Betaine Attenuates Chronic Constriction Injury-Induced Neuropathic Pain in Rats by Inhibiting KIF17-Mediated Nociception

Abstract

Kinesin superfamily proteins transport a diverse range of cargo, including excitatory receptors to the dendrite and axon of a neuron via retrograde and anterograde fashions along microtubules, causing central sensitization and neuropathic pain. In this study, we have performed in silico molecular dynamics simulation to delineate the dynamic interaction of betaine with KIF17, a kinesin protein, known to be involved in neuropathic pain. The results from the molecular dynamics study suggest that the betaine−KIF17 complex is stabilized through hydrogen bonding, polar interactions, and water bridges. Findings from in vivo studies suggest a significant increase in pain hypersensitivity, oxido-nitrosative stress, and KIF17 overexpression in the sciatic nerve, dorsal root ganglion (DRG), and spinal cord of nerve-injured rats, which was significantly attenuated on treatment with betaine. Betaine treatment also restored the increased NR2B expressions and levels of proinflammatory cytokines and neuropeptides in the DRG and spinal cord of nerveinjured rats. Findings from the current study suggest that betaine attenuates neuropathic pain in rats by inhibiting KIF17-NR2Bmediated neuroinflammatory signaling.

Neuroprotective Assessment of Betaine against Copper Oxide Nanoparticle-Induced Neurotoxicity in the Brains of Albino Rats: A Histopathological, Neurochemical, and Molecular Investigation

“…These results are in agreement with previous studies of Goma et al and Tohamy et al, , who used different treatment modalities to ameliorate CuO-NP toxicity such as methylene blue and nanocurcumin. However, administration of betaine was able to ameliorate the toxicity in betaine+ CuO-NP-treated rats by increasing the locomotor activity due to its antioxidant activity as reported in many studies. , In the rearing activity, there was no statistical significance between those exposed to CuO-NPs and those cotreated with betaine.…”

“…However, administration of betaine was able to ameliorate the toxicity in betaine+ CuO-NP-treated rats by increasing the locomotor activity due to its antioxidant activity as reported in many studies. 37,38 In the rearing activity, there was no statistical significance between those exposed to CuO-NPs and those cotreated with betaine. Moreover, in the Y-maze test as portrayed in Table 1, CuO-NPs intoxicated rats showed a significant reduction in the locomotor activity as evidenced by the significant reduction in the numbers of arm entries compared to the control.…”

Making the case for prophylactic use of betaine to promote brain health in young (15–24 year old) athletes at risk for concussion

“…Betaine’s anti-inflammatory properties may also be related to preventing endoplasmic reticulum stress resulting from mis-/un-folded proteins, through inhibition of caspase aggregation mediating apoptosis ( Xie et al, 2020 ) and preventing inflammasome assembly ( Zhao et al, 2018 ; Zhang et al, 2022 ). Indeed, recent data on the anti-inflammatory role of betaine has been linked with attenuation of pain ( Hassanpour et al, 2020 ; Nobari et al, 2021a ; Tiwari and Hemalatha, 2022 ) and with treatment of affective disorders like depression ( Chen et al, 2021 ; Zhang et al, 2022 ). Therefore–in addition to regulating cell volume, fluid dynamics, etc.–betaine, as an osmolyte, plays an essential role in protein folding and aggregation that benefit CNS physiology and affect pathogenesis.…”

“…Finally, betaine has already been used clinically to improve cognitive function in neurodegenerative disorders, including dementia, Alzheimer’s, and Parkinson’s ( Eussen et al, 2007 ; Ilyas et al, 2022 ). In animal models, betaine has recently been associated with various other neuroprotective roles such as in post-traumatic syringomyelia ( Pukale et al, 2021 ), in neuropathic pain management ( Hassanpour et al, 2020 ; Tiwari and Hemalatha, 2022 ), and in affective disorders ( Qu et al, 2020 ; Chen et al, 2021 ; Haramipour et al, 2021 ; Jeyhoonabadi et al, 2022 ; Zhang et al, 2022 ).…”