Researchers identify brain circuitry in rodents that may be responsible
for negative emotional aspects of pain

Date:
October 18, 2021
Source:
NIH/National Institute on Drug Abuse
Summary:
A new study has uncovered neuronal circuitry in the brain of
rodents that may play an important role in mediating pain-induced
anhedonia -- a decrease in motivation to perform reward-driven
behaviors. Researchers were able to change the activity of this
circuit and restore levels of motivation in a pre-clinical model
of pain tested in rodents.



FULL STORY ==========================================================================
A new study published today in Nature Neurosciencehas uncovered neuronal circuitry in the brain of rodents that may play an important role in
mediating pain-induced anhedonia -- a decrease in motivation to perform reward-driven behaviors. In the study funded by the National Institute on
Drug Abuse (NIDA), part of the National Institutes of Health, researchers
were able to change the activity of this circuit and restore levels of motivation in a pre-clinical model of pain tested in rodents.


==========================================================================
On a basic level, pain includes two components -- sensory (the pain
you feel) and affective (the negative emotional component of pain). The presence of anhedonia, a hallmark of affective pain, is a common feature
of depression, and may also increase one's vulnerability to opioid use
disorder (OUD). Given this relationship, better understanding the brain circuitry involved in the affective component of pain is an important
part of NIDA's research portfolio.

"Chronic pain is experienced on many levels beyond just the physical, and
this research demonstrates the biological basis of affective pain. It is a powerful reminder that psychological phenomena such as affective pain are
the result of biological processes," said NIDA Director, Nora D. Volkow,
M.D. "It is exciting to see the beginnings of a path forward that may
pave the way for treatment interventions that address the motivational
and emotional effects of pain." To investigate what might be underlying
the affective component of pain, researchers at Washington University
in St. Louis built upon prior studies where researchers observed that
rats in pain were more likely to consume higher doses of heroin than
the rats that were not in pain. In addition, their motivation for
natural rewards, such as sugar tablets, was decreased. The new line of investigation sought to uncover the brain circuitry involved in this
pathway, to better understand the relationship between pain and related
changes in one's motivational state.

In this new study, the researchers measured the activity of
dopamine neurons in the ventral tegmental area, part of the brain's
"reward system," which process rewards and orchestrate motivated
behavior. Dopamine neuronal activity was measured in rats while they
pressed a lever with their front paw to receive a sugar tablet (the
reward). To assess the impact of pain on the animals' behavior and
activity of these dopamine neurons, either saline (the control condition)
or a solution that produces a local inflammation (the pain condition)
was injected into the hind paw.

After 48 hours, the researchers found that rats in the pain condition
pressed the lever less to obtain the sugar tablet, demonstrating
a decrease in motivation, and that their dopamine neurons were less
active. They then discovered that the reason the dopamine neurons were
less active was because pain was activating cells from a region of the
brain known as the rostromedial tegmental nucleus (RMTg), which makes
the inhibitory neurochemical GABA, and GABA blocks the activity of the
dopamine neurons.

However, when the researchers artificially restored the activity of
dopamine neurons (through a process called chemogenetics), they were
able to reverse the negative effect of pain on the reward system and
reinstate the motivation to push the lever for the sugar tablet among
the rats in pain, even with the painful stimuli still present.

In additional experiments, the researchers were also able to restore
the activity of the dopamine neurons by reversing the pain-induced hyperactivity of the GABA neurons. Doing so restored the motivation of
rats that were experiencing pain to prefer a sweet solution of sucrose
over water, indicating an improvement in their ability to feel pleasure, despite being in pain.

To the authors' knowledge, this is the first time it has been reported
that pain promotes increased activity of GABA neurons and an "inhibitory pathway" in the reward system of the brain from the RMTg, which causes decreased activity of dopamine cells.

"Pain has primarily been studied at peripheral sites and not in the
brain, with a goal of reducing or eliminating the sensory component
of pain. Meanwhile, the emotional component of pain and associated comorbidities such as depression, anxiety, and lack of ability to feel
pleasure that accompany pain has been largely ignored," said study author
Jose Moro'n-Concepcion, Ph.D., of Washington University in St. Louis.

"It is fulfilling to be able to show pain patients that their mental
health and behavioral changes are as real as the physical sensations,
and we may be able to treat these changes someday," added study author
Meaghan Creed, Ph.D., of Washington University in St. Louis.

========================================================================== Story Source: Materials provided by
NIH/National_Institute_on_Drug_Abuse. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. T Markovic, et al. Pain induces adaptations in ventral tegmental
area
dopamine neurons to drive anhedonia-like behavior. Nature
Neuroscience, 2021 DOI: 10.1038/s41593-021-00924-3 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211018172212.htm

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