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  • Title: Zonisamide ameliorates neuropathic pain partly by suppressing microglial activation in the spinal cord in a mouse model.
    Author: Koshimizu H, Ohkawara B, Nakashima H, Ota K, Kanbara S, Inoue T, Tomita H, Sayo A, Kiryu-Seo S, Konishi H, Ito M, Masuda A, Ishiguro N, Imagama S, Kiyama H, Ohno K.
    Journal: Life Sci; 2020 Dec 15; 263():118577. PubMed ID: 33058918.
    Abstract:
    Neuropathic pain is caused by a lesion or a functional impairment of the sensory nervous system and allodynia is one of the frequently observed symptoms in neuropathic pain. Allodynia represents abnormal pain due to a non-noxious stimulus that does not normally provoke pain. Cellular mechanisms underlying neuropathic pain remain mostly elusive, and partial pain relief can be achieved in a limited number of patients by antidepressants, anticonvulsants topical anesthetics, and others. Zonisamide (ZNS) is widely used as an anti-epileptic and anti-Parkinson's disease drug. A recent report shows that ZNS suppresses neuropathic pain associated with diabetes mellitus in a mouse model. We made a mouse model of neuropathic pain in the hindlimb by cutting the nerve at the intervertebral canal at lumbar level 4 (L4). At 28 days after nerve injury, ZNS ameliorated allodynic pain, and reduced the expression of inflammatory cytokines and the nerve injury-induced increase of Iba1-positive microglia in the spinal dorsal horn at L4. In BV2 microglial cells, ZNS reduced the number of lipopolysaccharide-induced amoeboid-shaped cells, representing activated microglia. These results suggest that ZNS is a potential therapeutic agent for neuropathic pain partly by suppressing microglia-mediated neuroinflammation.
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