Losartan, an Angiotensin II Type 1 Receptor Antagonist, Alleviates Mechanical Hyperalgesia in a Rat Model of Chemotherapy-Induced Neuropathic Pain by Inhibiting Inflammatory Cytokines in the Dorsal Root Ganglia

In this study, we assessed losartan ’s analgesic effect on paclitaxel-induced neuropathic pain (PINP) in rats and its mechanism of action in dorsal root ganglion (DRG). Rats received intraperitoneal injections of 2 mg/kg paclitaxel on days 0, 2, 4, and 6 and received single or multiple intraperitoneal injections of losartan potassi um dissolved in phosphate-buffered saline at various times. The mechanical thresholds, protein levels of inflammatory cytokines, and cellular location of AT1R and interleukin 1β (IL-1β) in the DRG were assessed with behavioral testing, Western blotting, and immunohistochemistry, respectively. Data were analyzed by two-way repeated-measures analysis of variance for the behavioral test or the Mann-WhitneyU test for the Western blot analysis and immunohistochemistry. Single and multiple injections of losartan ameliorated PINP, and losartan delayed the development of PINP. Paclitaxel significantly increased, and losartan subsequently decreased, the expression levels of inflammatory cytokines, including IL-1 β and tumor necrosis factor α (TNF-α), in the lumbar DRG. AT1R and IL-1β were expressed in both neurons and satellite cells and losartan decreased the intensity of IL-1β in the DRG. Losartan ameliorates PINP by decreasing inflammatory cytokines including IL-1β and TNF-α in the DRG. Our findin gs provide a new or add-on therapy for CIPN patients.
Source: Molecular Neurobiology - Category: Neurology Source Type: research

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