• Neuroreport · Dec 2011

    The involvement of the neurosteroid allopregnanolone in the antihyperalgesic effect of paroxetine in a rat model of neuropathic pain.

    • Takashi Kawano, Tomohiro Soga, Haidong Chi, Satoru Eguchi, Fumimoto Yamazaki, and Masataka Yokoyama.
    • Department of Anesthesiology and Critical Care Medicine, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783 8505, Japan. takashika@kochi-u.ac.jp
    • Neuroreport. 2011 Dec 21;22(18):984-8.

    AbstractParoxetine increases the levels of neurosteroids, such as allopregnanolone (AP), that influence the excitability of the central nervous system by positive allosteric modulation of γ-aminobutyric acid type A receptors. Here, we investigated the role of AP synthesis on the paroxetine-induced antihyperalgesic effect in a rat model of neuropathic pain induced by lumbar spinal nerve ligation (SNL). Subcutaneous administration of paroxetine in SNL rats, dose-dependently decreased the probability of hyperalgesic response and increased AP levels in the spine but not in either brain or serum. Concomitant treatment with an inhibitor of the AP-synthesizing enzyme, finasteride, attenuated the paroxetine-induced antihyperalgesic effect as well as the paroxetine-induced increase in spinal AP levels. Intrathecal injection of exogenous AP mimicked the analgesic effects of paroxetine in vehicle-treated SNL rats, whereas no additional analgesic effects were observed in paroxetine-treated SNL rats. Our findings suggest that the antihyperalgesic effect of paroxetine in a rat neuropathic pain model is AP-mediated. These results also suggest that pharmacological-based therapies targeting AP synthesis might be a promising treatment for neuropathic pain.

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