'. At least for a little while. Then I will need another movie I've not seen before.

From yesterday, The Fat Trap: It seems a bit depressing, but before I started all this business 3 and a half years and 40 pounds ago, I knew it meant:
1. I could never eat (completely) unconsciously ever again as long as I lived
2. I'd have to move a lot more, learn to sweat, learn to get my heart rate up, learn to like it. Somehow.

I had a long plateau in there, a couple years where my weight went up by ten, down by ten, but never went completely out of control. It was always around this time of the year, this nadir time. So, I'm pretty sure I can reach old age in fairly good shape, plus all the exercise is not just for weight loss but is good for a bunch of other stuff that has to do with health, brain function, etc.etc. Nowadays, I'm on the other side of the year's nadir, and (even with my dive off the wagon for a week) my weight is still lower than it has been in 15 years. I take heart from that.


I'm pretty sure, that like pain, obesity is biopsychosocial. It's not strictly a fault in character, or strictly about genes, or hormones, or strictly about bad habits (see picture). A calorie is a nebulous thing depending on what kind of human organism ingests it, what sort of food it comes in, and why it is being consumed. Everything exists in a multiply-leveled context, including a conceptual entity known as a calorie.

This notion, Fat may put the Hypothalamus on the Fritz, needs more work I think. It suggests that ingesting fat "causes" inflammation in the neurons around the hypothalamus, but Harriet Hall says, inflammation isn't always a bad thing.  Gumming up Appetite to treat Obesity proposes that special hormone-laced gum should be helpful. But I doubt there will ever be any kind of easy answer.

If I were to pick a single brain region to target, to investigate, to spin a theory around, it would be the suprachiasmatic nucleus (SCN). In fact, I already did. It has to do with sleep, with light levels, circadian rhythms, depression, hypothalamus, all sorts of things that are regulatory. The pituitary, part of hypothalamus, has to do with thyroid, which has to do with a bunch of hormonal and metabolically important outputs. I moved myself physically back to where my own humanantigravitysuit, myself as a human organism, grew up. Environmentally, climactically, photonically, my brain feels better here. This is what it remembers from its youth. The long slow dawns and dusks, bright fiercely blue skies, brilliant reflective surfaces, deep blue shadow. Sensorially, and socially, the surroundings are kinda dull, but frankly, I don't much care about lack of sensory or social stimulation; I'm used to it again; furthermore, I like to be by myself anyway, except on the internet, which is where I live, mentally, most of the time, so it doesn't matter. (Plus, I lucked out joining a weight-loss outfit that happens to suit me to a tee, and happens to ALSO be the only one of its kind - in the whole of Canada so far - imagine, humble little old Weyburn, Sask. has a one-of-a-kind thing that suits me to a tee, and I just happen to live here where it is. Amazing happy co-ink-a-dink.)

But back to causes of things, no one thing causes obesity, and everything combined causes obesity. Actually, the pursuit of "cause" in science (pharmaceutical science at any rate) seems to be a bit endangered in and of itself, according to Jonah Lehrer.

So, what then is "obesity"? Well, I would ask, what is a relationship that an organism of any mammalian multi-cellular sort has with its whole bio-psycho-social environment? What is stress? What is pain? What is learned helplessness? What is failure to move one's physicality sufficiently? All these things are "caused" by everything simultaneously, often overlap by a lot, and all influence each other. Mostly, we are biologically active bundles of multitudes of proteins without distinct boundary (other than those we dream up then feel compelled to defend fiercely), with a big microbiota with a big microbiome (especially in the gut tube) that tends to run our lives more than we care to admit, probably... all the single-cell critters of which evolve, have lives, reproduce and die according to what they get (what we give them) - to eat. It seems likely that they might have evolved ways of trying to harness us, their big vehicles that lumber forth to get groceries, so that they might get what they need in order to keep going. Not that we are obliged to feed them endlessly.. just knowing that the mammalian multi-cellular organism is more an ecosystem than it is a discrete entity gives me hope that I can explore, map, cultivate and tame my own - in the end, it's all I've got.  I live on a little mountain-top in there with a pretty good view. At least, my "I"-illusion does. It's a welcome bit of conceptual structure; another bit is provided by the idea, that biochemically their lives are completely controlled, attracted to, or repelled by chemical gradients, described in pretty good detail in Into the Cool. This knowledge makes me feel powerful, or at least, enough of an independent, detachable agent to be able to manage my own small corner of the universe, my body, to my own liking.

