Progesterone reduces the expression of spinal cycloxygenase-2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain

M.F. CORONEL; F. LABOMBARDA; A. F. DE NICOLA; S.L. GONZALEZ

European Journal of Pain

Wiley

Año: 2014 vol. 18 p. 348 - 359

1532-2149

Background: Spinal cord injury (SCI) results in the development of chronic pain that is refractory to conventional treatment. Progesterone, a neuroprotective steroid, may offer a promising perspective in pain modulation after central injury. Here we explore the impact of progesterone administration on the post-injury inflammatory cascade involving the enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at the spinal cord level. We also analyze pain behaviors, the profile of glial cell activation, and IkB-a  mRNA levels, as an index of NF-kB transactivation. Methods: We used biochemical, immunohistochemical and molecular techniques, as well as behavioral studies, to investigate the effects of progesterone in a well-characterized model of central neuropathic pain. Results: Injured animals receiving progesterone presented reduced mRNA levels of the proinflammatory enzymes, as well as decreased COX-2 activity and nitrite levels, as compared to vehicle-treated injured rats. Further, animals receiving the steroid exhibited lower levels of IkB-a mRNA, suggesting decreased NF-kB transactivation. Progesterone administration also attenuated the injury-induced increase in the number of GFAP and OX-42 positive cells both at early and late time points after injury, and prevented the development of mechanical and thermal allodynia. Further, when injured rats received early progesterone administration for a critical period of time after injury, they did not display allodynic behaviors even after the treatment had stopped. Conclusions: Our results suggest that progesterone, by modulating early neuroinflammatory events triggered after SCI, may represent a useful strategy to prevent the development of central chronic pain.