CONICET | Buscador de Institutos y Recursos Humanos

Neuropathic pain develops in nearly 70% of patients with spinal cord injury (SCI). These patients, already burdened with the disability of paralysis, emotional trauma and spasticity, must contend with severe unrelenting pain that is refractory to conventional treatment. The precise mechanisms underlying neuropathic pain after SCI remain elusive. However, central sensitization involving the hyperexcitability of dorsal horn neurons in the pain pathway is known to be mediated by N-Methyl-D-Aspartate receptor (NMDAR), and the activation of glial cells, with the subsequent release of pro-nociceptive mediators, also play a crucial role. Previous work from our laboratory and others has shown that progesterone (PG), a neuroactive steroid, exerts neuroprotective and promyelinating actions in the injured spinal cord. Further, we have recently reported that this steroid may offer a promising perspective in pain modulation. In this work, we used a recognized model of central neuropathic pain to study the effects of PG on the expression of NMDAR subunits and protein kinase C (PKC), both key players in the process of central sensitization at the spinal level. Injured animals receiving vehicle showed well-established mechanical and thermal allodynia (pain elicited by innocuous stimuli), and a significant increase in the spinal expression of all the NMDAR subunits and PKC. Interestingly, animals receiving PG did not develop mechanical allodynia and showed reduced sensitivity to cold stimulation. In these animals, the expression of NMDAR subunits and PKC remained similar to control levels. In addition, PG was also able to reduce glial cell activation and the production of proinflammatory cytokines which strongly contribute to the pathology of central neuropathic syndromes. Our current investigations add new data to further stimulate the study of neuroactive steroids-based therapies and may open new avenues to prevent chronic pain after SCI.