Articles: chronic.
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The anterior cingulate cortex (ACC) plays a crucial role in the perception of pain. It is consistently activated by noxious stimuli and its hyperactivity in chronic pain indicates plasticity in the local neuronal network. However, the way persistent pain effects and modifies different neuronal cell types in the ACC and how this contributes to sensory sensitization is not completely understood. ⋯ Accordingly, it was sufficient to enhance the excitability of these neurons chemogenetically in the inflammatory pain condition to induce hypoalgesia. These findings suggest a cell type-specific effect on the descending control of nociception and a cellular mechanism for pain-induced analgesia. Furthermore, increased excitability in this neuronal population is hypoalgesic rather than hyperalgesic.
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Anesthesia and analgesia · Oct 2024
The Effect of Pexidartinib on Neuropathic Pain via Influences on Microglia and Neuroinflammation in Mice.
Chronic pain is a debilitating medical condition that lacks effective treatments. Increasing evidence suggests that microglia and neuroinflammation underlie pain pathophysiology, which therefore supports a potential strategy for developing pain therapeutics. Here, our study is testing the hypothesis that the promise of pain amelioration can be achieved using the small-molecule pexidartinib (PLX-3397), a previously food and drug administration (FDA)-approved cancer medicine and a colony-stimulating factor-1 receptor (CSF-1R) inhibitor that display microglia-depleting properties. ⋯ Collectively, our study showed PLX-3397-related efficacy in ameliorating pain linked to the reduction of microglia and neuroinflammation in mice. Furthermore, our research provided new proof-of-concept data supporting the promise of testing PLX-3397 as an analgesic.