University of Michigan researchers used electricity on regions in the brain of a patient suffering chronic and severe facial pain to release an opiate-like substance that may be one of the human body's most powerful painkillers. This expands on research conducted at the University of Michigan, Harvard University and the City University of New York. Researchers delivered electricity through sensors attached to the skulls of patients suffering chronic migraine headaches, finding a decrease in the intensity and pain of their headache attacks. However, researchers are still mystifed about the relief the patients attested.
Alexandre DaSilva, the senior researcher in the study, contends that the current findings help explain what happens in the brain that decreases pain during the brief sessions of electricity. DaSilva, a researcher from the University of Michigan School of Dentistry, was joined in the study by Marcos DosSantos, and also Dr. Jon-Kar Zubieta from the Molecular and Behavioral Neuroscience Institute.
The figure above shows the brain of a chronic pain patient before and during electrical stimulation to induce pain relief. Those areas in red represent the relative number of free mu-opioid receptors, the main target of pharmaceutical opiates. Researchers discovered a decrease in availability of those receptors during electrical stimulation. The results indicate for the first time the active release of local mu-opioid, a powerful substance in the brain that, when binds to the receptor, changes pain perception.
DaSilva and colleagues intravenously administered a radiotracer that reached important brain areas in a patient with trigeminal neuropathic pain (TNP), a type of chronic, severe facial pain. Electrodes were applied to the skull of each patient and electrically stimulated right above the motor cortex of the patient for 20 minutes during a PET scan (positron emission tomography). The stimulation is called transcranial direct current stimulation (tDCS).
The radiotracer was specifically designed to measure, indirectly, the local brain release of mu-opioid. The latter is a natural substance that alters pain perception. For this opiate to function, it needs to bind to the mu-opioid receptor (the study assessed levels of this receptor).
"This is arguably the main resource in the brain to reduce pain," DaSilva said. "We're stimulating the release of our (body's) own resources to provide analgesia. Instead of giving more pharmaceutical opiates, we are directly targeting and activating the same areas in the brain on which they work. (Therefore), we can increase the power of this pain-killing effect and even decrease the use of opiates in general, and consequently avoid their side effects, including addiction." DaSilva said, most pharmaceutical opiates, especially morphine, target the mu-opioid receptors in the brain.
The dose of electricity is infinitesimal. Electroconvulsive therapy (ECT), or 'shock therapy', which is used to treat depression and other psychiatric conditions, uses amperage in the brain ranging from 200 to 1600 milliamperes (mA). The tDCS protocol used in DaSilva's study delivered only 2 mA.
Researchers found that in one session, the patient's threshold for cold pain was improved by 36 percent, but not the patient's clinical, TNP/facial pain. To DaSilva, this suggests that repetitive electrical stimulation over several sessions are required to have a lasting effect on clinical pain as shown in their previous migraine study.
The researchers will now look into the long-term effects of electric stimulation on the brain and find specific targets in the brain that may be more effective depending on the pain condition and patients' status. For example, the frontal areas may be more helpful for chronic pain patients with depression symptoms.
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