Researchers Discover an "Off Switch" For Pain In the Brain

concertina226 writes Scientists working together from several international universities have discovered that it is possible to block a pathway in the brain of animals suffering from neuropathic pain, which could have a huge impact on improving pain relief in humans. So far, the most successful ways to treat chronic pain from a pharmacological point of view are to create drugs that that interact or interfere with various channels in the brain to decrease pain, including adrenergic, opioid and calcium receptors. However, there is another way – a chemical stimulator called adenosine that binds to brain receptors to trigger a biological response. Adenosine has shown potential for killing pain in humans, but so far, no one has managed to harness this pain pathway successfully without causing a myriad of side effects. Led by Dr Daniela Salvemini of SLU, the researchers discovered that by activating the A3 adenosine receptor in the rodents' brains and spinal cords, the receptor was able to prevent or reverse pain from nerve damage (the cause of chronic pain).

Comments

All or nothing

[TWX]

I'm curious if this'll be an all-or-nothing thing, or if there are degrees of gradation. Pain itself serves good in that it prevents one from doing things that cause it, so we don't injure ourselves.

Also makes me wonder if pain caused by emotion or stress would be affected, and to what degree. It's been said that emotional pain is a physical response, the body literally making itself ill or hurt, so I wonder.

Re:All or nothing

[ColdWetDog]

Doubtful it will be a 'switch' like one thinks about in electronics or logic. It is a complex pathway so there will be plenty of other regulatory and counter regulatory effects. Of interest, is that there are a number of drugs already in trials that work on similar pathways, so it's a bit doubtful that these researchers have found a magic bullet type of thing.

And even if they can shut it off completely in animal studies, it is a long road to developing a useful clinical treatment.

Don't short opium growers just yet.

Re:All or nothing

[bondsbw]

I'm not even going to pretend I RTFA, but I did notice this in the abstract:

Critically, engaging the A3AR mechanism did not alter nociceptive thresholds in non-neuropathy animals and therefore produced selective alleviation of persistent neuropathic pain states.

I'm not sure what it means by selective, whether it is something that can be applied temporarily, or if it can selectively target locations of pain.

Re:All or nothing

[Brad1138]

That could be a very scary thing, snap your leg in 2 or put your hand on a burner and not know it....

Re:All or nothing

[myid]

I'm curious if this'll be an all-or-nothing thing, or if there are degrees of gradation. Pain itself serves good in that it prevents one from doing things that cause it, so we don't injure ourselves.

The article at http://brain.oxfordjournals.or... has a short section titled "MRS5698 does not alter normal nociception". That section says, "MRS5698 tested at the highest effective dose had no effect in tests that measure the acute thermal nociceptive component of physiological pain: tail flick and hot-plate (Fig. 2H and I)."

Wikipedia says,

Nociception (also nocioception or nociperception) is the encoding and processing of harmful stimuli in the nervous system,[1] and, therefore, the ability of a body to sense potential harm.

Any doctors here - does that mean pain from danger still is felt, just not chronic pain from damaged nerves?

Re:All or nothing

[QilessQi]

Yep, CIPA is extremely dangerous. You have to self-monitor at all times:

CIP: http://en.wikipedia.org/wiki/C...

CIPA: http://en.wikipedia.org/wiki/C...

Re:All or nothing

[Anonymous Coward]

This isn't quite the same thing, but there are PTSD treatments that work by numbing the emotional response and then making the person recall a specific event. Later the person will still remember the event in full detail, but they won't experience the associated emotional trauma.

Re:All or nothing

[Anonymous Coward]

Except in the case of PTSD, the symtom is really all that matters.

Re: All or nothing

[Anonymous Coward]

Psychedelics have been proven to treat and even cure PTSD...

But you'd rather see someone on sedatives for the rest of their life than take a dose of LSD/psyllicibyn (in a therapudic setting) and deal with PTSD symptoms permanatly by addressing the root of the problem?

Hell, look into DMT - that can benefit all manner of trauma induced psychological problems.

Or you know... Keep buying pills the rest of your life to minimise the symptoms rather than treating the cause.

