• Jennika Veinot, Douglas Cane, and Javeria Ali Hashmi.
• Department of Anesthesia, Pain Management & Perioperative Medicine, Nova Scotia Health Authority, Halifax, Nova Scotia, Canada; Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada.
• J Pain. 2025 Jan 30; 28: 104795104795.

AbstractWorking memory impairments are common in chronic low back pain and are linked to increased pain severity. Reduced working memory may contribute to chronic pain by disrupting the ability to contextualize threat and modulate pain. These processes involve the dorsolateral prefrontal cortex and its interaction with the periaqueductal gray. However, it is unclear how working memory variability impacts activation and connectivity in this pathway and influences chronic pain. Here, we investigated how working memory variability affected activations in the dorsolateral prefrontal cortex - periaqueductal gray pathway during a pain modulation task (schema task) in individuals with chronic low back pain. This task measures how perceived threat of a strong noxious stimulus biases pain perception, referred to as threat bias. Individuals with worse threat bias experienced more widespread pain and less relief. Lower working memory accuracy was associated with abnormally increased activations in the dorsolateral prefrontal cortex and periaqueductal gray during low-threat conditions. In high-threat conditions, low activation in these regions correlated with greater chronic pain and impaired working memory. Baseline functional connectivity between the dorsolateral prefrontal cortex and periaqueductal gray also predicted working memory variability and pain severity. These findings suggest that working memory and pain modulation converge within the dorsolateral prefrontal cortex-periaqueductal gray pathway, where abnormalities contribute to chronic pain. This highlights cognitive-pain interactions and the potential of targeting working memory and this pathway for therapy. Perspective This article presents evidence that low working memory is associated with abnormalities in activations and connectivity in the pain modulation pathways in people with chronic low back pain. These changes predict chronic pain severity indicating a potential association between working memory, pain modulation pathways and chronic pain severity.Copyright © 2025 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.

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