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

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McGill researchers test a rat's pain threshold

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.

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Gary Stix About the Author: Gary Stix, a senior editor, commissions, writes, and edits features, news articles and Web blogs for SCIENTIFIC AMERICAN. His area of coverage is neuroscience. He also has frequently been the issue or section editor for special issues or reports on topics ranging from nanotechnology to obesity. He has worked for more than 20 years at SCIENTIFIC AMERICAN, following three years as a science journalist at IEEE Spectrum, the flagship publication for the Institute of Electrical and Electronics Engineers. He has an undergraduate degree in journalism from New York University. With his wife, Miriam Lacob, he wrote a general primer on technology called Who Gives a Gigabyte? Follow on Twitter @@gstix1.

The views expressed are those of the author and are not necessarily those of Scientific American.

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  1. 1. TobyNSaunders 11:44 am 02/18/2012

    Maybe one day aliens from another planet will test the pain threshold of humans in order to develop a drug.

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  2. 2. drafter 12:25 pm 02/18/2012

    Interesting concept What if we could get a few habitual criminals with life sentences to volunteer to have their entire memory wiped, re-educated and then released back into society. Not only would it be a great scifi book but maybe an actual method of changing how we deal with criminals. If it were ever tried they would have to be released where no one no them and have a new identity.

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  3. 3. N a g n o s t i c 12:11 pm 02/19/2012

    TobyNSaunders, more likely is one day aliens will find humanity so softened, feminized and impotent due to being overrun by sensitive, squeamish types such as yourself that no effort need be applied in order to take complete control.
    Afterwards, they’ll do whatever they like.

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  4. 4. N a g n o s t i c 12:23 pm 02/19/2012

    Drafter, you’re only describing a form of execution. Once a person’s memories are erased, that person no longer exists. You must know that re-educating the memoryless being resulting from your form of execution will be vastly expensive, not to mention the legal complications resulting from maintaining a population of physically mature, yet mentally child-like humans.

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