Tag Archives: pain

Dreamland: bad organic chemistry edition

I am in the middle of a post on Dreamland (Sam Quinones) and how it is so wrong, but honestly I don’t think I can wait that long so here’s an easily encapsulated teaser.

On page 39 Quinones says “Most drugs are easily reduced to water-soluble glucose…Alone in nature, the morphine molecule rebelled.”  I am reasonably certain that is horseshit.  Glucose contains three kinds of atoms- carbon, oxygen, and hydrogen.  The big three of organic chemicals.  Your body is incapable of atomic fusion, so the atoms it starts with are the atoms it ends up with, it can only rearrange them into different molecules.  Morphine is carbon, oxygen, hydrogen, and nitrogen, and that nitrogen has to go somewhere, so I guess technically you can’t reform it into just sugar.  But lots of other medications have non-big-3 atoms too (although, full disclosure, when I spot checked there was a lot less variety than I expected).

This valorization of morphine as the indigestible molecule is equally bizarre.  Morphine has a half-life of 2-3 hours (meaning that if you have N morphine in your body to start with, 2-3 hours later you will have N/2).  In fat that’s one of the things that makes it so addictive- you get a large spike, tightly tying it with the act of ingestion, and then it goes away quickly, without giving your body time to adjust.  Persistence is the opposite of morphine’s problem.

This is so unbelievably wrong I would normally assume the author meant something entirely different and I was misreading.  I’d love to check this, but the book cites no sources, and the online bibliography doesn’t discuss this particular factoid.  I am also angry at the book for being terrible in general, so it gets no charity here.

The Compassion Pain Scale

I never did do much with the kitten pain scale, because the pain meds’ effects were so striking there was no need for hour by hour monitoring.  But I’ve found another good marker.

When I first started at crisis chat I really really loved it, and would frequently stay hours past my scheduled shift.  I often left feeling energized*.  At some point that changed.  I put it down to a loss of novelty, or maybe nostalgia making me remember it as more fun than it was.  I kept going because it wasn’t about me having fun, it was about me helping people, but I was more conservative about the latest time I would start a new chat.

Then I got those really awesome pain meds in January, and suddenly I was staying late again.  But at some point it disappeared again.

One of the nice things about the meds is that they have a long lasting effecting.  They push the pain-tension cycle back, so I’m in less pain for days or even weeks after they wear off.  One of the bad things about one of them is that I hate being touched the next day.  That’s suboptimum on its own, but it scares me to think of what else it’s doing that I’m not noticing, so I try to go as long as possible without taking it.  I’m also very good at pushing away conscious knowledge of pain, even though it still effects me.  So I ended up going really way too long without taking the topical pain medication.

Finally I took it again, and what do you know, I stayed more than two hours past the end of my next chat shift.

It doesn’t surprise me that I’m better at chatting when I’m in less pain, but I am surprised by the way I’m better.  Ending chats is a tricky business.  You don’t want people to feel shoved out the door, but a good chunk of our target audience is having anxious ruminations.  The last two times I’ve been much better about recognizing when we’ve reached the end of the productive portion of the chat and wrapping it up.  A few people even seemed to take the nudge out as permission to relax.

*although not always.  Most days I had to call a child abuse report in were bad days

**Shift end times are a little fuzzy because of course you can’t leave in the middle of a chat.  If it’s 5 minutes before your shift ends, of course you don’t take a new chat unless you’re prepared to stay late.  But if it’s 30-45 minutes?  You’ll probably be done only a little after your stated end, but you never know which call is going to be a two hour active rescue.

Xylitol for sinusitis

I’m taking on sinus inflammation because it’s a major contributor to my motion sickness, which is a major contributor to making commuting suck, and commuting is one of very few things that can actually depress your hedonic set point (psychologist talk for “make you miserable”).  My doctor has suggested xylitol nasal spray, which she claims inhibits irritation in the sinus cavities.  Quick googleing reveals it’s also considered useful for bacterial plagues on the teeth and in the arteries.  Let’s dig in.

