Drug allows morphine to relieve pain without addiction - health - 14 August 2012 - New Scientist

A potential new treatment to prevent morphine addiction is at hand. Researchers have identified an immune receptor involved in addiction to the drug, and found a way to block this receptor without affecting pain relief. The discovery offers hope that morphine can be used to relieve pain without running the risk of addiction.

Opioid drugs such as morphine are known to target opioid receptors in the central nervous system, which block pain signals to the brain and flood it with the "feel-good" chemical dopamine. This reward response is what makes opioids so addictive.

Morphine is a widely used pain killer, but its addictiveness means it has to beadministered with caution, and often cannot be used for protracted periods of chronic pain.

Mark Hutchinson from the University of Adelaide, Australia, and colleagues have now discovered that as well as working through the central nervous system, opioid drugs like heroin and morphine trigger an immune response, which seems to boost their addictive effects. Blocking this immune response in animals inhibits their addiction.

Hutchinson's team previously observed that opioids bind to TLR-4 – immune system receptors in the cell membrane – which are responsible for identifying foreign bodies. However, the team did not know how this binding affected the body.

Immunity receptor block

In their latest study, the team found that the receptor acts as an amplifier of reward when opioids are bound to it. The team did a series of experiments looking at addictive behaviour in rats and mice that had been given either morphine alone, or a drug called plus-naloxone – which blocks the TLR-4 receptor – followed by morphine.

Rats given plus-naloxone before receiving morphine did not exhibit behaviour linked to addiction. Their brains also showed a significantly lower release of dopamine than in rats that only received morphine. Using a heat sensitivity test, the team also showed that the rodents given plus-naloxone still experienced pain relief from the morphine, despite lacking signs of addiction.

To make sure that the TLR-4 receptor really was controlling these differences, the team also bred rats that lacked the receptor. Under the same tests, these rats behaved like those that had been given plus-naloxone.

The idea that the rewarding effect of opioid drugs is potentially mediated by this receptor "flies in the face of current opinion," says Chris Bailey, a pharmacologist from the University of Bath in the UK. "People for hundreds of years have been trying to come up with an opioid analgesic which isn't rewarding," he says.

These findings are particularly interesting, he says, because it's the first time a mechanism has been identified that separates the pain relief and reward responses to opioid drugs. "It has always been seen that the analgesia and the rewarding aspects go hand in hand," he says.

The next step will be to find out exactly how the receptor helps to control the reward behaviours linked to addiction, he adds. Clinical trials to test the effectiveness of combining morphine with a drug like plus-naloxone could begin as soon as 18 months from now.

Journal reference: Journal of Neuroscience, DOI: 10.1523/jneurosci.0684-12.2012

http://www.newscientist.com/article/dn22176-drug-allows-morphine-to-relieve-pain-without-addiction.html

Why Do Women Get More Migraines? - ScienceNOW

Migraines are a battle of the sexes that women might prefer not winning. Each year, roughly three times more women than men—up to 18% of all women—suffer from the debilitating headaches, as tallied by epidemiological surveys in Europe and the United States. A new brain imaging study may explain the divide: The brains of women with migraines appear to be built differently than those of their male counterparts.

To conduct the study, researchers headed by David Borsook, a neurologist and neurobiologist of Boston Children's Hospital and Harvard Medical School, recruited 44 men and women, half of whom were migraine sufferers. The women who had migraines rated them as being as intense as the men did, but they tended to find them more unpleasant. Borsook says the distinction is analogous to the loudness of fingernails scratching on a chalkboard versus the torment of hearing the sound.

The team then scanned the brains of the volunteers. The researchers gathered two kinds of data sets, one that captured brain shapes and features, and one that measured brain activity. Female migraine sufferers showed slightly thicker gray matter in two regions: one, the posterior insula, is well-known in pain processing; the other, the precuneus, has been recently linked to migraines but is more widely known as a fundamental brain hub that may house a person's consciousness or sense of self. The other volunteers, including the male migraine sufferers, did not show this thickening. All of the scans were done when people did not have a migraine.

To figure out what those structural changes meant, lead author Nasim Maleki, a medical physicist at Boston Children's Hospital and Harvard Medical School, returned to the MRI scans of only those men and women with episodic migraines. The team compared brain activity while the volunteers experienced pain—in this case, three 15-second bursts of heat to the hand, spaced 30 seconds apart, generated through a small metal cube, akin to touching a too-hot cup of coffee. In women with migraines, "these thicker areas talk to each other and work together to respond to pain" in a pattern not seen in the men, Maleki says.

