Phase-Specific Differential Regulation of Mechanical Allodynia in a Murine Model of Neuropathic Pain by Progesterone

Progesterone's effects on neuropathic pain in mice following sciatic nerve injury were found to be phase-specific. During the early phase of pain development, progesterone worsened mechanical allodynia and increased spinal glial fibrillary acidic protein (GFAP) expression, an effect that was blocked by a P450c17 inhibitor but not by a 5α-reductase inhibitor. Conversely, during the chronic pain maintenance phase, progesterone reduced pain and GFAP expression, an effect reversed by a 5α-reductase inhibitor but not by a P450c17 inhibitor. These effects were not influenced by a progesterone receptor antagonist. The study suggests that progesterone may exacerbate pain shortly after nerve injury by activating P450c17, but it can alleviate chronic neuropathic pain through 5α-reductase activity, independent of progesterone receptors.