Xylitol’s main claim to fame is as a calorie-less sweetener in humans. The claim is that it kills (many but not all strains of) bacteria via the same mechanism:  it can’t be converted into energy, so the bacteria starve to death.  This has to be to be missing a step.  Bacteria are surrounded by billions of molecules they can’t digest all the time, and they survive that.  If xylitol is to have an affect it must not only be indigestible, but inhibit digestion of actual sugar.  Off the top of my head there’s two ways that could happen.  In the human body, sugar is moved around by the blood.  If xylitol takes a sucrose molecule’s ticket to a particular area, there will be less sugar there for bacteria to eat.  The downside of this is that you might starve out your own cells.  Another option is that bacteria cells themselves become confused by xylitol.  The ideal would be if xylitol fit into a sugar receptor but couldn’t be taken into the cell, so the receptor was blocked indefinitely.  Or if it was taken in it could trigger a “yup, we got a sugar” reaction that caused the cell to take in sugar later, but I’m not sure why a bacteria would ever turn down calories.

I found a lot of studies on xylitol and dental use.  Most of what I learned is that dental abstracts are more like teasers than summaries, not cluttering up the space with numbers or sometimes even conclusions.  Overall there seems to be a mild consensus for xylitol mildly inhibiting cavities, although it’s certainly not a substitute for fluoride.  Also I totally should have been chewing xylitol while I was recovering from surgery, since is almost certainly disrupts oral plaques, although I worry about what it would do to the intestinal biome.

What about sinuses?  I found a lot of very small studies, but 5 studies of size n are not equivalent to one study of size 5n.  You don’t know how many more studies of size n were done but not published.

This study and this one found decreases in medical severity (as measured by the SNOT-20 score.  Yes that’s it’s real name), but not self-reported pain (as measured by the less well named VAS score).  This study in rabbits was well controlled (if small) and found significant decreases in bacteria.

rabbit
Rabbits self-reported pain scores were ambiguous

This study found that a nasal decongestant spray worked better than xylitol or saline spray, which worked about equally as well.  Nontheless it’s conclusion was that [name brand of xylitol spray] was an effective treatment for nasal congestion.  It also spelled spray with an ‘e’ .  Twice.

One interpretation of these results is xylitol helps impedes infection but irritates the sinuses such that there’s no change in pain levels.  Another is that people are really good at suppressing conscious knowledge of pain.  My experience has been I’m really good at suppressing moment-to-moment awareness of pain but I do notice when asked (which is how I went weeks without treating my dental neuralgia, and then suddenly noticed I was at 8 on the pain scale), and that the pain has a great deal of effect on my behavior and happiness whether I acknowledge it or not.   And if I keep using xylitol I need to change my brand to one that, when it buys positive press in a supposedly objective forum, spells its own name correctly.

Pain, ADHD, and happiness

I jokingly referred to pain-induced ADD on Monday, but I’m becoming more and more convinced that is actually what was happening.  After prior surgeries I was too exhausted to notice anything, but this time I was energetic enough to experience the pain.  I mean, unless I tried to go outside or something.  That led to a really entertaining systems crash in the supermarket.  But if I stayed inside I was able to do things like get food and put away dishes without strain.  Contrast with when my pain meds sabotaged my cortisol production.  Intellectually I was there and able to do things like read and blog, but physically it was a struggle to make myself a smoothie.

After surgery I could not read or write or even enjoy a movie.  It was more than pain making everything 70% less fun, it was that everything was annoying and frustrating and no fun at all.  I couldn’t enter a state of flow or concentration or even relaxing for any length of time.  Except when I played video games or the piano.  Neither were fun, exactly, and I was still in pain, but they were at least distracting and rewarding.  Looking back, this explains a lot of my behavior when I was in constant pain last year, it just took being out of pain and then very sharply in a lot of pain to make the pattern obvious.

At first I thought this was  Harrison Bergeron type thing, where pain was sending out interrupts too often for me to get into a groove on anything.  But then I read this blog post (blogs were just about in my power) by Sara Constantin on dopamine, explaining Peter Redgrave’s hypothesis that the spike (phasic increase) of dopamine is not itself a reward (which is how pop journalism usually describes it) but a timestamp that lets you know what actions should get credit for the actual reward chemicals you are about to receive.  That would explain why humans and animals with broken dopamine systems do feel pleasure when eating but will nonetheless starve to death unless you put the food directly in their mouth.

Many of the drugs used to treat ADHD inhibit dopamine reuptake, which raises your tonic (baseline) dopamine levels.  Constantin hypothesizes that if the baseline is too low than stimuli that should be ignored suddenly are interpreted as important, leading to a lot of SQUIRREL.

