Improving the measurement and treatment of infant pain

Infants undergo numerous medically necessary painful procedures while in hospital, and this early life pain can lead to adverse effects. A range of pain relief interventions are available for use in neonatal units, including pharmacological analgesics, and non- pharmacological comfort measures. However, the literature regarding the efficacy of many of these pain relief interventions is inconclusive and inconsistent, and infant pain is consequently undertreated. To assess infant pain, behavioural and physiological surrogate measures are utilised in the absence of verbal report. However, as these measures are not direct measures of pain, and can be influenced by other factors such as procedure-related distress, their use can lead to inconsistent conclusions regarding the efficacy of pain relief interventions. The perception of pain manifests in the brain, therefore it is plausible that measures of brain activity can provide specific and objective indications of the infant pain experience, and that these measures can be used to assess the efficacy of pain relief interventions. In this thesis, noxious-evoked brain activity is measured and used to investigate the effect of a pharmacological analgesic, paracetamol, and a non- pharmacological pain relief intervention, gentle touch targeted towards C-tactile (CT) fibres. Noxious-evoked brain activity has been well characterised following medically required heel lances and experimental noxious stimuli, but brain activity evoked by alternative clinically relevant stimuli must also be characterised to assess the efficacy of a wider range of pain relief interventions for these procedures. In this thesis, brain activity evoked by immunisation is characterised, enabling the analgesic efficacy of paracetamol to be tested during routine infant immunisations. Between-subject comparisons are often necessary when investigating the efficacy of pain relief interventions for medical procedures. However, there is great individual variability in nociceptive sensitivity, and controlling for this variability could enable better between-group comparisons. In the last section of this thesis, infant nociceptive sensitivity is measured and accounted for, in order to explore how this approach can be used to assess intervention efficacy, using the example of gentle touch targeted towards CT fibres. Overall, the aims of the research described in this thesis are to advance knowledge regarding how infants respond to noxious clinical procedures, how pain relief interventions can modulate these responses, and how individual variability can be accounted for to enable better assessment of intervention efficacy. Research in the area of infant pain management is critical to inform clinical practise and improve the treatment of infant pain.