Neurosteroids and neuropathic pain management: Basic evidence and therapeutic perspectives.

ABSTRACT

Complex mechanisms involved in neuropathic pain that represents a major health concern make its management complicated. Because neurosteroids are bioactive steroids endogenously synthesized in the nervous system, including in pain pathways, they appear relevant to develop effective treatments against neuropathic pain. Neurosteroids act in paracrine or autocrine manner through genomic mechanisms and/or via membrane receptors of neurotransmitters that pivotally modulate pain sensation. Basic studies which uncovered a direct link between neuropathic pain symptoms and endogenous neurosteroid production/regulation, paved the way for the investigations of neurosteroid therapeutic potential against pathological pain. Concordantly, antinociceptive properties of synthetic neurosteroids were evidenced in humans and animals. Neurosteroids promote peripheral analgesia mediated by T-type calcium and gamma-aminobutyric acid type A channels, counteract chemotherapy-induced neuropathic pain and ameliorate neuropathic symptoms of injured spinal cord animals by stimulating anti-inflammatory, remyelinating and neuroprotective processes. Together, these data open interesting perspectives for neurosteroid-based strategies to manage/alleviate efficiently neuropathic pain.