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The Unpleasantness of Pain, Brain Circuits, and the Emotional Response

May 15, 2019
Animal study could lead to better understanding of the neurobiology surrounding pain

A PPM Brief

As clinicians and patients alike know, pain is an unpleasant experience, and the unpleasantness of pain is an emotional phenomenon distinct from pain's sensory qualities. Questions remain, however, regarding just how the brain’s affective neural circuits attribute aversion to nociceptive information. In a recent study1 out of Stanford University School of Medicine, researchers explored how the brain processes pain-related emotions.

“Neuroscientists are still unraveling how neural activity across the brain produces the multidimensional experience of pain,” investigator Biafra Ahanonu, PhD, a neuroscientist and researcher at Stanford University, explained to PPM.

(Source: 123RF)

Dr. Ahanou’s team used in vivo neural calcium imaging in mice to identify the brain circuits that respond to pain and test their causal role in motivational behaviors associated with chronic pain. Specifically, by manipulating neural activity in mice encountering noxious stimuli, researchers identified a distinct neural ensemble in the basolateral amygdala that encodes the negative affective valence of pain. Inhibiting this nociceptive ensemble, through an injection of clozapine-N-oxide medication, alleviated pain affective-motivational behaviors without altering the detection of noxious stimuli, withdrawal reflexes, anxiety, or reward. In addition, after inducing sciatic nerve injury in the mice, innocuous stimuli activated the nociceptive ensemble to drive dysfunctional perceptual changes associated with neuropathic pain, including allodynia and hyperalgesia.

“The unpleasantness of pain could be reduced without sacrificing the critical protective reflexive behavior,” Dr. Ahanonu said. “A key next step [will be] to identify whether these cells have unique biological signatures, such as expressing specific receptors, that would allow us to therapeutically target them using small molecules, biologics, or other methods.”

Commenting on the study, David Cosio, PhD, a psychologist in the Pain Clinic at the Jesse Brown VA Medical Center in Chicago, IL, and a member of the PPM Editorial Advisory Board, said that this work, while in animal models, “begins to refine the neurobiology underlying the complexity of the pain experience in the hopes that it may help develop more effective analgesic therapies.”

Last updated on: July 8, 2019
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Chronic Pain and the Psychological Stages of Grief
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