Zonisamide ameliorates neuropathic pain partly by suppressing microglial activation in the spinal cord in a mouse model.

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.

• Authors: Hiroyuki Koshimizu, Bisei Ohkawara, Hiroaki Nakashima, Kyotaro Ota, Shunsuke Kanbara, Taro Inoue, Hiroyuki Tomita, Akira Sayo, Sumiko Kiryu-Seo, Hiroyuki Konishi, Mikako Ito, Akio Masuda, Naoki Ishiguro, Shiro Imagama, Hiroshi Kiyama, Kinji Ohno
• Journal: Life sciences (Life Sci) Vol. 263 Pg. 118577 (Dec 15 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33058918 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Anticonvulsants
• Cytokines
• Zonisamide

Topics

• Animals
• Anticonvulsants (pharmacology)
• Cytokines (metabolism)
• Disease Models, Animal
• Hyperalgesia (drug therapy, physiopathology)
• Male
• Mice
• Microglia (metabolism)
• Neuralgia (drug therapy, physiopathology)
• Spinal Cord (metabolism)
• Zonisamide (pharmacology)