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Why Can’t We Make Better Painkillers?
I asked this question on Fred’s post about the problems his family’s had filling his mom’s prescriptions for painkillers — medication she needs to treat the pain of advanced lung cancer. Moments after asking it, I began thinking, “Hey, wait — that’s a good question.”
Or maybe it isn’t, but I figured there could be no harm asking, because I bet I’m not the only one to wonder.
Why is it that the only really effective painkillers we seem to have are highly addictive and dangerous drugs that addicts love? The point of a painkiller is to make the pain go away, not to get you high, so why do we not yet have a class of drugs that only do the former? Or, to wit: We already do have many of them, such as aspirin, acetaminophen, and ibuprofen. And those are great, effective drugs, as anyone who’s had a headache or a sprained ankle knows. But apparently, they’re not effective enough to treat more serious pain.
So for those of you who know more about medicine, pain management, and drug development than I do: What’s the problem?
It seems to me that the long-term solution to the problem Fred and his family are confronting — one my family has also confronted, and I’ll vouch for the horror of trying to secure effective painkillers for a terminally ill relative and being treated like a common drug addict for doing so — is to create a better class of painkillers. We clearly need painkillers that treat pain but are of no special interest to people who want to get high.
In other words, isn’t this a medical research problem?
Can anyone here shed any light on the obstacles to creating that kind of drug? Is anyone close to doing it? Are any such drugs in testing? If not, who’s doing the most interesting research into the problem?
It seems to me the market for such drugs must be absolutely massive — if we consider “pain” a disease, it’s one we will all, almost certainly, face sooner or later. And short of dementia, I’d guess it’s also the one most of us most fear. Most of us would pay almost any amount of money not to experience terrible pain, or worse still, see a loved one in excruciating pain. So I can’t imagine there are no financial incentives to drug development: an orphan disease, this is not.
An effective painkiller that posed no risk of mental impairment or addiction would be (I would think) one of the most profitable drugs ever manufactured. It would leave Viagra in the dust. It would inherently be an obvious social boon, with a very significant secondary social benefit: There would be no reason strictly to control or limit its prescription.
Why is this problem so difficult, medically? Is the obstacle a known and thus-far insoluble medical one? Or is it a political, regulatory, or economic problem? Is it somehow related to the drug development process?
Does anyone here know?
As I was writing this, another question occurred to me. What would be the obstacle to creating drugs that get people as high as the opiate painkillers do — if that’s what they want to be — but that don’t impair mental functioning and judgment, and aren’t as likely to kill them if they overdose? Why, in other words, aren’t we fighting a war for drugs — much better ones?
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This is something I’ve wondered repeatedly. I imagine it’s easier said than none, but it seems like an incredibly worthy project. It’s sad enough that so many people need the escape serious intoxicants offer, but it’s tragic that it so often comes at such a high price.
There are some. Tramadol is a step stronger than the over-the-counter stuff, but is not narcotic. Gabapentin is helpful for nerve pain. For really severe pain, though, these are not enough. I’m not an expert, but I think the road block is that any really effective pain killer has to mimic the effect of natural chemicals such as endorphins, and bind to the opioid receptors in the central nervous system. Doing so makes them addictive. So Claire’s challenge is a bit like trying to invent water that isn’t wet.
That makes sense — although again, not being an expert, I don’t know if it really makes sense. I guess I mean, “That sounds good.” But here’s my question. Endorphins, per se, don’t make people mentally confused and judgment-impaired: If they did, we wouldn’t allow long-distance runners to drive. Something else is going on with the way these drugs work. What is it?
And I assume pain takes place along a complex series of pathways, not just the opioid receptors. How does aspirin work, by contrast? Why can’t we make a super-aspirin?
Are we aas conservatives allowed to question the pharmaceutical industry?
I have questions about vaccines myself. But when I bring it up around my conservative or Republican brethren they throw me the kook label and shut down the conversation. Pure political correctness.
I mentioned it during the RICO live blog of the debate after Trump got the question, and I started getting hammered (apparently Trump has a natural immunity to that treatment that we really should extract and turn into a vaccine).
