Intrathecal Lamotrigine Attenuates Mechanical Allodynia and Suppresses Microglial and Astrocytic Activation in a Rat Model of Spinal Nerve Ligation

다국어 초록 (Multilingual Abstract)

Purpose: Lamotrigine, a novel anticonvulsant, is a sodium channel blocker that is efficacious in certain forms of neuropathic pain. Recently, microglial and astrocytic activation has been implicated in the development of nerve injury-induced neuropathic pain. We have assessed the effects of continuous intrathecal administration of lamotrigine on the development of neuropathic pain and glial activation induced by L5/6 spinal-nerve ligation in rats. Materials and Methods: Following left L5/6 spinal nerve ligation (SNL), Sprague-Dawley male rats were intrathecally administered lamotrigine (24, 72, or 240 μg/day) or saline continuously for 7 days. Mechanical allodynia of the left hind paw to von Frey filament stimuli was determined before surgery (baseline) and once daily for 7 days postoperatively. On day 7, spinal activation of microglia and astrocytes was evaluated immunohistochemically,using antibodies to the microglial marker OX-42 and the astrocyte marker glial fibrillary acidic protein (GFAP). Results: Spinal-nerve ligation induced mechanical allodynia in saline-treated rats, with OX-42 and GFAP immunoreactivity being significantly increased on the ipsilateral side of the spinal cord. Continuously administered intrathecal lamotrigine (240 μg/day) prevented the development of mechanical allodynia, and lower dose of lamotrigine (72 μg/day) ameliorated allodynia. Intrathecal lamotrigine (72 and 240 μg/day) inhibited nerve ligation-induced microglial and astrocytic activation, as evidenced by reduced numbers of cells positive for OX-42 and GFAP. Conclusion: Continuously administered intrathecal lamotrigine blocked the development of mechanical allodynia induced by SNL with suppression of microglial and astrocytic activation. Continuous intrathecal administration of lamotrigine may be a promising therapeutic intervention to prevent neuropathy.

참고문헌 (Reference)

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