BigPharma thanks you!

Re:All or nothing

[fuzzyfuzzyfungus]

It might not work in young children (see also 'congenital insensitivity to pain' and the unpleasant self-inflicted/accidental injuries that children with it wrack up); but as a now more or less mentally competent adult I'd really be in favor of replacing pain with something more informative and less painful. Maybe SNMP.

Re:All or nothing

[Anonymous Coward]

I suffer from chronic pain and I've been taking codeine for the last five years. I hate this stuff, but when I decide to go a day without it (from fear of addiction) then it's horrible. My main problem is recurrent corneal errosion, so the epithelial cells on the surface of my eye stick to my eyelid while sleeping and then get torn off upon waking. It's like having a papercut across your eye every time you wake up.

My pain serves absolutely no purpose other than to make life miserable. If I could switch that off then I would in a heartbeat. There is no significant injury to the eye and it usually "heals" itself in a few hours, but in that time the pain can get up to 8/10. Until someone finalizes that off switch I'll just keep dodging codeine addiction I guess.

Broken hearts be damned. If you want to understand pain go ask someone to throw a book at your eye.

Re: All or nothing

[Anonymous Coward]

Easy there tiger. You're going off half-cocked and hearing what you want to hear. He was talking about a treatment where the emotional trauma of the memories is reduced in the long term by emotionally numbing the patient for a limited duration so that the memories become associated with milder feelings than the ones originally imprinted. Your suggestion of using psychedelics probably has a similar method of action, but they are not contradictory, and the parent post was certainly not advocating that the PTSD survivors be doped up continuously so that we don't have to deal with them/enrich big pharma.

Re:All or nothing

[El Puerco Loco]

It means what it says it means, that it selectively alleviates neuropathic pain, not all causes of pain. Neuropathic pain originates form damaged nerves, is usually experienced as persistent burning, tingling, pins and needles sensation and doesn't respond well to opiates or nsaids.

Re:All or nothing

[El Puerco Loco]

RTFA, it says it selectively blocks neuropathic pain, not pain from all causes.

Re:All or nothing

[El Puerco Loco]

Opiates are ineffective for neuropathic pain. current treatment is usually with antidepressants like tricyclics.

Re: All or nothing

[Anonymous Coward]

Unfortunately, I can guarantee that after five years of using any opiate you are absolutely addicted. A day or two off here and there isn't going to matter. Short acting opiates can hook in less than a week. Doctors are woefully ignorant about opioid addiction. I've been in the trenches man, please think about a slow titration when you're ready to get off, and I wish you well. Opiate addiction and withdrawal is a nightmare.

Re: All or nothing

[Anonymous Coward]

I thought pot was the go-to for eye pain, or was that just a Simpson's joke? Either way, it's less addictive than opiates.

Re:All or nothing

[labnet]

I'd be interested to see if this has an impact on tinnitus, which for most people who suffer it, is like audio neuropathic pain.

Re:All or nothing

[Neil Boekend]

And, very importantly, is now untreatable. "Sorry, just suck it up" isn't something a doctor likes to say to someone in real pain. It's not always "tingling" or pins and needles.

That it is selective is a great pro. You don't want someone with strong phantom pain in their severed hand to loose the other hand due to an infection that wasn't noticed because the painkillers stopped the important signal with the phantom one.
Missing one hand is already problem. Missing two is an unimaginable problem (at least, I can't imagine it).

Re: All or nothing

[Anonymous Coward]

This "PTSD survivor" finds smoking pot to be the most effective treatment.

Re:All or nothing

[Anonymous Coward]

>"Sorry, just suck it up" isn't something a doctor likes to say to someone in real pain.
Misleading. They may or may not like it, but they do it more often than they should because of 'tough love' and addiction hysteria: http://drpullen.com/cant-find-...

Re:All or nothing

[Anonymous Coward]

On the other hand, it would be quite useful to be able to turn off pain if you're being tortured by a psychopath...

Re:All or nothing

[Half-pint HAL]

Hmmm... this sounds like the symptoms I've been experiencing, only more acute. I think I'll get an appointment to see my doctor.