There is a psychological aspect to all this that must be mentioned - eating consciously means tracking what's ingested, counting calories, including those sweated off, and attending daily to all of it. This could lead to either OCD, or anorexia, or both. Yet, those are cognitive-behavioural constellations one must approach in order to lose weight/become healthier. What I've learned is that you can learn how to dance with these two things, but you must always be in the lead, never the one who follows. It's kinda goes against dance training in general, for females, but I seriously recommend remaining in complete control of everything, including short breaks like the one I just took.

Now I must go and drown my microbiota yet again in a whole bunch of vegetable matter, which I know it doesn't like much, and which will likely kill off some more of it, making evolutionary space for new kinds that might actually like vegetables. (AHHHHGH! Hulk destroy bad microbiota!)

Sunday, December 25, 2011

And here we go again

... Another trip round the sun.

I suppose, if we have to mark time, watching axial tilt of our "ship", and changes in sun-shinage upon its surface, isn't such a bad way to mark it.

1. If you click on What Christmas Is All About, some money will go to Doctors Without Borders. Yeah, it's from last year. I like it.

2. Here's Neil deGrasse Tyson on how we're all stardust, so considering the universe should help us all feel expanded.



3. Goodbye to Lynn Margulis, microbiologist whose work on symbiosis helped move evolutionary theory forward, and mother of Dorion Sagan, son of Carl. Goodbye to Christopher Hitchens, who lived life the way he wrote, fast with a lot of mistakes according to many.

4. Have I left anything out? Oh yeah, tons. But it's all fine. It's all stardust. It will all recycle itself unendingly.

Friday, December 23, 2011

Consciousness and control



Fabulous video of Antonio Damasio discussing (in under 19 minutes!) "The quest to understand consciousness".

Whatever it is, without it we might as well be dead.

If we accept the idea that we need to have a conscious mind, a mind with a "self" in it, then that self illusion needs the illusion of efficacy. Which brings me to the next link, Born to choose: the origins and value of the need for control, the most interesting paper (review, pdf) I've seen today and maybe all year (free access).


"Belief in one’s ability to exert control over the environment and to produce desired results is essential for an individual’s wellbeing. It has repeatedly been argued that perception of control is not only desirable, but is also probably a psychological and biological necessity. In this article, we review the literature supporting this claim and present evidence of a biological basis for the need for control and for choice-that is, the means by which we exercise control over the environment. Converging evidence from animal research, clinical studies and neuroimaging suggests that the need for control is a biological imperative for survival, and a corticostriatal network is implicated as the neural substrate of this adaptive behavior."

The authors move through the psychosocial/behavioural evidence first, then the biological.
Therapy is all about restoring choice to patients, helping them overcome learned helplessness, no matter the level at which it was learned.

Tuesday, December 20, 2011

Longest darkest night of the year

I have this week and next almost all to myself. Such a treat. Life, on the whole, is getting better as time goes by, I'd say. For such a lot of years it got nothing but worse, and I used to simply ignore by what extent it was getting worse, and just carry on.  I speak of my own seasonal affective disorder.
This time round, things are upswung: I'm half way to the arbitrary weightloss goal I set back in September, when I started exercising, and I can actually feel some ab strength. So that's nice. I almost have my new place to work at set up, so that's nice too. The new year will freshen the page.

Most stuff just floats by in this flood called life and the way it interacts with my soggy winter brain, but once in awhile something sinks in and leaves an impression;
Lately on FaceBook a dustup occurred on my page, to do with craniosacral treatment. The pattern of kuffuffle that ensues with alt-meds has become predictable. I take no offense anymore, just wait for it to blow past and be over. Each time this happens more and more people seem to come out of the woodwork and identify themselves as anti-woo, so that's good. 



The first link, the one that upset a few folk, was to a post by Mark Crislip at ScienceBased Medicine, about craniosacral therapy: Alas poor Craniosacral. A SCAM of infinite jest, of most excellent fancy, was pointed and funny and skewered CST completely and deserved more publicity. I posted the first FB link without comment, and moved on. But before long, there were 83 comments.


Deciding to continue with the topic I posted a second link to a report from a few years ago, about an infant who had died while undergoing "craniosacral" treatment. That one got 107 comments. 


I put up a third link to a very fair objective overview of it all written by a massage therapist, 

A case of moral distress: defending counterfactual anatomical claims in CST

 It's still perking right along. 
........


