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Brain releases powerful, opiate-like painkiller in repsonse to electric stimulation

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January 5, 2013

Electric stimulation of the brain through the skull has been found to release a powerful, ...

Electric stimulation of the brain through the skull has been found to release a powerful, opiate-like painkiller (Image: Shutterstock)

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Twenty to thirty percent of the world's population suffers from some sort of chronic pain, which is far more difficult to control than, say, the pain of a cut or bruise. A great deal of effort has gone into the search for medically acceptable ways to control such pain, with few good answers emerging. Now medical researchers at the University of Michigan have directly demonstrated that transcranial electrical stimulation of a patient's brain causes the release of a natural opiate that dulls or eliminates the perception of pain.

Transcutaneous electric nerve stimulation (TENS) has been used far back into history to relieve chronic pain, with limited success. More recently, however, transcutaneous direct current stimulation (tDCS) has become an accepted, if experimental, method of producing changes in brain function, with multiple applications in treatment of chronic pain. Requiring little more than a nine-volt battery and a pair of electrodes, it involves passing about 1-2 mA of current through the skull and the underlying brain tissue. One of the most important aspects of tDCS is its ability to maintain cortical changes even after the stimulation is ended.

tDCS has been found to speed recovery of stroke patients, help lift a depressed mood, improve memory, speed up training of military snipers, and even improve one's ability to do mathematics. Prior studies by the Michigan group demonstrated that tDCS can decrease the intensity and pain of chronic migraine patients. However, the mechanism was not completely understood at that time.

There are two main classes of chronic pain: chronic pain due to a physical cause, and chronic pain due to nerve damage. Both types can become entrenched physically into the nervous system and brain through neuroplasticity. Roughly speaking, the brain gets into the habit of perceiving pain, and with practice becomes quite skilled at feeling a wide range of sensory inputs as pain. Chronic pain can result from numerous conditions, including arthritis, spinal stenosis, cancer, fibromyalgia, migraine headaches, trigeminal neuralgia, and nerve damage, among many others. In some cases, nothing is clinically observed save for the pain itself.

In the new Michigan study, positron emission tomography (PET) antibody studies showed that tDCS stimulation of the motor cortex causes the active release of an opiate-like substance (beta-endorphin) considered to be one of the body's most powerful painkillers. The tDCS unit was set to supply two mA of current, with electrons being introduced into the primary motor cortex and removed through the forehead.

The patient suffered from intense chronic pain from trigeminal neuralgia, a disease of the trigeminal nerve that produces episodes of such intense pain that it has been called the "suicide" disease. One 20 minute tDCS treatment significantly reduced the patient's pain reaction to a cold stimulus, but relief of the chronic pain required multiple treatments. This suggests a distinction between acute and chronic pain, wherein chronic pain becomes habitual to the brain through neuroplastic strengthening of the pain perception circuits. This observation helps to explain why chronic pain is so difficult to treat.

PET scan of a patient's brain before and after tDCS stimulation with red and yellow showin...

The PET scans above show the brain of a chronic pain patient before and during electrical stimulation to induce pain relief. The areas in red represent the relative number of free mu-opioid receptors, the main target of pharmaceutical opiates. They found a decrease in availability of those receptors following electrical stimulation. The results indicate for the first time the active release of endogenous mu-opioid agonists in response to tDCS treatment.

"This is arguably the main resource in the brain to reduce pain," said Prof. DaSilva, one of the lead researchers. "We're stimulating the release of our (body's) own resources to provide analgesia."

Next, researchers will investigate long-term effects of electric stimulation on the brain and find specific targets in the brain that may be more effective for particular pain conditions.

The team's study appears in the journal Frontiers in Psychiatry.

Source: University of Michigan

About the Author
Brian Dodson From an early age Brian wanted to become a scientist. He did, earning a Ph.D. in physics and embarking on an R&D career which has recently broken the 40th anniversary. What he didn't expect was that along the way he would become a patent agent, a rocket scientist, a gourmet cook, a biotech entrepreneur, an opera tenor and a science writer.   All articles by Brian Dodson
9 Comments

Exciting research to reduce drugs in the treatment of pain. It's not something you hear much about outside medical journals - good work Brian.

Australian
6th January, 2013 @ 02:11 pm PST

If the pain that needs to be relieved is strong the endogenous opiate might get depleted and end up feeling like 'suicide tuesday' after esctasy use. Long term use might create dependence (you will not release any opiate if not externally stimulated). But it's a good research anyway!

And Brian, great, great article. My suggestions were heard! :)

cachurro
6th January, 2013 @ 06:30 pm PST

To the SciFi community, this would be known as wire-heading. And likely just as addictive as any painkiller can be. Good article.

