A chemical in the brain typically associated with cognition, movement and reward-motivation behavior — among others — may also play a role in promoting chronic pain, according to new research at The University of Texas at Dallas.
The chemical, dopamine, sets the stage for many important brain functions, but the mechanisms that cause it to contribute to chronic pain are less well understood.
In a recent paper published in the Journal of Neuroscience, UT Dallas researchers followed the sequence of pain impulses traveling from the brain to the spinal cord in mice. They found that by removing a collection of neurons called A11 that contain dopamine, chronic pain was selectively diminished.
“These findings demonstrate a novel role for how dopamine contributes to maintaining chronic pain states,” said Dr. Ted Price, associate professor in the School of Behavioral and Brain Sciences at UT Dallas. “This may open up new opportunities to target medicines that could reverse chronic pain.”
Pain signals travel like electricity from an injury to the spinal cord where they pass on electrical or chemical pain signals to other cells. Those pain signals then travel upward and relay that information to neurons in the brain where they can be distributed throughout. There is no single pain center in the brain, but there is substantial evidence that chronic pain changes how these pain centers are activated.
In people with chronic pain, neurons continue to send pain signals to the brain, even in the absence of injury, but the causes of this are not known.
A potential explanation comes from A11. These neurons didn’t affect acute pain, but they did have a profound effect on chronic pain, researchers found. By targeting these neurons in mice with chronic pain, the researchers permanently reversed a chronic pain state.
Price said that previous studies have examined the role of other neurotransmitters in chronic pain including norepinephrine and serotonin.
“By process of elimination, we decided to look more closely at dopamine. We used a toxin that affected A11 neurons, and that’s when we found that acute pain signals were still normal, but chronic pain was absent,” he said.
In 2011, the Institute of Medicine estimated that more than 100 million Americans suffer from chronic pain, a condition that costs more than $600 billion each year in medical care and lost productivity.
Understanding the basis of chronic pain and all of its contributing factors could help point to more effective treatments.
“In future studies, we would like to gain a better understanding of how stress interacts with A11,” Price said. “And we’d like to know more about the interaction between molecular mechanisms that promote chronic pain and dopamine.”
The study was led by Dr. Ji-Young Kim, a recent PhD graduate of Price’s laboratory. Other UT Dallas researchers included Galo Mejia, a research assistant, and Dr. Greg Dussor, associate professor. Researchers from the University of Arizona and the University of Alabama at Birmingham also contributed.
Funding: The study was funded in part by The University of Texas at Dallas, the National Institutes of Health and the Rita Allen Foundation.
Source: Katherine Morales – UT Dallas
Image Source: The image is credited to Jynto and is in the public domain
Original Research: Abstract for “Spinal Dopaminergic Projections Control the Transition to Pathological Pain Plasticity via a D1/D5-Mediated Mechanism” by Ji-Young V. Kim, Dipti V. Tillu, Tammie L. Quinn, Galo L. Mejia, Adia Shy, Marina N.K. Asiedu, Elaine Murad, Alan P. Schumann, Stacie K. Totsch, Robert E. Sorge, Patrick W. Mantyh, Gregory Dussor, and Theodore J. Price in Journal of Neuroscience. Published online April 22 2015 doi:10.1523/JNEUROSCI.3481-14.2015
Abstract
Spinal Dopaminergic Projections Control the Transition to Pathological Pain Plasticity via a D1/D5-Mediated Mechanism
The mechanisms that lead to the maintenance of chronic pain states are poorly understood, but their elucidation could lead to new insights into how pain becomes chronic and how it can potentially be reversed. We investigated the role of spinal dorsal horn neurons and descending circuitry in plasticity mediating a transition to pathological pain plasticity suggesting the presence of a chronic pain state using hyperalgesic priming. We found that when dorsal horn neurokinin 1 receptor-positive neurons or descending serotonergic neurons were ablated before hyperalgesic priming, IL-6- and carrageenan-induced mechanical hypersensitivity was impaired, and subsequent prostaglandin E2 (PGE2) response was blunted. However, when these neurons were lesioned after the induction of priming, they had no effect on the PGE2 response, reflecting differential mechanisms driving plasticity in a primed state. In stark contrast, animals with a spinally applied dopaminergic lesion showed intact IL-6- and carrageenan-induced mechanical hypersensitivity, but the subsequent PGE2 injection failed to cause mechanical hypersensitivity. Moreover, ablating spinally projecting dopaminergic neurons after the resolution of the IL-6- or carrageenan-induced response also reversed the maintenance of priming as assessed through mechanical hypersensitivity and the mouse grimace scale. Pharmacological antagonism of spinal dopamine D1/D5 receptors reversed priming, whereas D1/D5 agonists induced mechanical hypersensitivity exclusively in primed mice. Strikingly, engagement of D1/D5 coupled with anisomycin in primed animals reversed a chronic pain state, consistent with reconsolidation-like effects in the spinal dorsal horn. These findings demonstrate a novel role for descending dopaminergic neurons in the maintenance of pathological pain plasticity.
“Spinal Dopaminergic Projections Control the Transition to Pathological Pain Plasticity via a D1/D5-Mediated Mechanism” by Ji-Young V. Kim, Dipti V. Tillu, Tammie L. Quinn, Galo L. Mejia, Adia Shy, Marina N.K. Asiedu, Elaine Murad, Alan P. Schumann, Stacie K. Totsch, Robert E. Sorge, Patrick W. Mantyh, Gregory Dussor, and Theodore J. Price in Journal of Neuroscience. Published online April 22 2015 doi:10.1523/JNEUROSCI.3481-14.2015
