Pain management is a general concern for healthcare quality in terms of analgesic drugs prescription. In the particular context of neonatal intensive care, it’s well known that an efficient pain management will decrease mortality and morbidity of newborns. Therefore, concerns about short- and long-term adverse consequences of early pain exposure in newborn infants imply to develop valid and reliable measures of infant pain. Indeed, the plasticity of developing brain is vulnerable to pain and/or stress, that in turn may cause long term neurodevelopmental changes, including altered pain sensitivity and neuroanatomic and behavioural abnormalities. During neonatal intensive care stay, large number of painful procedures are performed, the majority of which are not accompanied by adequate analgesia. Optimal management requires competent pain assessment which can be especially difficult to perform in this non verbal population. Various pain assessment scales has been developed, mainly based on both behavioural and physiological indicators of pain. These scoring systems allow bedside evaluation and help decision taking for managing pain. However, those different pain scales have some limitations: • reliability has been questioned even when performed by well-trained nurses, in particular in distinguishing pain and discomfort; • some pain scales require prolonged clinical observation of the infants, especially for assessing prolonged pain; • pain scoring is intermittent, with a risk to not take into account some painful episodes during the inter-rating period. We have developed an instantaneous heart rate variability (HRV) analysis method, non intrusive and user-friendly, based on the ECG signal acquisition. This analysis method enabled us to design parameters related to the influence of pain on the Autonomic Nervous System (ANS) activity. Validated for adults under general anesthesia, this method is the subject of 2 international patents. After two preliminary studies realized in the neonatal intensive care unit, this project intended to adapt this technology for the particular application of the monitoring of pain and/or comfort of newborns.