Background: Neuropathic 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. Methods: Mice 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. Results: In 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. Conclusion: Betanin treatment appears to ameliorate mechanical hypersensitivity related to CCI-induced NeP in mice by inhibiting microglial activation. Significance: This 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. How to cite this article: Kwankaew N, Okuda H, Aye-Mon A, et al. Antihypersensitivity effect of betanin (red beetroot extract) via modulation of microglial activation in a mouse model of neuropathic pain.
BackgroundDiabetic gastropathy is a complex neuromuscular dysfunction of the stomach that commonly occurs in diabetes mellitus. Diabetic patients often present with upper gastrointestinal symptoms, such as epigastric discomfort or pain. The aim of this study was to assess gastric sensation in streptozocin-induced diabetes mellitus (DM) rats and to determine the contribution of C-C motif chemokine receptor 2 (CCR2) signaling to gastric hyperalgesia.ResultsDM rats showed signs of neuropathy (cutaneous mechanical hyperalgesia) from two weeks after streptozocin administration until the end of the experiment. Accelerated solid gastric emptying was observed at two weeks after streptozocin administration compared to the controls. Intense gastric hyperalgesia also developed in DM rats at two weeks after streptozocin administration, which was significantly reduced after intrathecal administration of the CCR2 antagonist INCB3344. Immunochemical analysis indicated that CCR2 expression was substantially upregulated in small and medium-sized dorsal root ganglia neurons of DM rats, although the protein level of monocyte chemoattractant protein-1, the preferred ligand for CCR2, was not significantly different between the control and DM groups.ConclusionsThese data suggest that CCR2 activation in nociceptive dorsal root ganglia neurons plays a role in the pathogenesis of gastric hyperalgesia associated with diabetic gastropathy and that CCR2 antagonist may be a promising treatment for therapeutic intervention.
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