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Despite the high burden of pain experienced by hospitalised neonates, there are few analgesics with proven efficacy. In part, this is due to the lack of a gold standard to measure pain in neonates. Assessing a complex experience like pain is challenging and, in the absence of self-report, all indicators of pain are surrogate measures. Clinicians often rely on behavioural and autonomic physiological responses which can be subjective and have limited sensitivity and specificity to detect pain. The pain experience requires the nociceptive signal to be processed in the brain. From a very young age, infants have the basic neural functional connectivity for pain perception. Thus, brain activity may provide a quantitative and objective measure of nociceptive processing in the infant brain. Noxious-evoked brain activity using electroencephalography (EEG) has been previously characterised following experimental noxious stimuli and heel lances. In this thesis, I assessed the generalisability of a brain-derived surrogate measure of pain across various body locations and stimulus modalities. The morphology and latency of the evoked potentials were characterised following clinically-required injections applied to the thigh, and the efficacy of paracetamol during routine immunisations was evaluated in a pilot study. The magnitude of the brain activity response to the same stimulus intensity can be highly variable between infants. As a result, large sample sizes are often required in studies of analgesic efficacy to account for inter-individual variability. In the second study, I developed an EEG-based paradigm that can be used to determine the baseline sensitivity of individual infants to noxious stimuli and I demonstrated that this paradigm can help to reduce sample sizes in analgesic clinical trials in infants. The normal development of the nervous system is vulnerable to alterations by multiple factors, with the potential for long-term structural and functional detrimental outcomes. Immune function and sensitivity to pain are closely related, but the impact of early life inflammation on sensory nervous system development is poorly understood. In the final study, I used electrophysiological measures to investigate this relationship. I demonstrated in a cohort of term neonates that inflammation is associated with increased spinal cord excitability and hyperalgesia. In summary, this thesis advances our understanding of the processing of nociceptive information in the infant brain and demonstrates how the use of brain-derived measures of pain can improve the evaluation of analgesic interventions.