IBYME 02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Progesterone reduces the expression of spinal cyclooxygenase-2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain
Autor/es:
CORONEL MF; LABOMBARDA F; DE NICOLA AF; GONZALEZ S
Revista:
European Journal of Pain
Editorial:
Wiley
Referencias:
Año: 2014 vol. 18 p. 348 - 359
ISSN:
1532-2149
Resumen:
Abstract
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-alpha mRNA levels, as an index of NFkB 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-alpha mRNA, suggesting decreased NFkB 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.