None of this is novel, so it doesn't interest me as much as the perspective offered by Mark Changizi, in his recent blogpost, "How not to get Absorbed in Someone Else's Abdomen". 
"Synposis: Anglerfish are metaphors for how creative communities can eat your brain and kill your creativity."  


That's what happens to us, as humans. Exactly. You could even say the world humans have created has become one big abdomen with many entry points into which we dive willingly for safety and so we don't have to think anymore, and can let our brains resorb. 
"Communities of people have bulls-eyes on them that are irresistible to us humans." 
Read it! It's a great blogpost. Changizi compares the behaviour of the anglerfish (the male one, anyway) to the way humans (neotenous apes that we are) need to have approval and feedback and support and eyes on us for every little thing we do in the world. Our need for external approval overwhelms our need to stay connected to our own cognitive linkages; all too easily are we severed from them, led into believing whatever somebody says is true, whatever nonsense they might be selling. We default straight to trust. We believe purveyors of nonsense, because they said it was science-based and why wouldn't we accept what they say? They're the teachers, right? 
........


And I saw this: "Doctors disagnose diseases as if recognizing objects", by Mo Costandi. It stuck in my head for some reason. I figured out, oh, it stayed in my head because they (doctors) are themselves lost in the abdomen of their own profession. Ah. No wonder we're in such trouble, us PTs who try to balance all the biomedical whatnot with our own whatnot. Because, what about pain? It has to be diagnosed, but it isn't "objective". It's not an "object". It's biopsychosocial. It's not physical. Pain science is the keen edge of the knife separating us from that abdomen we thought was "real" and "safe" but instead is a big (biomedical) fish net capturing health care dollars. We need to be discerning. We need to know what's useful for us, compared to what's useful for them. Not get mixed up about our role. Swim outside that big medical belly our profession seems to like to mix it up with. But never ever get sucked into/attracted toward other nice-looking abdomens. 


That default move (diving into a pre-existing conceptual abdomen) is not the best default move, but it's the quickest, and it's understandable: Why? Because we have huge, probably mostly unmanageable brains. Our executive function (dorsolateral prefrontal cortex) isn't even fully myelinated until we're close to thirty years old, then it takes awhile after that before we learn how to use it properly. Seth Grant says, 
"it has been said the number of synapses in the human brain is about a million billion, but something we’ve discovered about the molecular composition of the synapses, is that they have over 1000 different proteins within this, and we have done sort of a back-of-the-envelope calculation about the computational power of the human brain, based on what we know about the molecular circuits and these neuronal circuits, and we’ve come up with this very simple estimate: and it is that one human brain is more powerful than all computers on the internet put together, times one hundred."
That's a lot to keep any sort of handle on, seems to me. Seems to me, insecure humans diving for the nearest collective conceptual abdomen is like iron filings diving toward magnets - automatic, pretty much irresistible. Not to excuse those who lazily persist, who don't learn to resist the compulsion.


.....

Finally, on a seasonal note, I read and very much liked Less Wrong's solstice celebration blogpost: Ritual Report: NYC Less Wrong Solstice Celebration. 


It sort of puts the whole thing into a bit more perspective. The whole notion of sharing stories and candles going out until only one candle was lit, enough light to read the last story, dredging up enough collective courage to face what could be a long hard winter. 

"We honor those people, those first astronomers, and all the laborers and scientists and revolutionaries who have come since, for creating the world we have today.
And then we look to our future. Tiny stars in the distant sky, unimaginably far away, surrounded by black seas of infinity.
We will stare into that Abyss, and the Abyss will stare back at us. But we will go crazy-meta and challenge the Abyss to a staring contest and win the hell at it, because we’re aspiring rationalists and good rationalists win."

.....
And, to tie all this in once again to craniosacral therapy, I leave you with this video, which reminds us all of how vertebrates are often extraordinarily kind to one another and anything with sensitive paws can do cranial effectively - it isn't necessary to imagine a lot of complicated implausible mechanisms, when you care enough to want to do something helpful with another nervous system you can sense is not very happy with itself. 




Have a nice smooth holiday, an uneventful exit from this year to the next; may your next trip round the sun also be uneventful or maybe even growthful. 