Another thought just occurred to me. If anyone is apt to fund, develop, and test painkillers like that, it will be our government. The military, in particular.
War is hell, but we owe modern medicine to it.
Of course. But what’s your question? I’d love to have someone who works in that industry reply to mine.
Do we have any Ricochet members who do?
Journalists probably don’t come any more clear-eyed and disinterested then Sharyl Atkisson. She’s done some reporting that vaccines aren’t as entirely safe and benign as we are led to believe.
Perhaps it is that so many anti-vaxxers come across as such flakes, for want of a better term, that a dispassionate discussion of the actual risks of vaccines seems impossible.
All 5 of my children were vaccinated according to schedule. I accepted there was the risk of a reaction and other unwelcome side effects. I wouldn’t have done it any other way. But I didn’t kid myself into thinking nothing could possibly go wrong.
“It seems to me that the long-term solution to the problem Fred and his family are confronting — one my family has also confronted, and I’ll vouch for the horror of trying to secure effective painkillers for a terminally ill relative and being treated like a common drug addict for doing so — is to create a better class of painkillers. We clearly need painkillers that treat pain but are of no special interest to people who want to get high.”
Great title question and several great points, but I disagree with the point in the paragraph above. The problem Fred and his family, and similar others, face is not that there are no non-addictive painkillers. It’s that the state is in their way. Creation of non-addictive painkillers would very likely lead to the state not interfering, but so would the state not interfering in something that’s one of its business.
When I first joined Ricochet, I spent a couple of days reading all the posts and comments on vaccines. I was very interested in what people thought about them. I just ran a Google search on the site. There has been a lot written here about vaccines.
Well I think to get at the question Claire poses we need to think about what pain actually is, in a physiological sense. Pain is the result of the over stimulation of sensory neurons. Over stimulation that is often caused by tissue damage of some kind. The means to alleviate pain are to either remove the causing stimulant or block the signal from these neurons. Ideally we seek to fix the cause of the signal ie. reduce swelling, reset bones, remove obstructions, allow tissue to repair etc…ultimately this the the goal in medicine, as pain is a symptom indicating an actual problem.
Now, some conditions are currently beyond our means of treatment, meaning the only means to deal with the pain is to try to short circuit this natural bodily response. The way to do that is to dull the nervous system by over stimulating it with chemicals whose action is not interpreted as pain by the brain. In essence you are drowning out the pain signal with a new signal. Unless our brain chemistry changes the kind of chemicals that will be able to do that will be limited to these addictive substances.
The other alternative I can see is that you literally block pain signals from reaching the brain by somehow impairing the function of the sensory nerves. We do have such substances and techniques, but the danger of their application in chronic conditions is that this is a step much a kin to amputation.
The ideal pain management system would be to have a means of short circuiting the nervous system signal prior to it reaching the brain. This would not be addictive and it shouldn’t cause endorphin release. The problem is that such means might also impair signals going from the brain to the body. Essentially some forms of spinal chord damage would offer the non-addictive pain relief that someone suffering from long cancer might desire. But, obviously becoming a quadriplegic does not seem like the desired answer to the problem.
I’d be curious to know why … amputation is permanent, but drugs, presumably, are taken on a schedule. I can see why using a total nerve block would be undesirable if you want to use the part of the body from which the pain originates, but what are the obstacles to creating a medication that partially blocks the signal? And in the case of pain that emerges, say, from the lungs or the stomach — why would it matter if one didn’t have full conscious control over the way that region of the body functioned?
I assume that these are naive questions and that the answers are obvious to people who’ve thought about it more, but I truly don’t know.
When I was younger I pondered this question as well a lot. My thoughts were pretty basic though, like why can we not just simply eliminate pain with some drugs rather than just numb our senses (it seemed inefficient at first glance). To be honest though the answer is that all creatures have limits (you can never actually eliminate pain) and we have only finite knowledge and resources, we have also not exactly fully applied them to medical research.
