Progesterone prevents allodynia after experimental spinal cord injury.
Chronic pain after spinal cord injury represents a therapeutic challenge. Progesterone, a neuroprotective steroid, has been shown to modulate nociceptive thresholds, whereas its effect on neuropathic pain needs to be further explored. In this study, we evaluated whether progesterone could ameliorate pain-associated behaviors in animals subjected to a spinal cord hemisection. The development of mechanical and cold allodynia was assessed in injured male rats treated with daily injections of progesterone or vehicle. The expression of N-methyl-D-aspartate receptor (NMDAR) subunits, protein kinase C gamma (PKCγ), preprodynorphin (ppD), and kappa opioid receptor (KOR), key players in chronic pain mechanisms, was determined in the dorsal spinal cord. Twenty-eight days after injury, all vehicle-treated animals presented allodynic behaviors and a marked increase in NMDAR subunits, PKCγ, and ppD mRNA levels, with no changes in KOR mRNA levels. Progesterone prevented the development of mechanical allodynia and reduced the painful responses to cold stimulation. In correlation with the attenuation of pain behaviors, the steroid prevented NMDAR subunits and PKCγ mRNAs upregulation, did not modify the elevated ppD mRNA levels, but increased KOR expression. In conclusion, progesterone modulates neuropathic pain after spinal cord injury, creating a favorable molecular environment that may decrease spinal nociceptive signaling.


CONCLUSIONS
The present study suggests that progesterone administration could represent an interesting strategy to modulate neuropathic pain circuits after spinal cord injury. Further studies are needed to investigate the potential progesterone receptors involved in these actions.
Coronel
María F
MF
Laboratorio de Bioquímica Neuroendócrina, Instituto de Biología y Medicina Experimental, CONICET, Buenos Aires, Argentina.
Labombarda
Florencia
F
Villar
Marcelo J
MJ
De Nicola
Alejandro F
AF
González
Susana L
SL
D000818:Animals; D004195:Disease Models, Animal; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D009437:Neuralgia / Q000209:etiology / Q000517:prevention & control; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D011374:Progesterone / Q000627:therapeutic use*; D011372:Progestins / Q000627:therapeutic use*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000150:complications*; D014373:Tuberculin / Q000235:genetics / Q000378:metabolism
C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D011372:Progestins; D016194:Receptors, N-Methyl-D-Aspartate; D017473:Receptors, Opioid, kappa; D014373:Tuberculin; D011374:Progesterone; C087857:protein kinase C gamma; D011493:Protein Kinase C