Open AccessThe non-benzodiazepine anxiolytic etifoxine limits mechanical allodynia and anxiety-like symptoms in a mouse model of streptozotocin-induced diabetic neuropathy
Author(s) -
Géraldine Gazzo,
Marlene Salgado Ferrer,
Pierrick Poisbeau
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0248092
Subject(s) - neuroactive steroid , anxiolytic , neuropathic pain , medicine , gabaa receptor , pharmacology , diabetic neuropathy , analgesic , allodynia , hyperalgesia , allopregnanolone , benzodiazepine , diabetes mellitus , endocrinology , receptor , nociception
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.