"We begin by considering the scientific evidence for the presence of specific anatomical and physiological connections in the brain that are responsible for signalling noxious events to the central nervous system. Noxious stimuli are those that damage the tissues of the body or threaten to do so, such as surgical incision or physical trauma of the skin. In this context, we define pain as ‘the unpleasant sensory or emotional response to such tissue damage’ and trace the development of those responses through fetal development. We follow the path of the signals produced by tissue damage at sensory detectors in the skin and other organs, through to sensory circuits in the spinal cord, brainstem and thalamus and finally to the cerebral cortex, the site of higher level sensory processing. At each stage, we consider the scientific evidence for functional development and how this evidence may be interpreted. This section includes details derived from over 50 papers identified as relevant. Most were published since the last Working Party report1 but this current report also considers the older material included in the previous report. In addition to understanding the anatomical and physiological connections, it is also important to consider the psychological aspects of pain. Broadly accepted definitions of pain refer to pain as a subjective experience involving cognition, sensation and affective processes. These psychological concepts are inevitably harder to address in a fetus but should not be ignored."