Early repeated administration of progesterone improves the recovery of neuropathic pain and modulates spinal 18 kDa-translocator protein (TSPO) expression

Although progesterone was reported to be a neuroprotective agent against injuries to the nervous system, including the peripheral neuropathy, the mechanisms of its dose or timing-related effects remain unclear. Translocator protein (TSPO) is predominantly located in the mitochondrial outer membrane and has been recently implicated in modulation of several brain injuries and nociception. This experiment was conducted using a rat model of L5 spinal nerve ligation (SNL) to observe the effects of progesterone against allodynia development in an 84-day period and to explore the spinal TSPO expression after treatment. Our results demonstrated that a 10-day progesterone treatment started right after injury at a dose of 15 mg/kg/d or more could significantly increase the mechanical thresholds within the 84-day observation period. Moreover, increased TSPO expression was observed in the ipsilateral spinal dorsal horn after SNL surgery and reached its peak on Day 14. A treatment regimen of pharmacological progesterone augmented this spinal TSPO activation and expression before Day 28 and after Day 56. Both the anti-nociception and TSPO activation augment effect of progesterone were completely abolished by 5 alpha-reductase inhibitor finasteride but not progesterone receptor antagonist mifepristone. These results indicate that early repeated administration of progesterone could improve the recovery of neuropathic pain and modulate spinal TSPO activation which were dependent on its 5 alpha-reductase metabolites. (C) 2014 Elsevier Ltd. All rights reserved.