Progesterone reduces the expression of spinal cyclooxygenase-2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain.
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 analyse pain behaviours, the profile of glial cell activation, and IκB-α mRNA levels, as an index of NF-κB transactivation.


METHODS
We used biochemical, immunohistochemical and molecular techniques, as well as behavioural 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 IκB-α mRNA, suggesting decreased NF-κB transactivation. Progesterone administration also attenuated the injury-induced increase in the number of glial fibrillary acidic protein 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 behaviours 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.
Laboratorio de Nocicepción y Dolor Neuropático, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina.
M F
MF
Coronel
F
F
Labombarda
A F
AF
De Nicola
S L
SL
González
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010147:Pain Measurement; D011374:Progesterone / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology; D013119:Spinal Cord Injuries / Q000150:complications / Q000201:enzymology
D011374:Progesterone; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2