title: Allopregnanolone suppresses diabetes-induced neuropathic pain and motor deficit through inhibition of GABAA receptor down-regulation in the spinal cord of diabetic rats.
abstract: OBJECTIVE
  Painful diabetic neuropathy is associated with hyperexcitability and hyperactivity of spinal cord neurons. However, its underlying pathophysiological mechanisms have not been fully clarified. Induction of excitatory/inhibitory neurotransmission imbalance at the spinal cord seems to account for the abnormal neuronal activity in diabetes. Protective properties of neurosteroids have been demonstrated in numerous cellular and animal models of neurodegeneration.
  
  
  METHODS
  Here, the protective effects of allopregnanolone, a neurosteroid were investigated in an in vivo model of diabetic neuropathy. The tail-flick test was used to assess the nociceptive threshold. Diabetes was induced by injection of 50 mg/kg (IP) streptozotocin. Seven weeks after the induction of diabetes, the dorsal half of the lumbar spinal cord was assayed for the expression of γ2 subunit of GABAA receptor using semiquantitative RT-PCR.
  
  
  RESULTS
  The data shows that allopregnanolone (5 and 20 mg/kg) markedly ameliorated diabetes-induced thermal hyperalgesia and motor deficit. The weights of diabetic rats that received 5 and 20 mg/kg allopregnanolone did not significantly reduce during the time course of study. Furthermore, this neurosteroid could inhibit GABAA receptor down-regulation induced by diabetes in the rat spinal cord.
  
  
  CONCLUSIONS
  The data revealed that allopregnanolone has preventive effects against hyperglycemic-induced neuropathic pain and motor deficit which are related to the inhibition of GABAA receptor down-regulation.
authors: Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center (KNRC), Kerman University of Medical Sciences, Kerman, Iran ; Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
authors: Samira
authors: S
authors: Afrazi
authors: Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
authors: Saeed
authors: S
authors: Esmaeili-Mahani
keywords: Allopregnanolone; Diabetic neuropathy; GABAA receptor; Hyperalgesia; Rats