Ontogeny of spinal glutamate receptors in nociception

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DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award (K01) application proposes a program of research and training to extend the candidate's behavioral neuroscience training to strengthen molecular and neural aspects of behavioral regulation. The program will accomplish the following goals: 1) strengthen and deepen the candidate's neuropharmacological and neuroanatomical skills gained at the Division of Developmental Psychobiology of Columbia University; 2) provide training in molecular biological and electrophysiological concepts and techniques in collaboration with specialized laboratories at Columbia University; 3) apply these skills to investigate the development of nociceptive systems in the infant animal. The specific research aim of the proposed study is to investigate the role of spinal ionotropic NMDA and AMPA glutamate receptors in acute pain and hyperalgesia across early ontogeny in the rat. This will be done by: 1) using pharmacological methods to determine the role of spinal NMDA and AMPA receptors in nociception during the first 3 weeks after birth; 2) using in situ and immunocytochemistry to determine the impact of exposure to acute pain and inflammatory-induced hyperalgesia on spinal NMDA and AMPA receptors across development; 3) using electrophysiological methods to determine whether NMDA and AMPA recpetors play a role in inflammatory-induced injury on spinal neurons across development. Knowledge of the impact of exposure to nociceptive stimuli on these receptors is important in developing pain management techniques that reduce pain during injury and potentially block long-term changes in the nociceptive system caused by the early injury. The proposed training program is critical in the candidates transition from a postdoctoral fellow to an - independent investigator by providing conceptual and technical skills to investigate the development of nociceptive systems.