Progesterone modulates the expression of spinal ephrin-B2 after peripheral nerve injury: New insights into progesterone mechanisms.

Recent studies have shown that the ephrin/Eph signaling pathway may contribute to the pathology of neuropathic pain. Drugs like progesterone may be used to counteract both thermal hyperalgesia and mechanical allodynia in different models of neuropathic pain. The present study was designed to determine progesterone's modulatory role on neuropathic pain and spinal expression of ephrin-B2 following chronic constriction nerve injury (CCI). Thirty-six adult male Wistar rats were used. The sciatic nerve was chronically constricted. Progesterone (5 mg/kg and 15 mg/kg) was administrated for 10 days (from day 1 up to day10) following sciatic constriction. Behavioral tests were performed before surgery (day 0) and on days 1, 3, 7, and 14 after CCI and before progesterone administration on the same days. Western blotting was performed on days 3, 7, and 14th post-surgery. The findings showed that after CCI, the expression of spinal cord ephrin-B2 increased significantly in parallel with mechanical allodynia and thermal hyperalgesia. Post-injury administration of progesterone (15 mg/kg but not 5) decreased mechanical allodynia, thermal hyperalgesia, and the expression of spinal ephrin-B2. It is concluded that post-injury repeated administration of progesterone could be an effective way of alleviating neuropathic pain by suppressing ephrin-B2 activation and helps to make the better design of steroid-based therapies to inhibit pain after peripheral injury.