Eternal Sunshine Drug Points the Way Toward Counteracting the Agony of Chronic Pain

[AlphaMethylPhenyl]

One of brain researchers’ closest brushes with science fiction in the last 10 years came with the discovery of a chemical that could completely wipe out memory, a molecule that evoked a real-life version of the scenario depicted in the film Eternal Sunshine of the Spotless Mind, in which a couple undertakes a procedure to erase their memory of each other when the relationship falls apart.

Fortunately, the artificial amnesia occurred only in laboratory rats. But the experiment raised an obvious question: What would anyone do with a drug that essentially reformats your mental hard drive?

Who would be interested besides a neurotic Woody Allen trying to reboot his life, or a sadistic Josef Mengele type attempting to conduct the kind of scientific experiment that would be judged a war crime at The Hague?

A group of researchers have now come up with a more pragmatic answer to this question than incorporating the memory-erasing agent as a plot device in a cyberpunk novel

Neuroscientists at McGill University and collaborators have just reported in Molecular Pain that the chemical with the evocative acronym ZIP can selectively wipe out the nervous system’s “memory” of the chronic aches and pains that plague about one in four North Americans, apparently leaving other memories intact.

Pain that persists more than a few minutes leaves a memory trace—that’s why just a light touch is sometimes enough to produce a yelp of agony months after an injury. The archetypal example is the soldier with an amputated leg whose phantom limb still aches years after being severed.

In the experiment at McGill, ZIP administered to the spinal area of rats wiped out pain memories in hind paws that had become tender and hyper-sensitized from the application of capsacin, the compound that produces the burn of chili peppers.

ZIP is the Eternal Sunshine chemical that was spritzed into the memory-forming locus of rat brains to make the animals forget their past. One of the McGill co-authors, Todd C. Sacktor of SUNY Downstate Medical Center in Brooklyn, led the original research that discovered ZIP (zeta inhibitory peptide) along with the memory-preserving enzyme PKM-zeta, which it inhibits.

Years of experimentation and testing would be required to determine exactly where it should be administered to selectively wipe out pain memories without obliterating a lifetime of family recollections. And even then, ZIP will never be an over the counter drug. To be used in medicine, it would need to be injected into the spinal cord to reach the neurons involved with storing the pain memory.

Still, the experiment will leave neuroscientists with a better understanding of the molecular players involved in establishing pain memory. “It gives a clue as to a potential target for influencing persistent and chronic pain,” says Terence J. Coderre, a professor of anesthesiology and neuroscience at McGill who headed the research team.

Even if ZIP never makes its way down the lengthy drug development pipeline, it lays the groundwork for other chemicals that could permanently annul the pain memory that results in the persistent discomfort that turns walking, sitting or even lying down into a daily ordeal for so many.

http://blogs.scientificamerican.com...gony-of-chronic-pain/?WT_mc_id=SA_WR_20120222

 

[Gyrospeck]

Scary stuff.

I don't like the idea of creating artificial amnesia for medicine or anything else. The potential for misuse (intentionally or not) is far too high. I'm not sure if I support the idea even if used completely properly. Erasing our personal pains in this kind of manor could create pockets of forgotten poverty. Imagine if an impoverished person uses this technique to feel better. Would this person still remember or care enough to fight for their friends and family? This treatment has the same problems that depression and anxiety treatments currently have, but is far more extreme.

Medicine should be focused on environment and society first. What is the point of erasing the memory if the environment remains?

 

[Flynnal]

Medicine should be focused on environment and society first. What is the point of erasing the memory if the environment remains?

Absolutely, I'd agree with the former. However, with the latter, what if the environment has changed and the source of the anguish is no longer there, and the person has to suffer from PTSD for the rest of their lives because they are denied a way to erase those bad memories?

I'd say go for it. We've had enough PTSD, myself included, to put up with any more of this distress.

 

[Druidus]

There are very few individuals, IMO, that would be greatly benefited by such a drug.

But there are some with serious issues it might help, I suppose.

The drug has great potential for misuse, though, at least in some cases.

 

[Foreigner]

http://www.cbc.ca/news/technology/story/2011/05/26/science-drug-memories-ptsd.html

A few years ago I read research on trials being done in Montreal, Canada for PTSD. They first get the survivors of major trauma (like rape, assault, living in war zones, etc.) to write down their experiences in vivid detail. Then they get them to read their account aloud as it is recorded. They then give them a certain kind of drug and have them sit in a quiet room while hearing the recording of their own verbal account of events.