Re:All or nothing

[Anonymous Coward]

Med student here. There are multiple sensory cell types in the skin. From some (temperature, pressure), extreme signals are interpreted as pain. From others (tissue integrity), any signal is interpreted as pain. The experiment mentioned tested either one (thermal) or two (also pressure with tail flick? not clear) of these cell types. I'm not sure what you mean by "danger," but a definitive answer would require testing each cell type for normal generation of signal that should should be interpreted as pain, and ideally also test if the threshold for pain interpretation is unchanged.

To the poster asking about tinnitus below, my understanding is that tinnitus is the result of (inappropriate) auditory nerve signaling or downstream processing in the brain. These are completely different nerves and processing from neuropathy or what are traditionally considered pain stimuli, so I would be surprised at any functional crossover in drug effects.

Re:All or nothing

[bongey]

Chronic pain is much different than regular pain, there is nothing good that comes from chronic pain.Chronic pain is currently ruining my life. It really is almost impossible to do anything and enjoy life while the entire time your back is saying "You want to go for walk today with your wife, fuck you. You want to walk down some stairs hahaha fuck you again"

Re:All or nothing

[hairyfeet]

That is a really good question but I have one to follow up on it...what will the brain replace the feeling of pain with?

The reason I ask is I had a friend who had nerve damage from a car wreck that was always cold and the docs said he wasn't actually FEELING cold, it was similar to how your stomach "hurts" when you are really hungry. In his case his brain was "starving" for lack of a better word so his brain gave him the sensation of always being cold. My late sister had nerve damage in her feet that gave a similar sensation only with her it was her feet was always hot. So my question would be, if you take away the ability to feel pain...what will the brain replace the lost sensation with?

Re: All or nothing

[DigiShaman]

Isn't tinnitus a form of epilepsy? A chronic auditory hallucination.

Re:All or nothing

[earthminion]

Unfortunately I doubt this will stop tinnitus in all people (maybe some, but not all). From my own experiences I've come to think tinnitus sounds like blood flowing in my head that at times I can (unwillingly) focus on very badly (especially when its quiet, making the tinnitus sound extremely loud in my head). Some frequencies appear to be almost resonant, to the point of ringing where they dominate the other frequencies in the sound I'm hearing. I've also noticed when my blood pressure changes, I can hear the difference in the tinnitus. That means the tinnitus in people like me is caused by a mechanical pick up of the sound of blood flowing somehow being picked up when it shouldn't be so loudly picked up. (I suspect I've got a blockage problem somehow in the Eustachian Tube causing it to mechanically pick up the sound somehow, but it doesn't help that I think I can also focus on the sound too well at times now (hard not to, with it being so loud and ever present).

The only practical use I've found for tinnitus is that it now allows me to hear when I should be relaxing more to bring my blood pressure down ... although I would love to stop hearing most of it! ... its useful, but a volume control would be very good. :)

Anyway, this research does make me wonder if they can use it to help reduce so much pain from cancer. If that's possible, it would be an amazing discovery.

Re: All or nothing

[Anonymous Coward]

This is so true. I admire you being frank and honest. Hopefully, your advice will help him . I too, come from the trenches. If he sees this I hope he takes to heart your words and me backing you up. Helping him was my sole reason for this reply. That and commending you.

Re:All or nothing

[Anonymous Coward]

Your shoelaces are loose.
You could lose your loose shoelaces if you remove them from your shoes.
You can lose your keys.
Especially if they are loose.

Brought to you by the letter "O" and the number "1"

Awesome

[Kevin Fishburne]

Still awesome.

Coffee anyone?

[doragasu]

Weren't adenosine receptors blocked by caffeine?

Re: Coffee anyone?

[Anonymous Coward]

All coffee does is make me take a really nasty shit about an hour later.

Re: Coffee anyone?

[Anonymous Coward]

As long as it's not a painful shit, the coffee is working.

Re: Coffee anyone?

[reboot246]

Add a strong source of nicotine and you'll be going even sooner. Try a strong snus like Thunder or Oden's.