Hoyt Mcguyer
7th January, 2013 @ 09:53 am PST

Well, a less disruptive, but actually little-understood pain treatment option is 'Electric Acupuncture', where a eastern theraphist inserts needles into various acupuncture points on your body and passes a low voltage electric current through the needles. Apparently this re-aligns your Chi or nervous energy flow within your body so that debilitating pain is somehow greatly reduced, but they don't really understand the how and why of this medical option.

Techrex
7th January, 2013 @ 12:32 pm PST

Wonderful. Another attempt to conduct research directed at ridding people of pain. The article makes it clear that such research, of course, is being conducted properly, with our implicit goals clearly in mind. At no time is "pleasure" the goal. God forbid. We must find a drug that removes pain, without allowing for the tiniest pleasure, which would be a sin. No reputable scientist would permit pleasure to sully and contaminate his research. Reputalble scientists are smart enough to understand, that allowing pleasure to intrude on proper research has no place in "good" science, and the pursuit of pleasure is just a liberal conspiracy to make us all happy, a goal completely at odds with God's plan.

Sarcasm aside, I believe that what we call pleasure, is the proper functioning of our body, as it exists at its earliest points, at the earliest ages, when contaminated air, "baby food," candy, an environment filled with toxins, insecticides, pesticides, abnormal stresses, etc., have not yet destroyed the small child's natureal energy, pleasure and exhuberance. Most recreational, casual, drug use, which includes alcohol and marijuana, is almost always an effort by young people, to re-establish the lost happiness, a happiness they can never forget as it is ingrained in their memory, in their cells, and, that came so naturally to them. These efforts are never wholly successful, and nearly always come with risks, sometimes dangerous risks.

JOHN POLIFRONIO
8th January, 2013 @ 05:33 pm PST

I had some really bad pain in my shoulder that was not treatable.I got shocked working on a soft ice cream machine and the pain went away,that was 10 years ago.Who knows.

Ernest Garee
8th March, 2013 @ 09:25 am PST

Just proofreading that headline makes me want brain stimulation.

hologram
9th March, 2013 @ 11:01 am PST

Still some time before Philip K Dick's "Mood Organ" happens.

Seth Miesters
10th August, 2013 @ 09:44 am PDT

ENDOGENOUS MORPHINE

beta endorphin is understood as one endogenous peptide (composed of amino acids) that is closest to morphine in some cellular activity.

recently however an amazing line of research seems to be closing in on empirical status, regarding morphine the alkaloid, formally known as only occuring in the opium poppy, that has been found to be a natural component of biosynthesis.

yes, morphine occurs naturally in humans, other animals, including some amphibians, invertebrates.

white blood cells are gene encoded to produce morphine in the blood stream in an apparent reaction to sepsis,

and, in the brain, morphine is produced intracellulary for what reasons are not so clear yet, but I will reckon to guess that morphine is far more important to cognition and behavior than was formally thought as just a treatment for pain, and as an addictive agent.

recent research seems to suggest, that with some disparate type of compounds such as nicotine, ethanol (consumable alcohol and also an endogenous compound)and cocaine, that habituation to such compounds is enforced via the resulting endogenous production of morphine in the brain.

I assume that other compounds, and activities probably reinforce the natural endogenous production of morphine, such as fasting, exercise, sexercise, and maybe many other actions.

the biosynthesis of morphine in humans seems to follow the opium poppies same production pathway, L-tyrosine, the same amino acid that is used to produce dopamine, is required to produce morphine in the body, but instead of one molecule as with dopamine, morphine requires two molecules of L-tyrosine.

reticuline is a compound that occurs in the process, which is a compound that is found both in our food supply in a USDA approved fruit, and also in various medicinal plants, one of which was recently approved by the FDA, rewardeding a company with a patent for such use of the plant that falls in line with proven medical claims.

the line of intermediates is somewhat complicated, reticuline is transformed into a variety of compounds that follows to thebaine, the precursor also for oxycontin (which seems to be a natural compound found in one species of orchid) and is then turned into codeine, and then finally to morphine.

some people lack proper enzyme levels to process codeine to morphine, in those people thebaine may actually be toxic, and people that are allergic to codeine, may well want to stay away from reticuline containing sources of food.

as morphine has been found in beef brain, I reckon that some meat products may contain precursors to morphine or morphine itself, although it seems that most of the activity of endogenous morphine takes place within the brain, and the BBB probably insulates the bloodstream from distributing the compound elsewhere in the body, and as such, normally wont show up in urine or blood tests, but only in cases where forensics test actual brain matter.

back in the mid century, parkinson disease researchers found that LDOPA supplementation was somehow producing morphine in the urine of inpatient clinical test patients.

why it took so long for a compound such as morphine to be found to be an endogenous component is anyones guess I imagine....a recent paper centering on the behavioral health aspects of this finding paints a disturbing picture.

that electrical stimulation may have some interaction or beneficial use with endogenous morphine is an interesting question for sure.

opiohaus
18th January, 2014 @ 08:14 pm PST
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