Apparently the way memory works is that when you try to remember an event, certain neurons reach for each other to make the connection which causes you to remember. You know how sometimes you are struggling to remember something, and a few moments later you have the "Aha!" feeling? It's because the nerve bundles that coordinate the memory finally meet up.

In the trials, the drug actually prevents the neurons governing the specific event from meeting up so long as the traumatic event is being focused on, so that over repeated sessions, the memory of the event becomes more and more dull to the point that it no longer effects you when you try to recall it. It's not induced amnesia, but more like a softening of the recollection so that you don't feel like you are re-living it over and over again.

I have a problem with this though. Memory is not just in the brain, it's in the body. If you're a rape survivor, your emotions and body are averse just as your brain is averse. What happens if the memory is dulled or erased but your body remembers, so you are having panic attacks but no longer remember why?

This amnesia therapy is treating a symptom: the flashbacks. The goal of most standard PTSD therapy I know about is integration, not erasure. The jury's still out though on whether or not erasing the memory would actually heal the disorder. Erasing the memory is not really resolving what happened, it's just removing your participation from it. A therapist I met at a conference a couple years back said there is also the school of thought that revisiting memories and re-living the trauma is not a useful means of therapy anyway. You need to alter behaviour on a go-forward basis with positive reinforcement.

 

[Druidus]

http://www.cbc.ca/news/technology/story/2011/05/26/science-drug-memories-ptsd.html

A few years ago I read research on trials being done in Montreal, Canada for PTSD. They first get the survivors of major trauma (like rape, assault, living in war zones, etc.) to write down their experiences in vivid detail. Then they get them to read their account aloud as it is recorded. They then give them a certain kind of drug and have them sit in a quiet room while hearing the recording of their own verbal account of events.

Apparently the way memory works is that when you try to remember an event, certain neurons reach for each other to make the connection which causes you to remember. You know how sometimes you are struggling to remember something, and a few moments later you have the "Aha!" feeling? It's because the nerve bundles that coordinate the memory finally meet up.

In the trials, the drug actually prevents the neurons governing the specific event from meeting up so long as the traumatic event is being focused on, so that over repeated sessions, the memory of the event becomes more and more dull to the point that it no longer effects you when you try to recall it. It's not induced amnesia, but more like a softening of the recollection so that you don't feel like you are re-living it over and over again.

I have a problem with this though. Memory is not just in the brain, it's in the body. If you're a rape survivor, your emotions and body are averse just as your brain is averse. What happens if the memory is dulled or erased but your body remembers, so you are having panic attacks but no longer remember why?

This amnesia therapy is treating a symptom: the flashbacks. The goal of most standard PTSD therapy I know about is integration, not erasure. The jury's still out though on whether or not erasing the memory would actually heal the disorder. Erasing the memory is not really resolving what happened, it's just removing your participation from it. A therapist I met at a conference a couple years back said there is also the school of thought that revisiting memories and re-living the trauma is not a useful means of therapy anyway. You need to alter behaviour on a go-forward basis with positive reinforcement.

It is true that the body retains some type of memory of certain events, in some cases. But generally it is the brain that controls the body, and if you can change how the brain functions, you can also change the body.

What worries me more is the question of HOW they plan to isolate this memory erasing to ONLY traumatic or painful memories. It is concerning, because I'd think that any attempt to use this will be plagued by side effects caused by wide action in the brain.

 

[Black]

A therapist I met at a conference a couple years back said there is also the school of thought that revisiting memories and re-living the trauma is not a useful means of therapy anyway. You need to alter behaviour on a go-forward basis with positive reinforcement.

i know a therapist who says exactly the opposite. if you don't get to the root of the problem and just "alter behaviour on a go-forward basis with positive reinforcement", you may cure the original symptoms but the original problem will always resurface with a different and often more debilitating set of symptoms. it really depends on who you ask, and what school of therapy they adhere to.

 

[ro4eva]

There's definitely been more than a few traumatic events in my life which I'd like to forget completely if I could.

 

['medicine cabinet']

Thats a scary sounding drug but amazing at the same time.

