The postnatal period is a critical time for developing pain pathways. Over the first weeks of life nociceptive circuits are shaped, endogenous pain control systems are activated and pain behaviour is organised (Fitzgerald, 2005). As in other sensory systems, these processes are strongly influenced by sensory experience and as such could be viewed as a form of learning. For the pain system, this creates a special vulnerability. Repeated peripheral tissue damage, such as arises in neonatal intensive care or surgery, alters the physiological balance of sensory input and changes the course of somatosensory development, pain perception and behaviour. We propose that the key to the plasticity of immature nociceptive circuits lies in the late postnatal maturation of endogeous pain control systems within the CNS. This presentation therefore focuses upon our recent data on the maturation of inhibitory controls over the postnatal period. In adults, pain perception and behaviour is powerfully controlled at the level of the spinal cord by local inhibitory circuits and by descending activity from brainstem nuclei. An important source of spinal pain modulation comes from dorsal horn glycinergic inhibitory interneurons which can powerfully control evoked spike activity and regulate dorsal horn cell receptive field size. This local inhibition is recruited by the afferent input itself and in adults, its failure can lead to acute and chronic pain (Zeilhofer and Zeilhofer, 2008). We have previously shown that dorsal horn inhibitory processing undergoes considerable postnatal maturation at the synaptic (Ingram et al. 2008) and circuit (Bremner and Fitzgerald, 2008) level. In addition there are little or no glycinergic PSCs in neonatal lamina II cells and inhibitory neurotransmission in lamina II of the dorsal horn is dominated by GABAergic transmission in the early stages of development (Baccei et al. 2005). Here we will present new data on the role of glycine on deep dorsal horn cell activity and receptive fields over postnatal development and the influence of the maturation of spinal glycinergic inhibition upon neonatal pain processing. Nociception and pain behaviour is also powerfully controlled at the level of the spinal cord by descending activity from brainstem nuclei, particularly the rostroventral medulla (RVM) and periaqueductal grey (PAG). In the adult, a background, descending tonic inhibition normally dampens acute nociceptive input but this can shift to facilitation under conditions of persistent or chronic pain (Heinricher and Lumb, 2008). This brainstem axis is the major site of action of the analgesic actions of opioids. We have recently discovered that the descending RVM control of spinal sensory circuits undergoes a remarkable maturational switch over postnatal development (Hathway et al. 2009). Both lesioning and electrical stimulation of RVM at different postnatal ages reveal that RVM control switches from being entirely facilitatory before 3 weeks of age to predominantly inhibitory by 4 weeks. The effect is observed upon both spinal nociceptive reflexes and dorsal horn neuronal activity over this critical developmental period and is likely to be of considerable importance for the maturation sensory transmission and integration. Here we will present new data that establishes a critical period for this switch in descending control and shows that endogenous opioid activity is essential for its normal maturation.