The changing role of descending control of spinal nociception over postnatal development

•Descending projections powerfully control the spinal dorsal horn (DH).•These systems are fundamentally different in early life.•The function of opioidergic and endocannabinoid systems changes in early life.•Pain perturbs the maturation of these systems with life-long consequences on health.•The importance of these systems in human neonatal health has been demonstrated.