Exploiting endogenous opioids: lessons learned from endomorphin 2 in the female rat.

•Activating endogenous opioid systems can produce analgesia while avoiding opioid abuse.•Opioid drugs and native opioid peptides have different profiles of action.•Mechanisms mediating antinociception can differ over the reproductive cycle.•Targeting spinal estrogenic and glutamatergic signaling in a physiological state-dependent manner can harness endogenous opioid analgesia.