Progesterone prevents nerve injury-induced allodynia and spinal NMDA receptor upregulation in rats

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

PAIN MEDICINE

WILEY-BLACKWELL PUBLISHING, INC

Año: 2011 vol. 12 p. 1249 - 1261

1526-2375

Background: Peripheral nerve injury-evoked neuropathic pain still remains a therapeutic challenge. Recent studies support the notion that progesterone, a neuroactive steroid, may offer a promising perspective in pain modulation. Objectives: Evaluate the effect of progesterone administration on the development of neuropathic pain-associated allodynia and on the spinal expression of N-Methyl-D-Aspartate Receptor subunit 1 (NR1), its phosphorylated form (pNR1) and the gamma isoform of protein kinase C (PKCã), all key players in the process of central sensitization, in animals subjected to a sciatic nerve constriction. Methods: Male Sprague-Dawley rats were subjected to a sciatic nerve single ligature constriction and treated with daily subcutaneous injections of progesterone (16 mg/kg) or vehicle. The development of hindpaw mechanical and thermal allodynia was assessed using the von Frey and Choi tests respectively. Twenty two days after injury, the number of neuronal profiles exhibiting NR1, pNR1 or PKCã immunoreactivity was determined in the dorsal horn of the lumbar spinal cord. Results: Injured animals receiving progesterone did not develop mechanical allodynia and showed a significantly lower number of painful responses to cold stimulation. In correlation with the observed attenuation of pain behaviors, progesterone administration significantly reduced the number of NR1, pNR1 and PKCg immunoreactive neuronal profiles. Conclusions: Our results show that progesterone prevents allodynia in a rat model of sciatic nerve constriction, and reinforce its role as a potential treatment for neuropathic pain.