• Nichakarn Kwankaew, Hiroaki Okuda, Aye Aye-Mon, Tatsuya Ishikawa, Kiyomi Hori, Phattarapon Sonthi, Yu Kozakai, and Noriyuki Ozaki.
• Department of Functional Anatomy, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
• Eur J Pain. 2021 Sep 1; 25 (8): 1788-1803.

BackgroundNeuropathic pain (NeP) medications have several side effects that affect NeP patients' quality of life. Betanin, the most common betacyanin pigment, has been shown to have potent antioxidant and anti-inflammatory properties in vivo; thus, it has potential as a healthcare treatment. In this study, we focused on betanin (red beetroot extract) as a potential therapy for NeP.MethodsMice model of NeP were made by chronic constriction injury (CCI), and the development of mechanical hypersensitivity was confirmed using the von Frey test. Motor coordination and locomotor activity were assessed using open field tests and rotarod tests, respectively. The expression level of glial markers in the spinal cords was analyzed by immunostaining. The direct effects of betanin on microglial cells were investigated using primary cultured microglial cells.ResultsIn CCI model mice, repeated betanin treatment, both intraperitoneally and orally, attenuated developing mechanical hypersensitivity in a dose-dependent manner without impairing motor coordination. Betanin treatment also attenuated mechanical hypersensitivity that had developed and prevented the onset of mechanical hypersensitivity in CCI mice. Microglial activation in the spinal cord is known to play a key role in the development of NeP; betanin treatment reduced CCI-induced microglial activation in the spinal cord of model mice. Moreover, in primary microglia cultured cells, the activation of microglia by lipopolysaccharide application was suppressed by betanin treatment.ConclusionBetanin treatment appears to ameliorate mechanical hypersensitivity related to CCI-induced NeP in mice by inhibiting microglial activation.SignificanceThis article supports findings of the effect of betanin on NeP and provides a potential therapeutic candidate for NeP. Furthermore, elucidating the underlying mechanism of the effect of betanin on microglial activation could assist the development of new treatments for chronic pain.© 2021 European Pain Federation - EFIC®.

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