The Impact of Stored Painful Memories in Prefrontal Cortex on Future Pain Experience

May 12, 2023 feature

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by Ingrid Fadelli , Medical Xpress

While pain and fear are distinct experiences, previous studies have shown that they can sometimes be closely related. For example, in dangerous or life-threatening situations, acute fear can suppress the perception of pain in many animals and humans, allowing them to concentrate fully on what is happening to them.

Conversely, research indicates that high levels of pain in humans can create associative fear memories that cause them to be fearful of situations linked to the pain they experienced. These memories may increase sensitivity to pain or lead to the development of unhelpful behavioral patterns aimed at avoiding pain.

The increase in the intensity of pain perception after painful past experiences could be connected to anticipatory fear of pain. However, the exact neural mechanisms underlying this process are still not well understood.

Recently, researchers at Heidelberg University conducted a study to understand which regions of the mouse brain store painful experiences and how these memories affect future pain experiences. Their findings, published in Nature Neuroscience, suggest that these memories are stored in the prefrontal cortex, the area covering the front part of the mammalian brain.

The researchers conducted experiments on adult mice using a neural tagging method and optogenetic techniques. The mice received small electric shocks on their feet and were conditioned to become fearful of receiving these shocks again. The team used optogenetic techniques to activate or suppress different neural circuits, determining how this would affect the mice's sensitivity to pain.

'We show in mice that long-term associative fear memory stored in neuronal engrams in the prefrontal cortex determines whether a painful episode shapes pain experience later in life,' the researchers wrote in their paper.

'Furthermore, under conditions of inflammatory and neuropathic pain, prefrontal fear engrams expand to encompass neurons representing nociception and tactile sensation, leading to pronounced changes in prefrontal connectivity to fear-relevant brain areas. Conversely, silencing prefrontal fear engrams reverses chronically established hyperalgesia and allodynia.'

The study outlines some of the neural mechanisms that may be responsible for perpetuating chronic pain resulting from fearful associative memories of past pain. These findings have the potential to inspire the development of new therapeutic interventions for chronic pain manifestations that may be linked to previous painful experiences. These interventions could combine cognitive behavioral therapy with drugs targeting neural circuits in the prefrontal cortex.

'These results reveal that a discrete subset of prefrontal cortex neurons can account for the debilitating comorbidity of fear and chronic pain and show that attenuating the fear memory of pain can alleviate chronic pain itself,' the researchers wrote in their paper. 'Our study provides causal evidence for diminishing pathological pain by overpowering anticipatory fear and gives an impetus for developing interventions targeting prefrontal circuitry in individuals with chronic pain and comorbid fear.'

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