Progesterone prevents allodynia after experimental spinal cord injury

CORONEL F; LABOMBARDA F; VILLAR M; DE NICOLA, ALEJANDRO; GONZALEZ S

JOURNAL OF PAIN

CHURCHILL LIVINGSTONE

Año: 2011 vol. 12 p. 71 - 83

1526-5900

Chronic pain after spinal cord injury represents a therapeutic challenge. Progesterone,a neuroprotective steroid, has been shown to modulate nociceptive thresholds, whereas its effecton neuropathic pain needs to be further explored. In this study, we evaluated whether progesteronecould ameliorate pain-associated behaviors in animals subjected to a spinal cord hemisection. The developmentof mechanical and cold allodynia was assessed in injured male rats treated with dailyinjections of progesterone or vehicle. The expression of N-methyl-D-aspartate receptor (NMDAR) subunits,protein kinase C gamma (PKCg), preprodynorphin (ppD), and kappa opioid receptor (KOR), keyplayers in chronic pain mechanisms, was determined in the dorsal spinal cord. Twenty-eight daysafter injury, all vehicle-treated animals presented allodynic behaviors and a marked increase inNMDAR subunits, PKCg, and ppD mRNA levels, with no changes in KOR mRNA levels. Progesteroneprevented the development of mechanical allodynia and reduced the painful responses to coldstimulation. In correlation with the attenuation of pain behaviors, the steroid prevented NMDARsubunits and PKCg mRNAs upregulation, did not modify the elevated ppD mRNA levels, but increasedKOR expression. In conclusion, progesterone modulates neuropathic pain after spinal cord injury,creating a favorable molecular environment that may decrease spinal nociceptive signaling.Perspective: The present study suggests that progesterone administration could represent an interestingstrategy to modulate neuropathic pain circuits after spinal cord injury. Further studies areneeded to investigate the potential progesterone receptors involved in these actions