 

[Rob27shred]

This is most definitely a scary Idea to me. I can see how the idea of "erasing" pain or painful memories can be alluring. But even if they manage to make it medically useful where it don't wipe out all your memories I can still see a lot more bad coming from this than good. Like people have already mentioned you could end up with people who have severe pain or mental issues with no idea why they are having these issues. Or even worse this drug could completely wipe out people's memories & god knows what would be left of someone after that. I think our memory is something that should never be "erased" or altered in any way as that is what makes us individuals. I have a ton of traumatic & bad memories but I would never erase them if given the opportunity. If you really think about it too, I bet erasing a traumatic event from your memory would cause a ton more mental problems than just leaving it. Especially if it is a very traumatic experience that has dominated a persons thoughts. I just don't see the brain or body reacting in a good way to having pain or memories "erased".

 

[Foreigner]

What I want to know is where the memory is in your brain if you don't remember it until certain neurons connect? What's happening between your desire to recall something and then the neurons connecting to make you remember? I don't get it. If a drug can disrupt memory recall by blocking neurons from re-connecting, then what "force" is prompting those neurons to search for each other again in the first place?

I just don't get how neurons connecting equals a memory of something.

i know a therapist who says exactly the opposite. if you don't get to the root of the problem and just "alter behaviour on a go-forward basis with positive reinforcement", you may cure the original symptoms but the original problem will always resurface with a different and often more debilitating set of symptoms. it really depends on who you ask, and what school of therapy they adhere to.

Maybe it depends on the individual patient rather than the philosophy. I'm sure both are right, depending on which PTSD patient you look at.

 

[Druidus]

What I want to know is where the memory is in your brain if you don't remember it until certain neurons connect? What's happening between your desire to recall something and then the neurons connecting to make you remember? I don't get it. If a drug can disrupt memory recall by blocking neurons from re-connecting, then what "force" is prompting those neurons to search for each other again in the first place?

I just don't get how neurons connecting equals a memory of something.

That's because it isn't neurons connecting that causes the experience of memory. The capacity for memory recall isn't gained by connecting neurons, not in itself. Memories are coded in the connections of neurons AND in PATTERNS of firing. One neuron may be involved in quite a few memories, and it is the pattern of many neurons firing in this connected set that causes our experience of remembering.

Memory is a relative and tangential thing, as well. We don't usually choose to remember something; usually it is simply related to something else we're thinking about, some other stimuli, and the recall is automatic and unintentional.

Think of it this way, though it's quite simplified:

Three neurons are connected in a set, with N1 connecting to N2 and N3, and N2 connecting only to N1 and not N3. They encode the memory of the time your grandmother made you an apple pie when you were a child. Each one is connected to other neurons relative to the information they encode. N1, for example, connects to the other neurons coding for the properties of apples, N2 connects to others involved in coding the properties of your Grandmother, and N3 connects to others involved in cooking. This set, N1, N2, and N3, have the potential to give you an experience of remembering your Grandmother's apple pie, and have a chance of firing as a group when stimulated by something(say, you eat an apple while thinking about your Grandmother, stimulating N1 and N2 which also stimulate N3).

But you don't remember your Grandmother's pie JUST because these three neurons are connected, or even just because they're all firing. It is a much more complex phenomenon than that. Rather, they must fire in sync according to the pattern that this network formed with. N1 must fire a certain number of times per second, while N2 fires faster/slower, and also while N3 fires in a specific way. Then, when the networked neurons are all firing at the right rate to each other, the memory of your Grandmother's pie is spontaneously generated in the brain, and you experience the recall of information about this.

From one memory, the potential for others arises. Now that neurons involved in your Grandma's pie are firing like this, other related information can be spontaneously recalled too. If the neurons stimulate other networks of neurons, you may recall the time you burnt a pie, or the time you dunked for apples at a carnival, or the day your Grandmother died; depending on which neural nets are stimulated by N1, N2, and N3.

Where is the memory in your brain? Distributed over many neurons involved in many networks and encoded within specific possible firing patterns. It's not a "thing" itself, it's just a pattern that things can possess.

When a memory is weakened, the neurons that comprise the set containing the memory may disconnect, though are still capable of reconnecting later, if the proper stimuli promotes it. There is no "force" prompting these neurons to search for each other; the tangential and relational nature of the brain causes them to work together, recalling varied information, simply by acting on the stimuli presented to it.

Memory is not a "thing" (it's not a pattern of connections between objects, but is a relation between a particular set of connected objects, a pattern of connected neurons, that interact in a predetermined "coded" pattern of activity with each other), it is a function of pattern activation, a process. That's why you don't remember all things all the time; simply possessing the patterns of connections between neurons is not enough. They must fire properly to cause the experience of a recalled memory.