GABA disruption in medial prefrontal cortex may be key to emotional impact of chronic pain


By Michael Woodhead

29 Jul 2021

A/Prof Sylvia Gustin

Australian neuroscientists have found evidence to support the hypothesis that chronic pain is associated with emotional problems due pathological changes that cause neurotransmitter dysregulation in the medial prefrontal cortex (mPFC).

Researchers at the Centre for Pain IMPACT,  NeuRA and UNSW Sydney observed significantly decreased levels of glutamate and GABA+ in the mPFC of people with chronic pain, regardless of their type of chronic pain.

The findings support a model of disinhibition where an inability to suppress both pain and emotions are critical in a person’s experience of chronic pain, according to study investigator Associate Professor Sylvia Gustin.

“We have discovered, for the first time, that ongoing pain is associated with a decrease in GABA, an inhibitive neurotransmitter in the medial prefrontal cortex. In other words, there’s an actual pathological change going on,” she said

“A decrease in GABA means that the brain cells can no longer communicate to each other properly. When there’s a decrease in this neurotransmitter, our actions, emotions and thoughts get amplified.”

The research team used neurological imaging with magnetic resonance spectroscopy  to assess GABA content in the medial prefrontal cortex of 24 study participants with chronic pain and an aged matched control group without chronic pain.

A/Prof. Gustin says this relatively small sample size is typical for neurological imaging studies, which are costly to run.

The participants with chronic pain had significantly lower levels of GABA than the control group.  However there was no significant correlation between mPFC GABA+ and glutamate levels and pain intensity, pain variance or pain duration before and during the study.

“In line with our findings, we propose that neurotransmitter dysregulation may lead to chronic reduced inhibition of neuronal activity within the medial prefrontal cortex. This disinhibition may contribute to both emotional dysregulation and the experience of persistent pain,” the study authors said.

They have previously shown that a dysregulation of mPFC glutamate in people with chronic pain can lead to emotional disturbances such as fearfulness, worriedness, pessimism, and sensitivity to criticism and punishment

They postulated a role for glial activation and neuroinflammation in chronic pain that contributed to neurotransmitter dysregulation and, consequent disinhibition.

A/Prof Gustin says she hoped the findings would prove encouraging for people with chronic pain who may be experiencing mental health issues.

“It’s important to remember it’s not you – there’s actually something physically happening to your brain,” she says.

“Everything starts with stress. When someone is in pain, it increases stress hormones like cortisol, which can trigger massive increases in glutamate. This happens during the initial, acute stage of pain.

“Too much glutamate can be toxic to brain cells and brain function. We think this disruption to normal brain function may cause the GABA and glutamate levels to change – and impair a person’s ability to regulate their emotions.”

With no drugs that directly target the GABA and glutamate content in the medial prefrontal cortex, A/Prof. Gustin and her team have recently developed an online emotional recovery program, specifically targeted at people with chronic pain, as a non-pharmaceutical option for treating the neurotransmitter disruption.

“The online therapy program teaches people skills to help self-regulate their negative emotions,” she said.

“The brain can’t dampen down these feelings on its own, but it is plastic – and we can learn to change it.”

The findings are published in the European Journal of Pain.

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