Re: Coffee anyone?

[Ol Olsoc]

Add a strong source of nicotine and you'll be going even sooner. Try a strong snus like Thunder or Oden's.

Your body is trying to tell you something.

Hope that it is true.

[Anonymous Coward]

As someone who suffers from multiple radicuopathies ( bad spelling, but root nerve inpinchment) this would be great news. Too bad it will be another 10 years before it is available even if it does work. And another 5 years before it is yanked from the market for causing some fatal illness.

As for the three types methods to treat pain, it's a bit of stretch. Opiates are really the only direct method that works well, Sure, the usage of anti-depressants might work but I find that my mind is a total sieve and the feeling is so bad that I'd rather have massive pain then to be a drooling idiot. As for calcium receptors, i've never heard of these for severe pain. Something I'll have to look into, but since my pain management doctors have never mentioned it I doubt that they work for chronic pain.

Introduction already $$$

[sugarmotor]

Wow, the introduction already goes into the money aspect. They write, "Chronic pain is an enormous unmet medical need with a multi-billion dollar impact on society"

Re:Introduction already $$$

[jd]

Enough about Microsoft! What about those suffering physical pain?

Re:Introduction already $$$

[rtb61]

There is if course nothing more profitable that treating the symptoms rather than curing the affliction, yet they always cry the loudest when they succeed at treating the symptoms without curing the affliction, bless their greedy little hearts. Personally I would like to hear more about stem cell therapy to repair damaged nerves.

Re:Introduction already $$$

[Gavrielkay]

It isn't only about what the pharmaceutical companies stand to gain by selling it. There is major loss of productivity from the folks who suffer from pain like this. Lost work hours, opiates that barely work on the pain but are addictive and damaging, wrecked families due to pain and depression... there's a multi-billion dollar impact alright, and a high personal cost as well.

Re:Introduction already $$$

[RingDev]

Here's the thing, there are some forms of nerve damage that we currently don't have a cure for, there are far more that we don't even understand well enough to have an idea for a cure, and there are some that are so poorly understood, even significant swaths of the medical community doubt that they are real and accuse patients of being drug seekers.

For example: Fibromyalgia. It isn't a disease in it's own right, it is a classification of a set of symptoms that have not been able to be attached to a source. There are lots of theories and progress is being made in the field. But when the causes could be genetic, dietary, environmental, psychological, or even sleep related, any step forward could be helpful for some subset of FM sufferers, but leave the rest without aid.

If this approach can be made to work, it would mean that virtually all of the FM sufferers in the world could lead a normal life, while at the same time research continues on the underlying causes of their conditions.

When you wake up every day and have to see your spouse, your child, or your friends in agony because for no meaningful reason their brain decides that they should feel like every joint is coated with sandpaper, that every muscle is strained and torn, that every tendon is inflamed, then any option, even one that profits some greedy ass in a suit, becomes a miracle.

-Rick

Re:Introduction already $$$

[Anonymous Coward]

Man, I hope everybody screaming about stem-cell or transfected gene insertion or whatever to cure human ailments never breathes a word of criticism about genetically-modified organisms. If they want people "modified", who cares about tomatoes...

Re:Introduction already $$$

[rtb61]

Pretty insensitive aren't you, I thought you would have guessed why I had a preference for cure over symptoms. By the way I found the best way to handle pain, was to put up with it during the day and only take pain relief in the evening. This allows natural pain relievers to continue to be produced and helps to prevent tolerance to analgesics developing. So an uncomfortable day but maximum relief at say tea time and before going to sleep, especially when the analgesics combine with natural pain relievers which you are still producing in quantity. Getting full relief in the evening and when going to sleep does a lot to help deal with next uncomfortable day.

Re: Introduction already $$$

[Anonymous Coward]

If you can just "put up with it," then you aren't really in that much pain. Worse, you are unable to relate to people who are in severe pain, because you think that your little ache is as severe as what others suffer.