[ I was going to make this a gif but putting unpausable moving pictures in a post on ADHD just seemed cruel]

If this is correct, it offers an explanation for why ADHDers are so drawn to things like videogames and sex:  the time gap between doing the correct thing and getting the chemical reward is so short they can still determine causality, even against the a background of SQUIRRELs.  This needn’t be purely about hedonism- if it was, something consistently pleasant would work.  I think it’s about having an internal locus of control and self-efficancy.  Humans are happiest they feel like they have the power to change their own circumstances and have an impact on the world.  It’s hard to feel those things if your attention is constantly being torn away from what you choose and you can’t (on a neural level) determine what made you feel the emotion you are currently feeling.  This is one reason the toll of ADHD shouldn’t be measured in lost productivity alone; even people with very successful coping mechanisms are being denied that internal locus of control, and that’s miserable.

Here’s my contribution: my description of being in pain sounds a lot like other people’s description of ADHD, right down to video games being rewarding without strictly being fun.  And as it turns out the basal ganglion, the area Redgrave believes is using dopamine to timestamp causes so they can be matched with effects, also releases dopamine in response to pain.  It seems entirely possible to me that high baseline levels of dopamine could diminish the effect of a spike.  Instead of everything being timestamped “good job”, nothing is, with similar results

But let’s make it even more interesting.  Several anti-depressants are also useful in treating chronic pain, and NSAIDS (usually mild pain killers) treat depression.  I had previously put this down to “pain is depressing”, “depression appears to be connected to inflammation in ways we don’t understand” and plain old “brains are squishy and they don’t make sense”, but if there was a causal link?  The symptoms of depression include fatigue, feelings of helplessness and lost of interest or enjoyment of previously liked activities, which sure sounds related.  Quick googling found a very tiny study showing a connection between low dopamine and suicide, and this fascinating study suggesting that inflammation reduced the basal ganglia’s production of dopamine, which would tie all of this up in a very pretty bow.  Something causes pain and/or inflammation (the two often go together), which long term causes inflammation in the basal ganglia, which causes depression and reduces your body’s natural analgesics.

Look body, if you were worried about us getting high off of pain, maybe you could have releases fewer happy chemicals in response to pain, instead of making it just as fun but also cause depression some time later.

This would also explain why ADHD medicines are promising in treating depression (source, source, and a large showing among my friends), and why ADHD and depression so often go together.*

I cannot stress enough how unqualified I am to make this hypothesis.  Lots of people know lots more on all of these things than me.  But it comes together to be an extremely plausible explanation for both the literature I’ve read and my personal experiences.

*There’s a lot of evidence that depressed parents correlate with ADHD kids, but it’s probably environmental.

Humans are complicated, children are even more complicated

[Had more dental surgery this week and am currently suffering from pain-induced ADD.  Expect less research and more wild speculation]

Consider pre-emptive testing for psychiatric or developmental issues in children.  If you’re too aggressive, you end up misdiagnosing a lot of perfectly normal deviations from the exact median as development issues in need of treatment.  Development is complicated, different systems come on line at different rates and in different orders in different kids, and they should be allowed to do that without being corralled into fitting a predetermined schedule .

But if you’re not aggressive enough, the kids develop coping mechanisms that hide the disability, making it harder to diagnose and treat.  Sometimes people treat this as solving the problem (especially for conditions that are often conflated with character flaws, like ADHD or some forms of depression), but they are wrong.  At best lack of treatment holds people back from their true potential, at worst it twists up their internal structure in ways that break at the worst possible time (usually grad school).  It’s a big problem with twice exceptional children, who have both brain-based deficiencies and a lot of raw intelligence, and I suspect for people with atypical presentations of their disabilities.  E.g. girls with ADHD or autism spectrum issues, boys with depression* or trauma from sexual abuse.**

Even perfectly accurate testing won’t fix this, because developmental asynchronies do not necessarily indicate a future problem, and treating them can prevent the issue from fixing itself.  The real issue is distinguishing natural, healthy leveling out from the development of costly compensation mechanisms, and we don’t know how to do that.

*Assuming the comomn adult male pattern of depression being expressed as anger holds true for boys as well.