When Maleki checked for sex differences in well-defined pain networks, most of the structures that responded stronger in women were part of the emotional network. "In men, the pain comes in, and the brain says 'ouch,' " Maleki says. "In women, the brain says 'OUCHHHHH!' " Overall, the results suggest that "it's not just one area that underlies the sex differences in migraines, but a network of areas, a system that leads to the problem or progression," she says.

In only men, those with migraines had a stronger reaction to the heat pain in a specific area—the nucleus accumbens—that is part of the reward circuitry and is extensively studied in the addiction research, Maleki says. "Interestingly, as much as pain syndromes are more prevalent in women and disproportionate relative to men, in addiction it is the opposite," she says. "Men are more likely to develop addictions, and the prevalence is higher in men. So, is the reward circuitry somehow involved in migraine pathophysiology in men? Are there overlaps between pain pathways and reward pathways? The answer is that we don't know. But I think these results just help us ask more targeted questions in understanding how migraine works." The study is published this month in the journal Brain.

The findings reveal a clearly different brain pattern that may explain why so many more women than men have migraines, says neurologist Peter Goadsby of the University of California, San Francisco, who was not involved in the study. "Migraines have traditionally not been appreciated as a significant brain disorder," adds Andrew Charles, a neurologist at the University of California, Los Angeles. "Studies like this take migraines out of the realm of the subjective and show fundamental brain changes responsible for these differences. It's quite validating for people with migraines who understand something quite significant is happening in their heads."

Most interesting to Andrew Ahn, a neuroscientist at the University of Florida College of Medicine in Gainesville, are the findings that emphasize the emotional processing of pain. "Pain is an experience, a product of processing by the brain of a stimulus plus the way your brain interprets that stimulus," he says. "It's exciting that the pain field has come to recognize changes that occur in brains of people with chronic pain."

The greater activation of emotional pain processing regions in women "could correlate with the greater sense of unpleasantness that is experienced by women with migraine and the higher prevalence of depression and anxiety in women with migraine," speculates Todd Schwedt, a neurologist at the Mayo Clinic in Phoenix.

For Schwedt and others, the study provokes many new questions. Are the brain differences a cause or effect of migraines? Are they permanent or transient? And are they a response to pain in general or migraines in particular?

The study also highlights therapeutic issues for both men and women. Even with the best medical management, medication reportedly works in about only half of all people and then in about only half of all migraine attacks. More attention may need to be paid to gender in research, Maleki says. Most of the animal studies have involved male rodents, she says, and women are disproportionately represented in clinical studies by an 8:1 margin.

Still, Goadsby cautions that there are no immediate clinical implications. "It's fair to say that these are subtle changes in a research study and not ones that we would expect to see in ordinary imaging," he says. "There is no reason to go out and have your brain imaged."

http://news.sciencemag.org/sciencenow/2012/08/why-do-women-get-more-migraines.html?ref=hp

Good news: Migraines hurt your head but not your brain - Medical Xpress

Migraines currently affect about 20 percent of the female population, and while these headaches are common, there are many unanswered questions surrounding this complex disease. Previous studies have linked this disorder to an increased risk of stroke and structural brain lesions, but it has remained unclear whether migraines had other negative consequences such as dementia or cognitive decline. According to new research from Brigham and Women's Hospital (BWH), migraines are not associated with cognitive decline.

This study is published online by the British Medical Journal (BMJ) on August 8, 2012. "Previous studies on migraines and cognitive decline were small and unable to identify a link between the two. Our study was large enough to draw the conclusion that migraines, while painful, are not strongly linked to cognitive decline," explained Pamela Rist ScD, a research fellow in the Division of Preventive Medicine at BWH, and lead author on this study.

The research team analyzed data from the Women's Health Study, a cohort of nearly 40,000 women, 45 years and older. In this study, researchers analyzed data from 6,349 women who provided information about migraine status at baseline and then participated in cognitive testing during follow-up. Participants were classified into four groups: no history of migraine, migraine with aura (transient neurology symptoms mostly of the visual field), migraine without aura, and past history of migraine. Cognitive testing was carried out in two year intervals up to three times.

"Compared with women with no history of migraine, those who experienced migraine with or without aura did not have significantly different rates of cognitive decline," explained Rist. "This is an important finding for both physicians and patients. Patients with migraine and their treating doctors should be reassured that migraine may not have long term consequences on cognitive function."

There is still a lot that is unknown about migraines. However this study offers promising evidence for patients and their treating physicians. More research needs to be done to understand the consequences of migraine on the brain and to establish strategies to influence the course of the disease in order to optimize treatment strategies

http://medicalxpress.com/news/2012-08-good-news-migraines-brain.html