• Zoë Dworsky-Fried, Christian A Faig, Holly A Vogel, Bradley J Kerr, and TaylorAnna M WAMWDepartment of Pharmacology, University of Alberta, Edmonton, AB, Canada.Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton,.
• Department of Pharmacology, University of Alberta, Edmonton, AB, Canada.
• Pain. 2022 Jan 1; 163 (1): e49e61e49-e61.

AbstractChronic pain is a highly prevalent symptom associated with the autoimmune disorder multiple sclerosis (MS). The central nucleus of the amygdala plays a critical role in pain processing and modulation. Neuropathic pain alters nociceptive signaling in the central amygdala, contributing to pain chronicity and opioid tolerance. Here, we demonstrate that activated microglia within the central amygdala disrupt nociceptive sensory processing and contribute to pain hypersensitivity in experimental autoimmune encephalomyelitis (EAE), the most frequently used animal model of MS. Male and female mice with EAE exhibited differences in microglial morphology in the central amygdala, which was associated with heat hyperalgesia, impaired morphine reward, and reduced morphine antinociception in females. Animals with EAE displayed a lack of morphine-evoked activity in cells expressing somatostatin within the central amygdala, which drive antinociception. Induction of focal microglial activation in naïve mice via injection of lipopolysaccharide into the central amygdala produced a loss of morphine analgesia in females, similar to as observed in EAE animals. Our data indicate that activated microglia within the central amygdala may contribute to the sexually dimorphic effects of morphine and may drive neuronal adaptations that lead to pain hypersensitivity in EAE. Our results provide a possible mechanism underlying the decreased efficacy of opioid analgesics in the management of MS-related pain, identifying microglial activation as a potential therapeutic target for pain symptoms in this patient population.Copyright © 2021 International Association for the Study of Pain.

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