Pain
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P2X7 is a nonselective cation channel activated by extracellular ATP. P2X7 activation contributes to the proinflammatory response to injury or bacterial invasion and mediates apoptosis. Recently, P2X7 function has been linked to chronic inflammatory and neuropathic pain. ⋯ Rs7958311 was associated with experimental pain intensity in the meta-analysis of both cohorts. Significant associations were also found for multisite pain and postoperative pain. Our results strengthen the existing evidence and suggest that P2X7 and genetic variation in the P2RX7-gene may be involved in the modulation of human pain sensitivity.
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Development of chemotherapy-induced neuropathic pain (CINP) compromises the use of chemotherapy and greatly impacts thousands of lives. Unfortunately, there are no Food and Drug Administration-approved drugs to prevent or treat CINP. Neuropathological changes within CNS, including neuroinflammation and increased neuronal excitability, are driven by alterations in neuro-glia communication; but, the molecular signaling pathways remain largely unexplored. ⋯ The effects of MRS5698 were blocked by attenuating IL-10 signaling in rats with intrathecal neutralizing IL-10 antibody and in IL-10 knockout mice. These findings provide new molecular insights implicating astrocyte-based ADK-adenosine axis and nucleotide-binding oligomerization domain-like receptor protein 3 in the development of CINP and IL-10 in the mechanism of action of A3AR agonists. These findings strengthen the pharmacological rationale for clinical evaluation of A3AR agonists already in advanced clinical trials as anticancer agents as an adjunct to chemotherapy.
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Multicenter Study
Racial differences in presentations and predictors of acute pain after motor vehicle collision.
African Americans experience a greater burden of acute pain than non-Hispanic white individuals across of variety of acute medical conditions, but it is unknown whether this is the case after trauma. We evaluated pain, pain-related characteristics (eg, peritraumatic distress), and analgesic treatment in 2 cohorts of individuals (African American [n = 931] and non-Hispanic white [n = 948]) presenting to the emergency department (ED) after a motor vehicle collision. We performed a propensity-matched analysis (n = 796 in each group) to assess racial differences in acute pain in the ED. ⋯ Racial differences in the severity of acute posttraumatic pain after a motor vehicle collision are not explained by factors such as socioeconomic status or crash characteristics. Despite a higher burden of acute pain, African Americans were less likely to receive opioid analgesics and more likely to receive NSAIDs. Further work is needed to understand the relationship between pain severity, disparities in analgesic treatment, and longer term outcomes, such as post-motor vehicle collision chronic pain.