Researchers Flip Perception on Bladder Pain, Brain Lateralization
Neuroscientists have known since the 19th century that corresponding regions of the left and right hemispheres of the brain don’t always perform the same functions. Imaging studies have more recently documented this lateralization in the context of chronic pain, specifically in the amygdala, where emotional processing also occurs.
A team of researchers led by Dr. Benedict Kolber, associate professor of neuroscience in the School of Behavioral and Brain Sciences at The University of Texas at Dallas, has demonstrated in mice that a single neuropeptide has opposite effects on chronic bladder pain when the molecule is active in matching regions of opposite hemispheres of the brain. The research was published in the Feb. 15 print issue of the journal Biological Psychiatry.
“This finding is particularly striking — it’s flip sides of the same coin,” said Kolber, who is corresponding author of the study and is affiliated with the Center for Advanced Pain Studies at UTD. “It’s bizarre. It speaks to the flexibility of natural systems. While in many cases there’s redundancy, there can also be specialization that evolves.”
Kolber’s team conducted its study on a mouse model of bladder pain. When the researchers introduced the protein calcitonin gene-related peptide (CGRP) to the animals’ amygdalae, they found that CGRP administered in the right side increased behavioral signs of bladder pain, but when administered in the left side, it decreased painlike behavior in the bladder.
“There are other examples in the amygdala of situations in which one side has a specialized receptor that increases pain, and the other side doesn’t do anything. But none with counteractive effects like this,” Kolber said. “CGRP is driving pain on the right side and reducing pain on the left.”
Lead author Dr. Heather Allen, a UT Dallas visiting scholar and a postdoctoral associate at New York University, said that lateralization is often ignored in pain research.
“This finding is particularly striking — it’s flip sides of the same coin. It’s bizarre. It speaks to the flexibility of natural systems. While in many cases there’s redundancy, there can also be specialization that evolves.”Dr. Benedict Kolber, associate professor of neuroscience in the School of Behavioral and Brain Sciences
“Here, we demonstrate that bladder pain — visceral pain in a centrally located organ — is processed differently on the left and right sides of the brain,” she said. “If we had focused on only one side of the amygdala, we would have completely missed out on discovering these divergent functions.”
Kolber’s area of expertise is urologic chronic pelvic pain syndrome, an umbrella term for varieties of pain that affect an estimated 10 million people in the U.S. each year, primarily middle-aged women.
“It’s a huge area of clinical need, and we don’t know how to treat it,” he said. “So while this is a broader story about lateralization, we’re also seeking specific answers. The patient is the priority — I want to understand this disease so it can be treated in humans.”
Kolber said there have probably been hundreds of studies that went unpublished by researchers who moved on because they assumed there was no difference between hemispheres. He said his group’s results could enable progress in research on other medical conditions, including stroke, depression, and some learning and memory phenomena.
“We’re discovering something about nature, something fundamental. That’s really exciting,” he said.
Allen said the next step is to identify the reason for the polar opposite behavior on matching sides of the brain in response to the same neuropeptide.
“We are currently investigating the signaling pathway from CGRP-positive cells in the amygdala to other parts of the brain to see if that provides any evidence,” she said. “We are also investigating these findings in other pain models to evaluate if this phenomenon is isolated to bladder pain or whether it extends to other types of pain.
“Chronic pain treatments are often ineffective largely because we still don’t truly understand the underlying mechanisms. Understanding these pain pathways will hopefully help us design effective therapeutics in the future.”
Additional contributors to the research include UT Dallas neuroscience research associate Dr. Lakeisha Lewter, and cognition and neuroscience doctoral student Veronica Hong, as well as researchers from the University of Pittsburgh and the National Center for Complementary and Integrative Health of the National Institutes of Health (NIH).
The work was supported by three NIH grants (F31DK121484, R01DK115478 and F32DK128969).
Original source can be found here
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