Progesterone prevents chronic pain after spinal cord injury

M.F. CORONEL

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Sociedad Argentina de Investigación en Neurociencias

Neuropathic pain develops in nearly 70% of patients with spinal cord injury (SCI). Currently available pharmacotherapy has limited efficacy and adverse side effects. We have recently shown that progesterone (PG), a neuroprotective steroid, may offer a promising perspective in neuropathic pain modulation. After SCI a state of central sensitization is established at the dorsal horn, involving both the hyperexcitability of neurons in the pain pathway, mainly mediated by glutamate NMDA receptor, and the activation of glia cells, with the subsequent release of pro-nociceptive mediators. By using biochemical, immunohistochemical and molecular techniques, we investigated the impact of SCI and PG administration on several markers of neuronal and glial cell activation at the dorsal horn level. We also evaluated the development of allodynia (pain elicited by innocuous stimuli). SCI-animals developed mechanical and thermal allodynia in their hindpaws. Interestingly, rats receiving PG did not display allodynic behaviors. After SCI, a significant increase in the mRNA levels of NMDA receptor subunits (NR1, NR2A, NR2B) and PKCγ, enzyme involved in the activation of NR1, was observed in the dorsal spinal cord. In addition, a marked increase in the number of NR1, pNR1 and PKCγ immunoreactive neurons was detected. In correlation with the observed attenuation of pain, injured animals treated with PG showed reduced expression of all these markers. PG administration also attenuated the injury-induced increase in the number of GFAP-positive astrocytes and OX42-positive microglial cells. Furthermore, PG-treated animals presented significantly lower mRNA levels of the proinflammatory cytokines IL-1b, IL-6 and TNF-a, their receptors, and the proinflammatory enzymes COX-2 and iNOS, as compared to vehicle-treated injured rats. Our results suggest that PG, by modulating neuronal excitability and glial activation triggered after SCI, may represent a useful strategy to prevent neuropathic pain.