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-1, TNF-␣, 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-1, 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.
As the geriatric population in the United States continues to age, there will be an increased demand for total hip and total knee arthroplasties (THAs and TKAs). Older patients tend to have more comorbidities and poorer health, and will require post-acute care (PAC) following discharge. The most utilized PAC facilities following THA and TKA are skilled nursing facilities (SNFs), in-patient rehabilitation facilities (IRFs), and home with home health care (HHC). Coordination of care between hospitals and PACs, including the complete transfer of patient information, continues to be a challenge which impacts the quality of care provided by the PACs. The increased demand of hospital resources and PACs by the geriatric population necessitates an improvement in this transition of care process. This review aims to examine the transition of care process currently utilized in the United States for orthopedic surgery patients, and discuss methods for improvement. Employing these approaches will play a key role in improving patient outcomes, decreasing preventable hospital readmissions, and reducing mortality following THA and TKA. The extensive nature of this topic and the ramification of different types of healthcare systems in different countries were the determinant factors limiting our work.
In this study, psychosocial stress was associated with increased pain sensitivity in mice. Development of mechanical allodynia with RSD was blocked by regional analgesia with local anesthetics, Ropivacaine or Liposomal Bupivacaine. Despite blocking mechanical allodynia, these anesthetic interventions did not prevent neuroimmune activation or social avoidance associated with RSD. These data suggest that stress-induced neuroinflammatory changes are not associated with increased sensitivity to pain following RSD. Thus, blocking peripheral nociception was effective in inhibiting enhanced pain signaling without altering stress-induced immune or behavioral responses.
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