It has recently been demonstrated that the spinal cord (SC) is an active production center of neuroactive steroids including pregnenolone, dehydroepiandrosterone, progesterone and allopregnanolone. Indeed, anatomical, cellular and biochemical investigations have shown that the SC dorsal horn (DH), a pivotal structure in nociception, contains various active steroidogenic enzymes such as cytochrome P450side-chain-cleavage, cytochrome P450c17, 3beta-hydroxysteroid dehydrogenase, 5alpha-reductase and 3alpha-hydroxysteroid oxido-reductase. Reviewed here are several data obtained with in vitro and vivo experiments showing that endogenous steroids synthesized in the SC are involved in the modulation of nociceptive mechanisms. Various approaches were used as the real-time polymerase chain reaction after reverse transcription to determine the effects of neuropathic pain on the expression of genes encoding steroidogenic enzymes in the DH. Combination of the pulse-chase technique with high performance liquid chromatography and continuous flow scintillation detection allowed investigations of the impact of noxious signals on the activity of steroid-producing enzymes in the SC in vitro. Radioimmunological analyses of spinal tissue extracts contributed to determine the link between the painful state and endogenous steroid secretion in the SC in vivo. Finally, the physiological relevance of the modification of endogenous steroid formation in the SC during painful situation was discussed.