The reason why we have not is because there are some rather high bars at the FDA to jump over. All drugs alter how our bodies work (technically even food is a drug) and at the FDA in order for a drug to pass it has to have a .001% rate of death if I remember correctly and there are other obstacles as well and this make it so pharmaceteutical companies have to spend extra work on limited avenues of drugs for years in order to create a drug that might have value and not kill 1 in a 100,000.
The reason why anti-vaxxers get laughed at is because the first published study (and only study to my knowledge; scientist’s name was Andrew Wakefield) that supported their hypothesis was one in the 90s in England and it went through only 19 subjects, had no control group (generally speaking you need at least a thousand to be at a reasonable error rate of 3% and you have to have a control group for crying out loud!) and found a link between some vaccines and children developing autism.
The issue was that when others tested the same hypothesis at the same and larger scales of test subjects they were unable to reach the same results. Since the results could not be repeated to the same conclusion that meant something had differed then in the methodology. After an investigation they found the man who had conducted the 19 person study had in fact been compensated with 500,000 dollars by trial attorneys in England so as to create demand for law suits against companies. Overall, the anti-vaxxer argument has no grounds, not even at inkling.
Of course they also might say that autism has been diagnosed at higher levels now right? Vaccinations have been standard in the USA for at least 50 years, so I think we should have seen the trend then. The reason why we have seen an uptick is probably an increase in awareness and diagnostic criteria. Akin to our discovery of impairments from cancer to AIDs the scientific community is finding “new” diseases that had been misdiagnosed before.
No they are good questions, I’m though doubt I am know enough about this to really answer your question. To me it seems that the problem with drugs and affecting tissues like the lungs and stomach is that it is hard to get to these places without first getting to every other place. The means of administering drugs to reach them is through the vascular system. This will mean that you expose everything to the drug. I don’t know if sensory nerves are distinguishable from each other. Ie. the nerves that feel pain in your stomach are the same kind as those that feel pain in your foot. Therefore you can’t shut one down without targeting the other.
The further danger of trying to reach internal tissues with nerve blockers is that you have to be carefully not to damage the the nerves that the brain uses to coordinate your unconscious actions, like breathing. You have to remember functionally the electrical signals between your various neurons can’t be all that different, and your brain uses them to coordinate things like breathing and heart rate without your consciousness. This is why some people who suffer sever neck injury can loose lung or even heart function.
Are they? There are nerves around the foot, right? While I can see why an oral medication wouldn’t be selective, what about an injectable medication? Or a medication that can be coated, programmed, swallowed, and controlled remotely so that the coating only dissolves when it reaches a certain part of the body?
And is it true that pain signals are the same kind of signal as others that travel up the nerve? Why do we experience them as different from all the other signals if they’re in fact the same? Surely there’s … some kind of difference, right?
Sure … but our brain does do that. It can tell the difference between “You’re in pain” and “You need to take a deeper breath.” So there’s obviously some difference in the nature of the signal.
I’m sure not saying that I understand this at all or that I have a good idea for solving it: I’m just curious about how the people who do think about it, and where the R&D effort is being directed right now. (I’m sure there’s plenty of R&D. I just don’t know much about it.)
My first response to Claire’s question was, “There’s no such thing as a free lunch.” I’m convinced that’s the case, even though I have no particular knowledge in this area (although I have more experience with neurological issues, medications, and whole-body effects than I’d like).
No, but there’s certainly such a thing as “massive advances in medicine.” Probably all of us here can credit our lives to one or another of them.
Well I think a lot of the difference isn’t in the nature of the signal but rather where that signal ends up in the brain. Which is who people can have misinterpretation of sense when they suffer brain damage. Both sound and sight signals are converted into one kind of input. They just go to different areas to be interpreted if something crosses the wires, you can start hearing colors, and seeing music.
Definitely. I think your’s is a good question, but I suspect we’re a long, long way off from being able to tease apart the ill-effects on body and brain of otherwise efficacious treatments for pain — if it’s even possible to get there from here.
In the meantime, it’s probably much easier (although not easy) to try to deregulate the pharmaceutical industry.
That’s just my guess.
