Progesterone reduces allodynia in animals with sciatic nerve injury: possible involvement of protein kinase C and N-methyl-D-aspartate subunit 1

M.F. CORONEL; F. LABOMBARDA; P. ROIG; M.J. VILLAR; A.F. DE NICOLA; S.L. GONZALEZ

Atenas

Congreso; Third International Congress on Neuropathic Pain; 2010

International Association for the Study of Pain

Neuropathic pain still remains a therapeutic challenge. Progesterone, a neuroactive steroid with neuroprotective functions, may offer a promising perspective in pain modulation. In the present work, we evaluated the effect of progesterone administration on the development of neuropathic pain-associated behaviors in animals subjected to a sciatic nerve injury. The spinal expression of NMDA receptor subunit 1 (NR1), its phosphorylated form (pNR1) and the gamma isoform of protein kinase C (PKCg), all key players in chronic pain mechanisms, was also investigated. Male Sprague-Dawley rats were subjected to a sciatic nerve chronic constriction injury or sham-operated and treated with daily subcutaneous injections of progesterone or vehicle. The development of hindpaw mechanical and thermal allodynia was assessed using the von Frey and Choi tests. Eighteen days after injury, the number of neurons exhibiting PKCã, NR1 or pNR1 immunoreactivity was determined in lumbar sections of the spinal cord. As expected, injured animals developed ipsilateral mechanical and thermal allodynia. Interestingly, injured rats treated with progesterone did not develop mechanical allodynia and showed a significantly lower number of painful responses to cold stimulation. A marked increase in the number of NR1, pNR1 and PKCã immunoreactive neurons was observed in the ipsilateral dorsal horn of injured animals. In correlation with the observed attenuation of pain behaviors, progesterone administration significantly reduced the number of neurons expressing each of the molecules evaluated. Our results show that progesterone, by targeting spinal mechanisms, reduces allodynia and thus may be useful in the treatment of chronic pain states (M808 and M016 UBACYT, PIP 112-200801-00542).