Pain processing in infants and children is not well understood. As recently as 20 years ago, major surgery was performed on neonates without the use of anesthetics. This is distressing because neonates have lower pain thresholds than adults and early painful experiences influence later pain responses. For example, boys who have been circumcised without anesthetics demonstrate significantly greater pain responses to immunization injections than do boys circumcised with the use of anesthetics. This amplification of pain responses is termed central sensitization and involves 'rewiring' of the nervous system. We propose that the developmental regulation of signal transduction protein kinase C isozymes and neuromodulatory astrocytes within the spinal cord predispose infants to develop central sensitization and that this manifests as increased pain sensitivity. Postnatal rats provide a model for studying the developmental regulation of pain. Postnatal rat pups have been shown to be more sensitive than adults to hind paw application of formalin (an irritant) that produces quantifiable short-term pain behaviors (paw licks and flinches). The present work will study pain processing in the neonatal central nervous systems at the behavioral, electrophysiological, cellular and molecular levels. We will examine the contribution of protein kinase C isozymes and astrocytes to the developmental regulation of formalin-induced central sensitization. The long-term goal is to provide therapeutic targets for the rational discovery and application of non-opioid analgesics in children.