There are pain killers that work differently from opioids, but any time you take a medication there are going to be side effects. Ultram (Tramadol) is a an opioid that has fewer side effects, but is used to treat moderate pain, which is problematic when trying to address sever cancer pain. Toradol (Ketorolac) is a wonderful NSAID that provides great pain relief without the negative side effects of opioids, and it’s nonhabit forming. The problem with Toradol is we only give it for a short period of time, and typically not to older people because it’s damaging to the kidneys and can cause some heart issues. For severe pain, opioids are the best option because of their strong affinity for pain receptors; however, when these receptors are activated, you get a lot of negative side effects. When an opioid binds with a receptor in the synaptic cleft, the transmission of pain signals is decreased. With continued use, other channels begin to open up, allowing those pain signals to increase, and the number of mu receptors decreases, which is why it takes greater amounts of medication to achieve the same effect.
What determines where the signal ends up in the brain? Let’s leave aside the complicated philosophical mind-body problems and assume it’s completely mechanical. The “pain” signal is, obviously, going along a path that at some point diverges from the “tastes great” or “oooh, warm and nice” signals, right? Mechanically, there’s some place at which they separate, whether it’s in the foot, along the spinal cord, or in the brain itself. It has to be, doesn’t it?
Where? How?
Which again suggests to me that in principle, pain signals could be converted to pleasure signals. Or nice music. I’m not saying, “And that would be easy to do, and free of risk,” I’m just curious to know whether anyone’s doing research along these lines.
During my surgical rotation, anesthesia did a lot of nerve blocks for patients undergoing surgery on their extremities. I have had patients that will also get nerve blocks in their back for chronic back pain. Implantable pain pumps are also available, but they use opioids.
The reason why opioids are addicting is because of the up and down regulation of receptors that happens with extended opioid use. The patient becomes tolerant and then develops physical dependency.
Someone may develop non-opioid meds that work really well for severe pain (like cancer pain), but there will always be side effects.
My two cents as someone who suffers from chronic pain (Reflex Sympathetic Dystrophy [RSD] or Complex Regional Pain Syndrome [CPRS]) is there are different types of pain and what may work for the type of pain I have will not work for others and vice versa. Opioids are completely worthless for me (thank God because I don’t handle them well) but I have had some success with anticonvulsants like Lyrica and Topamax. The best treatment to date for me is a neurostimulator I have implanted which sends an electric signal to a specific area of my spine to block the pain signal and replace it with a tingling, asleep sensation.
I think that’s considered a medical truism — I’ve never heard otherwise — but again, I wonder why it has to be so. I mean, no one ever says, “Careful with that WD40 — it fixes everything, sure, but there are going to be side effects.” Why is a human body so different from a mechanical object?
I was given Ultram when I injured my forearm (a Ricochet overuse injury, by the way). I thought it was useless compared to ibuprofen, so I can certainly see why it wouldn’t be the drug of choice for cancer patients.
That’s prescribed all the time in Europe. In fact, I think it may even be available over the counter.
Are there any promising drugs in testing that seem to like those pain receptors? Or is the problem the very fact that they work, and that therefore the rest of the brain quickly starts to compensate for the loss?
Is there any known way to boost the number of mu receptors? Is anyone trying to figure out how to do that? Could that be done, perhaps, in conjunction with the administration of opiates — to reduce the tendency to develop a tolerance?
Glad to know the thought I had (see my comment above) wasn’t totally crackpot. So that does seem to be a good idea. Why wouldn’t that work for people with cancer pain? Or postoperative surgical pain?
So to my second question — why can’t we develop drugs that get people high, if they want to be, but don’t impair their functioning and judgment and don’t involve the high risk of overdose — what would be the obstacles to doing that?
Do we fully understand, or even partially understand, what it is about the opiates that makes people feel good? It’s obviously not just the absence of pain, right?
There are receptors primarily in the spine, but also all over the body, and that’s why you get miosis, constipation, and respiratory depression.
The body doesn’t work like a machine. Our chemistry is complex. GABA inhibitors like gabapentin and lyrica are great for nerve pain, but also not without side effects.
There’s nerve pain, which is treated one way, and musculoskeletal and visceral pain, which is treated another way.