Fibro myalgia and Ehlers-Danlos syndrome are good examples. They're rare and regularly misdiagnosed due to not having a good way to test. They also lead to extreme pain. But most people have a headache or a sore muscle, and think that pain is just a minor deal addressed by "sucking it up." :/

We already know this...

[Freshly Exhumed]

Vulcan Science Academy has been studying this going back to the time of Surak.

Re:We already know this...

[Anonymous Coward]

Citizens of The Culture genetically engineered human bodies to switch off pain millennia ago.

Re:We already know this...

[Anonymous Coward]

"My head hurts."
"That's your own stupid fault for falling over a tree stump. Turn off the pain."
https://www.youtube.com/watch?v=ET8IFxPo61w

Re:How about the homosexuality switch?

[Anonymous Coward]

Ashamed you're not gay enough?

Ending pain

[Thanshin]

This is one of the big frontiers of humanity.

There is little a person won't do to stop pain. A simple way to stop it with no consequences for the person nor society would solve a huge lot of other problems.

Combine this with Fear switch

[Champaklal]

There's part of brain to feel fear of anything. switch that part off too, and you make humans dangerous species.

Re:Combine this with Fear switch

[wonkey_monkey]

Really. You don't think fear makes humans dangerous?

Re: Combine this with Fear switch

[Anonymous Coward]

Because we aren't already...?

Re:Combine this with Fear switch

[jbmartin6]

I don't know about angels, but it is fear that gives men wings.

Re:Combine this with Fear switch

[wonkey_monkey]

No, that's Red Bull.

Re:How about the homosexuality switch?

[pushing-robot]

"My mates and I could never get laid, but then we discovered Homify."

Re:Pure evil

[Anonymous Coward]

You sound like the sort of idiot whose tune will change in a hurry as soon as you or one of your ill-advised loved ones experiences a condition requiring chronic pain treatment.

Self-medication

[Anonymous Coward]

I bet that it'll be made highly illegal for anyone to self-medicate under the auspices of 'caring'. No one should have to go on the black market for self-medication...

But, as someone who switches between opiates and kratom (SSRIs suck), I'd happily live on another pain killer/anti-depressant if it's better, assuming that this kills emotional pain and keeps me functional like they do.

(Also I'm not asking for and don't want any /.er's medical advice. Please don't bother.)

Re:Self-medication

[Anonymous Coward]

Incoming, unsolicited medical advice! Drink a glass of water.

Re:How about the homosexuality switch?

[Anonymous Coward]

You almost made me spray wine all over my keyboard, you insensitive clod!

If you could give me a pill that made me a boy, I would probably take it, since that's what my reproductive system is.

But then I'd just be a g4y man.

If you could give me a pill that gave me the ability to be in lesbians with another woman, I might consider backing off my anti-androgen and attempting reproduction.

Spiral on, science! Your drill will be the drill that conquers the heavens!

Re:How about the homosexuality switch?

[Anonymous Coward]

Spiral on, science! Your drill will be the drill that conquers the heavens!

God: "The humans aren't observant enough! To punish them, I'm eliminating sex!"

Why don't they study the cause of the pain ?

[Foske]

I am the last to say chronic pains are not real, but I do know that chronic pains are most of the time a symptom of something else, and way too many people are diagnosed with chronic pains. Doctors say they can't treat something and you have to live with it, though many times that is simply wrong. My wife was diagnosed with 'chronic pain' by 6 independent doctors. Number 7 said she should stop drinking milk. Pain is almost completely gone. I myself have been walking around with Irritable Bowel Syndrome for years. Stopped eating Gluten and the Syndrome is gone.

We have way too many "diseases" which are nothing but a name for clueless doctors and a failing medical system. My basic rule is: If you broke something: Go see a doctor. If you have something that's a bit more vague: See someone who understands how the human body works. And yes, I now refer to for example good acupuncture, chiropractic or homeopathic doctors. Unfortunately you also have a lot of crap there.

