Browsing by Author "Pilapil, Alexandra"

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    The Role of Microglial P2X7 Receptor Phosphorylation in Neuropathic Pain
    (2016) Pilapil, Alexandra; Trang, Tuan; Zamponi, Gerald; Pang, Daniel; Gilch, Sabine
    Neuropathic pain is a debilitating chronic pain condition that can arise because of injury to a peripheral nerve. The lack of effective therapies for neuropathic pain demands a better understanding of the underlying mechanisms. Converging evidence suggests that neuropathic pain is caused by aberrant cellular and molecular changes within the central nervous system. Microglia and P2X7 receptors (P2X7Rs) are spinal targets implicated in neuropathic pain, but the core mechanisms that modulate microglial P2X7R activity remain obscure. We identified Y382-384 within the P2X7R C-terminal domain as a putative phosphorylation site that underlies nerve injury-induced mechanical allodynia in a sex-dependent mechanism. Thus, site-specific tyrosine phosphorylation of P2X7R in microglia is a novel spinal determinant involved in neuropathic pain for male animals. The findings of this study provide evidence for microglial-mediated sex differences in neuropathic pain, which further reinforces the importance of including male and female subjects in preclinical pain research.