Brain's Support Cells Could Explain Mysterious "Spreading Pain" - Scientific American

In people who suffer from pain disorders, painful feelings can severely worsen and spread to other regions of the body. Patients who develop chronic pain after surgery, for example, will often feel it coming from the area surrounding the initial injury and even in some parts of the body far from where it originates. New evidence suggests glia, non-neuronal cells in the brain, may be the culprits behind this effect.

Glia were once thought to simply be passive, supporting cells for neurons. But scientists now know they are involved in everything from metabolism to neurodegeneration. A growing body of evidence points to their key role in pain. In a study published today in Science, researchers at the Medical University of Vienna report that glia are involved in long-term potentiation (LTP), or the strengthening of synapses, in pain pathways in the spinal cord.

Neuroscientists Timothy Bliss and Terje Lømo first described LTP in the hippocampus, a brain area involved in memory, in the 1970s. Since then scientists have been meticulously studying the role this type of synaptic plasticity—the ability of synapses to change in strength—plays in learning and memory. More recently, researchers discovered that LTP could also amplify pain in areas where injuries or inflammation occur. "We sometimes call this a 'memory trace of pain' because the painful insult may lead to subsequent hypersensitivity to painful stimuli, and it was clear that synaptic plasticity can play a role here," says study co-author Jürgen Sandkühler, a neuroscientist also at the Medical University of Vienna. But current models of how LTP works could not explain why discomfort sometimes becomes widespread or experienced in areas a person has never felt it before, he adds.

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https://www.scientificamerican.com/article/brain-rsquo-s-support-cells-could-explain-mysterious-ldquo-spreading-pain-rdquo/

A New Study Tests Marijuana's Potential to Replace Opioid Painkillers - The Atlantic

Emily Lindley's stash of marijuana is going to be very, very secure.

Lindley, a neurobiologist, is about to begin the first study ever to directly compare cannabis with an opioid painkiller (in this case, oxycodone) for treating people with chronic pain. She got a grant for this research two years ago, but it has taken that much time to meet all the requirements for working with a drug the federal government still considers highly dangerous.

Before it's given to patients, the marijuana will be kept inside steel narcotics lockers bolted to the wall in a room with surveillance cameras and a combination keypad on the door. Each locker has tamper-proof hinges and requires two keys—each held by a different person. If someone puts the wrong key in one of the locks, it will become inoperable and have to be drilled out.

All this is necessary to comply with rules imposed by the Drug Enforcement Agency to make sure drugs meant for research don't end up on the street, says Heike Newman, a senior regulatory manager at the University of Colorado's Anschutz Medical Campus, where Lindley's study will take place. Newman's job is to help researchers with the paperwork they need to file with various government agencies to get approval for their studies. She says the lockers and renovations to the storage room cost the university about $15,000.

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http://www.theatlantic.com/health/archive/2016/11/a-new-test-of-pots-potential-to-replace-painkillers/507200/?

Why painkillers sometimes make the pain worse | Science | AAAS

Mark Hutchinson could read the anguish on the participants' faces in seconds. As a graduate student at the University of Adelaide in Australia in the late 1990s, he helped with studies in which people taking methadone to treat opioid addiction tested their pain tolerance by dunking a forearm in ice water. Healthy controls typically managed to stand the cold for roughly a minute. Hutchinson himself, "the young, cocky, Aussie bloke chucking my arm in the water," lasted more than 2 minutes. But the methadone patients averaged only about 15 seconds.

"These aren't wimps. These people are injecting all sorts of crazy crap into their arms. … But they were finding this excruciating," Hutchinson says. "It just fascinated me." The participants were taking enormous doses of narcotics. How could they experience such exaggerated pain?

The experiment was Hutchinson's first encounter with a perplexing phenomenon called opioid-induced hyperalgesia (OIH). At high doses, opioid painkillers actually seem to amplify pain by changing signaling in the central nervous system, making the body generally more sensitive to painful stimuli. "Just imagine if all the diabetic medications, instead of decreasing blood sugar, increased blood sugar," says Jianren Mao, a physician and pain researcher at Massachusetts General Hospital in Boston who has studied hyperalgesia in rodents and people for more than 20 years.

But how prevalent hyperalgesia is, and whether it plays a role in the U.S. epidemic of opioid abuse and overdose, is unclear. A lack of reliable testing methods and a series of contradictory papers have created believers and skeptics. A few researchers, like Mao, think hyperalgesia is an underappreciated puzzle piece in the opioid epidemic—a force that can pile on pain, drive up doses, and make it harder for chronic users to come off their drugs. Some of those researchers are looking for ways to turn down hyperalgesia, to help patients function on lower doses of their oxycodone, for example, or make it easier to taper off it altogether. Others see OIH as an oddity in the literature—real, and a powerful clue to the workings of pain pathways, but unlikely to tighten the grip of opioids on most patients. Hutchinson thinks the majority of physicians are either unaware of hyperalgesia or unconvinced of its importance. "I think if you surveyed prescribers of opioids, they would be divided probably 60–40."

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http://www.sciencemag.org/news/2016/11/why-painkillers-sometimes-make-pain-worse