Chronic pain and disability after physical trauma, including surgery, is a major public health problem. Surprisingly, recovery from pain after cesarean delivery is more rapid than after similar injuries outside the postpartum period. In animals, recovery from hypersensitivity after surgery is more rapid if surgery occurs in the early postpartum period, and this is blocked by spinal injection of an oxytocin receptor antagonist. This grant was funded to probe in animals and humans the mechanisms and clinical translation of this effect. We are on track to complete the originally proposed studies and have published or submitted 15 manuscripts in the past 3 years. We have also generated novel ideas and methods to increase the impact of this research, including growth curve modeling to more powerfully describe the time course of recovery, novel methods to repeatedly assess motivated, high-intensity movement and pain-related fear of movement in animals, and novel viral vectors to knockdown receptors of interest and to control spinally projecting oxytocinergic neurons and high threshold mechanosensitive nociceptor peripheral neurons. We will apply these novel methods to 2aims in the proposed extension period to determine in animals and in humans: 1. Efficacy and mechanisms of oxytocin against injury-induced pain on movement: We will use novel outcome measures of high-intensity motivated behavior and kinesiophobia in animals to examine the role of oxytocin systems in recovery after surgery, the receptors involved, and methods to augment this recovery-hastening effect. In humans we will test the role of spinal and systemic oxytocin on pain with movement and kinesiophobia with painful physical therapy following surgery. 2. Actions and mechanisms of spinal oxytocin on mechanosensitive input: We will examine the detailed effects of oxytocin on tuning of mechanosensitive inputs, the receptors involved, and the subtype selectivity of these actions in normal animals and those recovering from injury. In healthy humans and those recovering from surgery, we will test the action of spinal and peripheral oxytocin on modality selective input from afferent fiber classes.