Microglia Promote Increased Pain Behavior through Enhanced Inflammation in the Spinal Cord during Repeated Social Defeat Stress
| Autor: | Daniel B. McKim, John F. Sheridan, Timothy D. Faw, Michelle L. Humeidan, Jessica K. Lerch, Jonathan P. Godbout, Caroline M. Sawicki, D. Michele Basso, January K. Kim, Kathryn M. Madalena, Michael D. Weber |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Anxiety Social Environment Spinal Cord Diseases Social defeat Mice 03 medical and health sciences 0302 clinical medicine Lumbar Internal medicine medicine Animals Organic Chemicals Spinal Cord Injuries Research Articles Inflammation CD11b Antigen Behavior Animal Microglia business.industry General Neuroscience Chronic pain medicine.disease Spinal cord Mice Inbred C57BL Lumbar Spinal Cord 030104 developmental biology medicine.anatomical_structure Nociception Allodynia Endocrinology Gene Expression Regulation Spinal Cord Hyperalgesia Receptors Granulocyte-Macrophage Colony-Stimulating Factor Chronic Pain medicine.symptom business Stress Psychological 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Neuroscience. 39:1139-1149 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2785-18.2018 |
| Popis: | Clinical studies indicate that psychosocial stress contributes to adverse chronic pain outcomes in patients, but it is unclear how this is initiated or amplified by stress. Repeated social defeat (RSD) is a mouse model of psychosocial stress that activates microglia, increases neuroinflammatory signaling, and augments pain and anxiety-like behaviors. We hypothesized that activated microglia within the spinal cord facilitate increased pain sensitivity following RSD. Here we show that mechanical allodynia in male mice was increased with exposure to RSD. This stress-induced behavior corresponded with increased mRNA expression of several inflammatory genes, including IL-1β, TNF-α, CCL2, and TLR4 in the lumbar spinal cord. While there were several adhesion and chemokine-related genes increased in the lumbar spinal cord after RSD, there was no accumulation of monocytes or neutrophils. Notably, there was evidence of microglial activation selectively within the nociceptive neurocircuitry of the dorsal horn of the lumbar cord. Elimination of microglia using the colony stimulating factor 1 receptor antagonist PLX5622 from the brain and spinal cord prevented the development of mechanical allodynia in RSD-exposed mice. Microglial elimination also attenuated RSD-induced IL-1β, CCR2, and TLR4 mRNA expression in the lumbar spinal cord. Together, RSD-induced allodynia was associated with microglia-mediated inflammation within the dorsal horn of the lumbar spinal cord.SIGNIFICANCE STATEMENTMounting evidence indicates that psychological stress contributes to the onset and progression of adverse nociceptive conditions. We show here that repeated social defeat stress causes increased pain sensitivity due to inflammatory signaling within the nociceptive circuits of the spinal cord. Studies here mechanistically tested the role of microglia in the development of pain by stress. Pharmacological ablation of microglia prevented stress-induced pain sensitivity. These findings demonstrate that microglia are critical mediators in the induction of pain conditions by stress. Moreover, these studies provide a proof of principle that microglia can be targeted as a therapeutic strategy to mitigate adverse pain conditions. |
| Databáze: | OpenAIRE |
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