**I think, couldn’t actually find data on this.

The Kitten Pain Scale

I very briefly flirted with Quantified Self and then jumped off the bandwagon because it was making my personal signal:noise ratio worse.  But my neuroendodontist* has given me several drugs, and he wants to know how they work.  Allow me to give you a brief list of things that make measuring this difficult

  • Treatments are all on varying schedules- some daily, some daily with a build up in blood stream leading to cumulative effects, some as needed to treat acute pain, some on my own schedule but hopefully having longer running effects.  Some are topical and some are systemic.
  • I have several home treatments like tea and castor oil.  I’m not going to not take them in order to get more accurate assessments of the drugs, both because ow and because pain begets pain.
  • Taking treatments as needed + regression to the mean = overestimate of efficacy.
  • Pain is affected by a lot of non drug things: sleep, stress, temperature, how ambitious I got with food, amount of talking, number of times cat stepped on my face in the night, etc.
  • We are hoping some of these drugs will work by disrupting negative feedback loops (e.g. pain -> muscle tension -> pain), which means the effect could last days past when I take in.  In the particular case of doxepin it might have semi-permanent effects.
  • Or I could develop a tolerance to a drug and my response to a particular drug will attenuate.  That is in fact one reason I was given so many choices as to medication: to let me rotate them.
  • We have no idea how these drugs will interact with each other in me.  We barely have an idea how the interact in people in general.
  • If I believe something will help my pain will lessen as soon as I take it, long before it could actually be effective.  Not because I’m irrational, but because my brain reinforces the self-care with endorphins, which lessen pain.
  • At the same time, having more pain than I expected to feels worse than the exact same pain level if it was anticipated.
  • Side effects: also a thing.

“I think I feel better when I take this one” was not going to cut it.

Then there was the question of how to measure pain.  Ignoring the inherent subjectivity of pain, neuralgia is a weird beast.  I already hate the 1-10 pain scale because pain has threshold effects and is exponential.  I could create a single pain number at the end of the day, but my pain is not constant: it spikes and recedes, sometimes for reasons, sometimes not.  What I would ideally like to track is area under the curve of pain**, but that requires polling, which would create horrible observer effects.  If I ask myself if I’m in pain every 15 minutes, I will increase my total pain level.  I could poll less often, but the spikes are random and short enough that this was not going to be accurate enough to evaluate the treatments.  I could count pain spikes, but that ignores duration.  Determining duration requires polling, so we’re back where we started.  I could deliberately poke a sore spot and see how bad the resulting pain is, but

  1. Ow
  2. A treatment that doesn’t affect sensitivity but does keep me from spontaneously feeling pain because the nerve is bored is a success.  If we wanted me to be numb we would do that.

It’s just really hard to measure something when your goal is for it to be unnoticeable, and measuring it creates it.

So I came at it from the other side.  What happens when pain is unnoticeable?  I enjoy life more and I get more things done.  Could I measure that?  Probably.  They have the bonus of being what I actually care about- if something left me technically in pain but it no longer affected my ability to enjoy or accomplish things, that would be a huge success.  If something took away the pain but left me miserable or asleep, it is not solving my actual problem.**

So one metric is “how much I get done in a day”.  Initially this will be the first number between 1 and 10 that I think of when I ask the question at the end of the day, but I’m hoping to develop a more rigorous metric later.  You’d think enjoyment of life couldn’t ever be rigorously measured, since it’s so heavily influenced by what is available to me in a given day, but I say that brave men can make it so.  And so I introduce to you: the kitten pain scale.  Kitten videos vary a little in quality, but I think my enjoyment of any single video reflects my internal state more than it does the video. Three times a day (shortly after waking up, shortly before screen bed time, and sometime mid-day that can vary with my schedule but must be selected ahead of time to avoid biasing the data), I will watch a cute kittens video and record how much I enjoy it.  The less pain I am in the more I should enjoy the video.  This will give me a (relatively) standardized measure of pain without risking inducing it.

This is still not what you would call a rigorous study.  An individual choosing what to take among known options never will be.  But I seriously think the kitten pain scale could be a contender to replace the stupid frowny faces.  My first draft is available here.  Right now it’s set to measure over the course of a day, because that’s the scale I expect from these meds, but you can add bonus measurements at set times after taking meds if you like.

Possible additions: cups of tea drunk in day.  Right now that seems like too much work to measure, but when tea is available it’s a pretty good indicator of how much pain I’m in.

*I am still angry that I know what that is, much refer to one using possessive case.  But given that, I am extremely grateful I live within biking distance of a world class research facility in the discipline.  Even if the physical facility could be a case study in how economic insulation leads to bad user experience.

**This is why none of my treatment options are opioids.  Strong ones technically reduce pain, but they also leave me miserable.  The fact that some people take them for fun is all the proof of human variability I could ever need.

