Drifting on the (zicono)tide

I was going to launch into a full-fledged discussion about one of the newer synthetic drugs, ziconotide (also called Prialt), but I realised I haven’t really explained about pain. Specially chronic pain. So I’m going to go into yabber mode, and explain what (very little) I know about pain, and why ziconotide is important.

Unfortunately, that means a long lecture. Probably boring too. Incredibly boring. So to minimise the possibility of your gut trying to strangle your brain to stop the insanity, I’ll try and break it down as much as possible into small, easily digested lumps of technical babble. You can then choose to chuck it back up, or learn summink. It’s entirely up to you.

Writing about this also helps me get things straight in my own mind – to make sure I really do understand about pain, and (more importantly) when pain goes wrong. So let’s get started!

Oh, the Pain!

We all kinda know nowadays that pain is transmitted by nerves to the brain, where some very fast thinking is done, and the brain then sends signals back down the nerves to take our hand off the burning kettle (or whatever it is that we’ve accidentally touched or fallen on).

That’s actually quite amazing, when you think about it. Forty or fifty years ago, people like you and I didn’t know even that much about pain (though we all become experts at trying to avoid it). I suppose unless you’re especially clumsy (like me), you don’t really experience pain often enough to want to know what the hell makes it work. And I agree knowing about it doesn’t help us avoid it all that much, and it sure as shit doesn’t make the pain less! Still.

So this kind of pain/response is called “acute pain”. It’s a stimulation of a particular nerve receptor (heat or pressure) that causes (hopefully) an instant reaction to stop the pain from continuing. As far as it goes, that’s a great adaptation of our bodies to stop bad things from getting worse.

In the late 17th and early 18th centuries, it was believed that only Man could feel pain, and that animals somehow were mechanically motivated to emulate the display of pain, but they didn’t actually “feel” pain the way we do. So some scientists performed all sorts of experiments on living animals. I won’t go into these experiments, except to say if you don’t think nailing a puppy’s paws to a wooden board and then disembowelling it and skinning it to see what made it scream in agony was a good idea, I’m with you. That neither benefited the cause of science, nor did it prove anything apart from a shocking cruelty reflected in the rest of that backward society.

On that subject : this view of “Man” as the “ultimate being” on Earth, was just one more example of what religious thinking does to normally sane and rational people. I can’t think of any good reason to conduct such an experiment, on any animal, let alone to try and prove that your disgusting religious idiocy was somehow real or true. But that’s food for another post altogether…

What about when things go wrong?

So acute pain and it’s reaction helps us avoid or minimise damage to ourselves. But there are two really interesting instances of what can go wrong with such a mechanism. One is caused by bacteria, the other – well, we just don’t know what causes that. But I’m trying like hell to find out!

When we feel no pain : Hansen’s Disease.

How many times have you wished that you couldn’t feel physical pain? I’ve lost count, personally, but it turns out that not feeling pain is far, far worse than putting up with it!

Perhaps the most extreme form of failure in the pain response system is caused by two types of tiny little bacteria, Mycobacterium leprae and Mycobacterium lepromatosis. You can kinda tell from the names what I’m going to talk about.

Now, the bacteria doesn’t directly cause the horrific and life-changing features of Hansen’s Disease (otherwise known, wrongly, as leprosy). In fact, the bacteria seem to cause nothing more than the absence of pain, which you’d think would be a pretty good deal! I won’t go into detail about how the bacteria actually do what they do, you can find excellent articles about the mechanisms for Hansen’s Disease on Wikipedia.

The problem with this disease is that it stops people from feeling pain, particularly in the extremities, like your feet and hands. Now, if all that’s happened is that you’ve barked your shin on a coffee table without breaking the skin, there’s no major cause for concern.

But if you have Hansen’s Disease and you’ve accidentally stood on a rusty nail, or cut yourself, you just won’t feel anything! Then chances are good that you’re going to not treat the wound, and that’s when infection sets in. That’s what the problem is with leprosy – it’s not the bacterial disease per se, it’s the result of not noticing that you’ve cut/stabbed/broken/torn yourself, and not taking action to fix the problem, allowing all kinds of other bacteria to get under your skin and in your bloodstream. That’s why leprosy is almost always fatal.

Of course, with the advent of modern antibiotics, Hansen’s Disease could be kept in check almost indefinitely, allowing the sufferers to at least live a reasonable life. But the penalty, even with the antibiotics, is that as sufferer has to continually scan their body for the slightest sign of cuts or abrasions, or worse. This used to be called VSE (visual self examination), and it was a huge drain on your energy and intellect. Imagine having to stop and scan your hands (front, back, in between the fingers, under the fingernails) and feet (top, sole, ankles, shins) – every 20 seconds or so!

So there’s an unfortunate example of what the pain response can help us avoid, by alerting us to the potential for infection or worse, blood loss, bone damage, and so on.

When the Pain Won’t Go Away

On the other side of the scale is what is now called chronic or neuropathic pain.

This seems to be triggered by a major (or minor!) injury, that the nerves for some reason can’t stop sending pain signals for. At the time of injury, the pain was useful for telling your brain that something was wrong somewhere. But, whether you were unable to get treatment for the injury, or if you got treatment, the pain receptors just keep on firing, telling your brain the injury is still there. It’s similar to amputees’ reports of “phantom limbs”. Some amputees can still “feel” their missing arms or legs, or feel itching, or tingling, in fingers or toes that don’t exist any more.

Chronic or neuropathic pain, however, involves much more than just the peripheral pain receptors. It’s now known beyond doubt that long-term receptor firing can cause the whole chain of pain transmission to go “askew”, from the receptors in the skin or muscle, to the pain fibres themselves, to the inter-synaptic gaps and the chemicals that take part in pain signalling, right up past the spinal cord and into the brain.

Worse, as the constant receptor signalling “ratchets up” the amount of pain signalling, the body responds by activating more and more pain transmission channels, and even lowers the threshold of pain, in an awful and unstoppable spiral.

That’s what I’m going to talk about next. That’s what’s happened to me, and that’s why I want to find a way to stop and/or reverse the problem. I know it’s possible to stop the spiral, because every now and then it happens, for a minute, or an hour, or sometimes even a whole day, so there’s something involved that all the so-called “pain specialists” on the planet are missing. Probably because none of them ever felt such pain, but that could just be my bitter take on their inadequacy.

How Pain Works

This is going to get technical. Enjoy the ride!

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