Saturday, December 17, 2011

"Contextual Architect" - Cory Blickenstaff

Recently Cory wrote a letter to the editor of the Journal of Manual and Manipulative Therapy, which I've decided to quote in full (and hope I'm not breaching any copyright by doing so):


"Therapist as ‘contextual architect’ 
I would like to thank Bialosky et al. for their excellent article clarifying and discussing how and why to maximize placebo in manual therapy(1) practice. I would like to consider here the implications that placebo, conditioning, and expectation have on our roles and responsibilities as manual therapists. 
As pain is the primary complaint of many patients seen by the manual therapist, the potentially ubiquitous involvement of placebo in the ways we might approach these problems makes understanding such issues of vital importance. 
The authors operationally define placebo as the context of interactions between patient, therapist, environment, and intervention. A useful way to conceptualize these modes of interaction in the therapeutic encounter would be to consider three conceptual spaces: the subjective spaces of each the patient and the therapist, and the third shared ‘inter-subjective’ space (consisting of the environment and the intervention in the model of Bialosky et al.). Let’s examine how each space contributes to the ‘context of interaction’. 
The subjective space is private. Quintner et al. argue that the lived experience of pain is an example of an aporia, (2) a space to which an observer is denied access.(3) We lack a usable language to have access to the subjective experience of another (4) (such as the pain experience) and must therefore rely on indirect interpretation as exemplified by tools such as the visual analog scale, self-report disability scales and on our own interpretations of the interaction. All of these must be drawn from the shared inter-subjective space. 
The shared inter-subjective space represents the place where we can and do impact the other person through shared environments (including the intervention). When we interact with another, we become both the observed and the observer,(2) as we impact their subjective space and vice versa. 
Relevant to the inter-subjective space in therapy is the idea of soft paternalism that states that we cannot help but influence those with whom we interact. In other words, you can ignore the impact you have on context, but it will not ignore you, nor will it ignore your patient. This is a point the authors successfully drive home in their review, and Jacobs and Silvernail defended with the introduction of the ‘interactor’ approach in a previous response letter.(5) We should therefore strive to affect the interaction in specific and predictable ways, aiming for certain outcomes while respecting the rights of the individual involved.(6) As the authors point out, the evidence of impact of care gives us some insight into predictable outcomes of various forms of interaction. As we are attempting to build a specific context of interaction in the inter-subjective space to bring about predictable outcomes, we as manual therapists reside in the role of contextual architect. 
Our responsibility as contextual architects is to be purposeful in our influence in a responsible manner as prescribed in our code of ethics,(7) using predictable methods (when available) and plausible explanations consistent with best evidence with the patient’s individual goals and best interest as the guide.
Cory Blickenstaff PT, MS, OCS Forward Motion Physical Therapy Vancouver, WA, USA
References 
1 Bialosky JE, Bishop MD, George SZ, Robinson ME. Placebo response to manual therapy: something out of nothing? J Man Manip Ther 2011;19:11–19.
2 Quintner JL, Cohen ML, Buchanan D, Katz JD, Williamson OD. Pain medicine and its models: helping or hindering? Pain Med 2008;9:824–34.
3 Williamson OK, Buchanan DA, Quintner JL, Cohen ML. Pain beyond monism and dualism. Pain 2005;116:169–70. 
4 Scannell K. Writing for our lives: physician narratives and medical practice. Ann Intern Med 2002;137:779–81. 
5 Jacobs DF, Silvernail JL. Therapist as operator or interactor? Moving beyond the technique. J Man Manip Ther 2011;19(2): 120–21. 
6 Thaler RH, Sunstein CR. Libertarian paternalism. Am Econ Rev 2003;93:175–9. 
7 American Physical Therapy Association. Code of Ethics [docu- ment on the Internet]. Alexandria, VA: American Physical Therapy Association. Available from: http://www.apta.org/ uploadedFiles/APTAorg/About_Us/Policies/HOD/Ethics/Code ofEthics.pdf#search5%22Code%20of%20Ethics%22."
I made a picture of this awhile ago, that I call the 'therapeutic domain'. It's a not-yet-completely-satisfactory imaging of the interactor model of physical/manual therapy, taking into account the reciprocity of sensing that goes on between therapist and patient, which hopefully helps the brain of the patient resolve its pain production. 

I really like the term "contextual architect" - it provides room for creativity, and challenges all the other conceptualizations of manual therapy in existence that operate in "guilds" - i.e., here's the way it's done, do it this way, with these bricks, or you can't belong in this guild (how medieval is that?)

Way to go Cory - way to carve out more conceptual space for all those of us who are permanently dissatisfied with the current, inherited, mesodermalist climate that permeates most of manual therapy. Way to go, Journal of Manual and Manipulative Therapy, for holding open a door to new avenues of thought. 

JMMT is available online, but not accessible by me. Cory's letter appears in Vol 19, No 4, 2011.