Abstract
More than 450 million people worldwide suffer from diabetes, or 1 in 11 people. Chronic hyperglycemia degrades patients' quality of life and the development of neuropathic pain contributes to the burden of this disease. In this study, we used the mouse model of streptozocin-induced diabetic type 1 neuropathy to assess the analgesic potential of etifoxine. Etifoxine is a prescribed anxiolytic that increases GABAAA receptor function through a direct positive allosteric modulation effect and, indirectly, by stimulating the production of endogenous GABAA receptor positive modulators such as allopregnanolone-type neurosteroids. We show that a post-symptomatic or preventive treatment strongly and durably reduces mechanical hyperalgesia and anxiety in diabetic neuropathic mice. This analgesic and neuroprotective effect on painful symptoms and emotional comorbidities is promising and should now be clinically evaluated.
Highlights
With 463 million affected people worldwide, prevalence of diabetes has drastically increased in the past few decades [1]
We showed that EFX, administered after Painful diabetic neuropathy (PDN) development, or preventively prior to neuropathy induction, successfully and durably limited STZ-induced mechanical allodynia
EFX showed a tendency towards an anxiolytic effect in STZ animals, we were not able to observe strong anxiety-like comorbidities in this model of PDN
Summary
With 463 million affected people worldwide, prevalence of diabetes has drastically increased in the past few decades [1]. Etifoxine analgesia in diabetic neuropathy the University of Strasbourg as recommended by our research organization for open access These data are accessible to the public under the following identifiers: - https://osf.io/9gp68/ Poisbeau, Pierrick (2021): Gazzo et al. Plos_Fig2AC_openfield-light-marble.pzfx. Multifactorial causes conjointly lead to PDN, it is interesting to note here that hyperglycemia-induced mitochondrial dysfunction appears as a key player in PDN development, contributing to the production of free radicals, activation of cell death pathways, and responsible for a depletion in ATP synthesis [7] In this context, we explored the therapeutic potentiel of etifoxine (EFX) in the treatment of PDN pain symptoms and comorbid anxiety. Considering the aforementioned properties of EFX, the aim of this project was to evaluate the properties of post-symptomatic or preventive etifoxine in the relief of PDN pain and anxiety-like symptoms in a rodent model of type 1 diabetes-induced neuropathy
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