Central amygdala inflammation drives pain hypersensitivity and attenuates morphine analgesia in experimental autoimmune encephalomyelitis
| Autor: | Bradley J. Kerr, Christian A Faig, Anna M.W. Taylor, Zoë Dworsky-Fried, Holly A Vogel |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Encephalomyelitis Autoimmune Experimental Amygdala Mice medicine Animals Humans Inflammation Morphine business.industry Central nucleus of the amygdala Multiple sclerosis Central Amygdaloid Nucleus Experimental autoimmune encephalomyelitis Chronic pain Drug Tolerance medicine.disease Analgesics Opioid Anesthesiology and Pain Medicine medicine.anatomical_structure Nociception Neurology Hyperalgesia Immunology Neuropathic pain Neuralgia Female Neurology (clinical) Analgesia business medicine.drug |
| Zdroj: | Pain. 163:e49-e61 |
| ISSN: | 1872-6623 0304-3959 |
| DOI: | 10.1097/j.pain.0000000000002307 |
| Popis: | Chronic 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 naive 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. |
| Databáze: | OpenAIRE |
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