How chronic pain leads to maladaptive anxiety?

Neuronal plasticity in chronic pain-induced anxiety revealed.


Pain functions as a biological alarm for impending or actual tissue damage. However, chronic pain is persistent, inescapable stress, which leads to maladaptive emotional states. The comorbidity of chronic pain and mental dysfunctions such as depression and anxiety disorders has long been recognized, but the underlying mechanisms remain poorly understood.

New research from the Hokkaido University uses a mice model to identify how chronic pain leads to maladaptive anxiety. Their study could lead to new treatments for chronic pain and psychiatric disorders such as anxiety disorders and major depressive disorder.

Scientists observed how neuronal circuits were affected by chronic pain in mice. In particular, they used an electrophysiological technique to measure the activities of neurons after four weeks of chronic pain. They discovered that chronic pain generated a neuroplastic alteration in the brain that reduced the neural route connecting the bed nucleus of the stria terminalis (BNST) to the lateral hypothalamus (LH).

They demonstrated that restoring the suppressed activity of this neural circuit decreased chronic pain-induced anxiety using chemogenetics, sophisticated technology for manipulating neuronal activity. These findings suggest that chronic pain-induced functional alterations in the BNST’s neural pathways cause maladaptive anxiety.

Professor Masabumi Minami of the Faculty of Pharmaceutical Sciences at Hokkaido University said“These findings could lead to improved treatment of chronic pain and new therapeutics for anxiety disorder.”

Journal Reference:

  1. Naoki Yamauchi et al. Chronic pain–induced neuronal plasticity in the bed nucleus of the stria terminalis causes maladaptive anxiety. Science Advances, 2022; 8 (17) DOI: 10.1126/sciadv.abj5586
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