Adventures in Dentistry and Neurology

I forget if I mentioned it, but I had nerve damage from the first dental surgery, way back in June.  Everything else healed up more or less all right, but that one kept hurting.  Actually it felt like two damages- one that was healing, albeit slowly, and one that was staying static or getting worse.  The prospect of living with that pain for the rest of my life was really daunting.  Medical marijuana, which had been so helpful at first, was having more side effects with fewer desirable effects every day.  It eventually became clear my surgeon had no idea what was going on or how to fix it so I went to a neuroendodontist, a subspeciality I really wish I wasn’t already familiar with.

toenailectomy looks awful but feels like nothing at all.  A neuroendodontal exam is the exact opposite.  It looks like some guy very gingerly touching around your mouth, but he is not only deliberately provoking pain, he needs you to pay attention to the pain and report on in it excruciating detail, while you remind yourself that inaccurate reporting leads to inaccurate diagnoses.

For all that pain, I actually got very good news.  Even though it feels like I have two distinct damages, it’s actually only one, and it is healing.  Nothing is guaranteed in neurology but existing data is consistent with this eventually healing itself.  And in the meantime, he gave me new and different medicines.  We’ll see what the side effects are, but at the very least I have options to rotate through.

Adventures in Podiatry and Neurology

WARNING: THIS ONE IS GRAPHIC EVEN BY MY STANDARDS.  NEEDLES, PAIN, AND TOENAILS.

Recently I learned toenails aren’t supposed to be under the skin of your foot and hurt constantly; this is an ingrown toenail and it’s a solvable problem.  By “recently” I mean a year and a half ago, but a little pain when I flexed my toes in a shoe did not seem as important as the pain in my mouth or my inability to digest food, so I only got around to seeing a podiatrist now.  If you develop an ingrown toenail there are home treatments to coax it better, but if you’ve always had it the cure is a little more drastic: they cut off the bit of the nail that has grown under the skin and cauterize the nail bed so it never grows back. If you are curious, here’s a video of the actual medical procedure:

The worst part is the lidocaine injection. There’s a topical anesthetic, but they root the extremely thin nail around under your skin in order to find the nerves and inject directly over them. The podiatrist will describe it as slightly painful, but they are lying, and it will make you doubt them when they promise the rest of the procedure is painless. That part turned out to be true: with enough lidocaine you genuinely can’t feel them slip the scissors/pliers under the nail bed, or the burny stuff*, unless you are a freak who processes -cain very quickly, in which case they will give you more and it will stop hurting.  But the anesthetic injection was pretty brutal.

That is not actually the interesting part. In between the lidocaine and the scissors/pliers, they test your numbness with what looked like a large blunt toothpick. My podiatrist, which more flourish then was strictly necessary, brought it down from a great height onto my toe.

I screamed.

Then I realized it didn’t hurt at all. My brain had combined the memory of the painful needles and the visual information about incoming sensation and preemptively sent a scream response before it noticed I couldn’t feel anything. I never had quite that strong a reaction again, but there was an extremely weird dissonance as I watched something I knew should hurt, yet got only vague reports of pressure from the area.

This works in reverse too.  Phantom limb syndrome is a condition in which people missing a limb (even one they never had) experience excruciating pain where their brain thinks that limb should be.  One of the only effective treatments is mirror therapy, where a mirror is used to simulate the appearance of the missing limb, and somehow the brain goes “oh, I guess it’s fine.”  This clip from House is not quite as accurate as the matrixectomy one (mirror therapy rarely involves kidnapping), but the science is sound.

The lesson here is that even something that feels incredibly simple and real, like pain, is in fact an artifact of post-processing on several different inputs.

*Dr. Internet says phenol but I could have sworn it started with an M. In my defense, he gave me the proper name after the needles bit and I was fuzzy.

Cannibidiol for pain: a partial retraction

Earlier I described CBD as having absolutely no effect on cognition.  This turns out to be wrong.  I’ve subsequently found that CBD does impair cognition somewhat relative to optimal, it just does so less than pain.  And at least for me, it doesn’t wear off quickly: if I take it at night I’m in less pain the next day, but I also have trouble focusing for long periods and doing truly complex work.  It feels like I can’t get far enough away from problems to see the whole of a thing.  If my choices are “in pain and dumb” or “not in pain and dumb”, I choose door 2, but this does make me more forgiving of NSAIDs.

In other news, they finally took my bone spur out and wow, I’m in a lot less pain.