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RESEARCH BRIEFSPain and Pleasure Activate Same Brain StructuresThe notion of a fine line between pain and pleasure is finding support in biology, according to a new report by Massachusetts General Hospital researchers. David Borsook and his colleagues have discovered that circuits in the brain that are responsible for reacting to pleasurable experiences also respond to painful ones.
The same areas of the brain (highlighted above) respond to both painful and pleasurable stimuli. Images courtesy of David Borsook Even more surprising, some of the circuits associated with reward appear to react more quickly to hurtful stimuli than do the sensory areas of the brain traditionally associated with pain. The findings appear in the Dec. 6 Neuron. The idea for the study arose in part out of Borsook's experience as a clinician. "Over 15 years of seeing patients with pain it became obvious that we do not have good methods of assessing chronic pain," said Borsook, HMS associate professor of radiology. "And we do not have good methods for treating it." To get a better understanding of the actual neuronal circuits involved in pain, Borsook; Lino Becerra, HMS assistant professor of radiology; and their colleagues attached thermodes, which deliver either warm or painfully hot temperatures for 25 seconds, to the hands of eight male volunteers. They imaged the brains of each subject as he was exposed to the stimuli. The painful hot temperatures activated not only the classic pain circuitry but also structures previously identified as being activated in response to emotionally rewarding stimuli, such as cocaine, food, and money. The emotional circuits became most active immediately after heat exposure, while the sensory areas showed their greatest burst of activity later in the 25-second interval. "It's the first time we have seen something aversive activating these reward structures," said Becerra. One explanation is that these areas are simply responding to salient stimuli. Gaining a better grasp on the pain circuitry in the brain could lead to new treatments. "Prior to our study, most data could define the sensory response," he said. "Understanding this newly identified emotional component may be a key to developing new approaches to helping chronic pain patients, who are at increased risk for anxiety, depression, and suicide."
Microbial Master of Disguise Is UnmaskedThe intestine is home to thousands of microorganisms, each having to protect itself not just against the immune system but also from competitive onslaughts by its microbial neighbors. A team of HMS researchers is gaining insight into how at least one bacterial species manages to elude its would-be predators. The bug appears to be a master of disguise. It achieves its mastery by manufacturing eight capsular polysaccharides, which is more than any other species has been found to make. What is more, the wily Bacteroides fragilis appears to have the ability to turn on the synthesis of each of these polysaccharides independently, for a total of 256 possible combinations. Laurie Comstock, Corinna Krinos, Dennis Kasper, and their colleagues at Brigham and Women's Hospital report in the Nov. 29 Nature that the promoter for the synthesis of each polysaccharide operon consists of a piece of DNA that can flip itself in either of two directions. "In one orientation, it does not transcribe the gene; in the other it does," said Comstock, HMS assistant professor of medicine. Each of the promoters flips independently, giving the microbe a huge inventory of possible disguises. The question of how B. fragilis outwits its intestinal competitors was not on the mind of Comstock; Krinos, a researcher in medicine; Kasper, the William Ellery Channing professor of medicine and executive dean for academic programs at HMS; and their colleagues when they embarked on the study. Though B. fragilis makes its home in the intestine, during surgery it may leak into the abdominal cavity, where it can cause dangerous abscesses to form. The researchers wanted to know how it did that. They knew the microbe made four capsular polysaccharides, which they cloned. Curiously, each of the four loci began with the same two genes. Using genomic data from the Sanger Center, they scoured the B. fragilis genome for other areas that began with the two genes and turned up four additional loci, for a total of eight. Further work revealed that the genes did in fact encode products involved in the synthesis of polysaccharides. The polysaccharides have been identified, but there is still the more difficult question of how the microbe uses them. "Commensalism is much more difficult to study," said Comstock. " You have to take into account not only the host but all the other organisms living there." --Misia Landau
Risk of Mad Cow Disease in U.S. Called LowAmericans may dig into their Christmas roast beef with more gusto--or at least, less worry--after hearing results of a new report from HSPH's Harvard Center for Risk Analysis. The study was done by HCRA scientists for the U.S. Department of Agriculture, and it offers the first detailed statistical projections of the risk of "mad cow disease" to the bovine and human populations in the country if infected animals were to enter American cattle herds. The disease, more accurately known as bovine spongiform encephalopathy (BSE), has not been reported in the U.S., and cattle imports from the United Kingdom, the site of the worst outbreak, have been banned since 1989. In humans, eating BSE-tainted meat can cause variant Creutzfeldt-Jacob disease, a fatal neurological disorder. But the study suggests that such risks are likely to be very low under any plausible circumstances. A team of researchers, led by HCRA acting director George Gray, studied the disease and its origins in the U.K. and other European countries and the level of American compliance with government regulations designed to reduce BSE risk. Then, senior research associate Joshua Cohen and research associate Silvia Kreindel of the center, along with MIT doctoral student Keith Duggard, constructed a computer model to simulate the course of the disease under several dozen scenarios involving the introduction of one to 500 BSE-infected animals to the U.S. herd. Even under the worst-case scenarios, they estimate that the number of subsequently infected animals would remain small, the outbreak would die out within a few years, and the amount of contaminated meat entering the human food supply would be minimal.
Animal Model for Obesity DevelopedThe best predictor of the common health consequences of obesity--including diabetes and unhealthy blood lipid levels--is not the total amount of body fat but the quantity of visceral fat surrounding the organs deep in the abdomen. The precise molecular mechanisms underlying visceral fat accumulation are unknown, but a leading suspect is 11-beta hydroxysteroid dehydrogenase type 1 (11-beta HSD-1). This enzyme raises intracellular levels of metabolically active glucocorticoid hormones (cortisol in humans) by regenerating them from inactive forms. Excess amounts have been implicated in visceral obesity. Researchers from HMS, along with collaborators from the University of Edinburgh, Scotland, have created a transgenic mouse model that mimics the overexpression of the gene for 11-beta HSD-1, seen in adipose tissue of obese people, and lends support to the connection between 11-beta HSD-1 and the "metabolic syndrome" of insulin resistance and hyperlipidemia. Senior author Jeffrey Flier, the George C. Reisman professor of medicine at Beth Israel Deaconess Medical Center, and first author Hiroaki Masazuki, a visiting scientist, led the study, which appears in the Dec. 7 Science. They introduced a rat version of the 11-beta HSD-1 gene into the mice under the control of a promoter gene that induces 11-beta HSD-1 expression selectively in adipose tissue. Levels of corticosterone (the rodent equivalent of cortisol) were similar in the serum of the transgenic mice and control animals, but were increased by 15 to 30 percent in the adipose tissues of the transgenics. The transgenics ate 10 to 17 percent more food than controls, and by 15 weeks of age, their weight averaged 16 percent higher. "These findings strongly suggest that increased adipocyte 11-beta HSD-1 is a common molecular mechanism for visceral obesity and the metabolic syndrome and may be an exciting pharmaceutical target for the treatment of this prevalent disorder," the authors write. --Tom Reynolds |
