Very few studies examined the outcomes of SCI when 17β-estradiol was administered at 12 h post-injury or later. A low 17β-estradiol dose was ineffective when treatment was initiated at 12 h post-injury, indicating a narrow therapeutic time window. On the other hand, the high 17β-estradiol doses used in some reports raise concerns about the use of such treatments, considering health benefits versus risks in humans. Moreover,most investigations focused on acute or subacute phases and less information is available about the persistence of the effects in chronic phases. Finally, locomotor recovery was the most frequently assessed functional outcome measure after 17β-estradiol treatment, whereas autonomic and sensory functions were infrequently evaluated. This is especially important in view of a report indicating that a GPER agonist induces mechanical hyperalgesia by acting on a subgroup of DRG nociceptive neurons, which project to the dorsal horns (Kuhn et al., 2008). Another investigation showed that intrathecal administration of a GPER agonist promotes painrelated behaviors and elicits spinal nociception (Deliu et al., 2012). Additional studies also support the notion of pronociceptive effects of estrogens in the dorsal spinal cord (Zhang et al., 2012).