Mindfulness is the best pain killer

[Anonymous Coward]

Have only been meditating for a year now and amazed at the ability to accept that pain is all in the mind. Two simple questions I mentally ask myself when encountering pain immediately reduce the severity. "What shape is this pain?" and "What colour is this pain?". Studies have proven that experienced meditators have the highest pain threshold ever recorded, it's a shame my western education made me discount the power of meditation and promoted the use of medication. I'm not completely against medication, but do see our overuse of it is a problem.

Re:Mindfulness is the best pain killer

[ITRambo]

Meditation leads to relaxation which results in less perceived pain. Try meditating while under a stressful timetable and focusing on the job at hand so the work is completed ASAP while the next job awaits, all while arthritis is causing your joints to beg for a massage that isn't coming. This is why we take analgesics. Meditating isn't often practical when pain relief is needed the most.

Re:Mindfulness is the best pain killer

[Half-pint HAL]

But if you eliminate the fear of pain, that's most of the distraction gone.

But....

[Anonymous Coward]

Does it work for a pain in the ass?

Which makes me wonder...

[Anonymous Coward]

How many 'on' switches did they hit before finding it?

That's the reason why you're addicted to coffee

[moxsam]

Coffeine blocks adenosine receptors, and in turn their numbers multiply, reaching an equilibrium after just 2 weeks of regular coffeine intake. Stop taking coffeine, and you're going to feel pain (mostly headaches and rheumatic pain) 18 to 22 hours after your last dosage. Not to mention being sleepy, depressed and so on. The adenosine builds up as usual in your body after you wake up as a by product of normal neuronal activity, but it just keeps on binding to all those extra receptors. Ouch!

Depending on how heavy your coffein addiction was it takes weeks to months to feel like a normal human being again. If they want to mess with that system, good luck. Finding a drug that causes no withdrawal symptons, good luck.

Re:That's the reason why you're addicted to coffee

[Anonymous Coward]

There's a similar mechanism behind how opiate addiction works, and that's why withdrawal from that is one of the worst things ever.

I guess it'd be more useful, if possible, to find a way to block the brain from making more receptors and from manufacturing antagonists for those receptors so one can keep getting the same effect from the agonist. (A cure for tolerance and for chemical dependence? They'd never fund it. They're more concerned with 'blocking pleasurable effects'.)

Captcha: sinister

This is not news

[DrJimbo]

I figured out how to disable beta months ago.

Morphine

[ThatsNotPudding]

"Someday, they'll be a Cure For Pain.
That's the day I throw my drugs away." RIP, Mark Sandman

But...but...

[JasonGoatcher]

Don't you see? We don't actually WANT a replacement for marijuana. Why can't you just let us smoke our weed in peace?

Full disclosure:I don't smoke or take drugs, but I think cigarettes are WAAAAAAAYYYY more dangerous than weed, considering the normal usage patterns.

Re:But...but...

[Impy the Impiuos Imp]

Does it actually help people with, say, burning stinging diabetic feet?

Re: Great! That eases pain from anal sex!

[Anonymous Coward]

A classic case of projection.

Welcome to 15 years ago.

[Anonymous Coward]

ABT-702 (4-amino-5-(3-bromophenyl)-7-(6-morpholinopyridin-3-yl)pyrido[2, 3-d]pyrimidine), a novel orally effective adenosine kinase inhibitor with analgesic and anti-inflammatory properties: I. In vitro characterization and acute antinociceptive effects in the mouse.
Jarvis MF, Yu H, Kohlhaas K, Alexander K, Lee CH, Jiang M, Bhagwat SS, Williams M, Kowaluk EA.
J Pharmacol Exp Ther. 2000 Dec; 295(3):1156-64.

http://www.ncbi.nlm.nih.gov/pubmed/11082454

Aluminum and Fluoride

[Anonymous Coward]

Maybe, if they increase the amount of aluminum being sprayed into the atmosphere to shield electronics and digital avionics from radiation of the sun and maybe, if they increase the amount of sodium fluorosilicate, which is a poisonous by-product of the aluminum manufacturing process, being dumped into the water supplies around the world, we will all just forget we are in pain from the scientifically proven effect aluminum has on brain function, blocking electical firing of the neuropses. Now, what were we talking about?