? The goal of this revised application is to obtain support for the applicant such that he can focus his full time efforts on his research career and be released from his heavy teaching load. There are three major scientific aims of the research described in this application. The first major aim focuses on the basic biological mechanisms that underlie opiate tolerance and withdrawal in the infant and how those mechanisms differ with age. Although opiates continue to be the most important clinical tool available to treat pain in the infant patient, opiates also produce significant adverse effects including dependence and tolerance. The mechanisms of tolerance and dependence are different in the infant and the adult, making putative treatments for the adult inappropriate for the infant.
The second aim defines the developmental changes in the opioid and non-opioid mechanisms of nociception and antinociception. One of the limitations in the treatment of the seriously ill infant patient has been the limited understanding of how pain processing differs in the infant from the adult. Here we seek to understand the basic biological mechanisms that mediate nociception and antinociception in the infant and define how those mechanisms change over the course of development. Third, we characterize changes of sensory function and gene expression in the spinal cord after injury and after transplants of either fetal tissue or genetically modified cells that rescue function after that injury. Increased pain sensitivity, either as allodynia or hyperalgesia, is a serious and common consequence of spinal cord injury. Promising repair strategies that include transplants that secrete various growth factors may encourage increased peripheral input and enhanced pain even with improved motor function. Therefore we propose to assess changes in sensitivity to sensory stimuli following injury and treatment to determine whether or not treatments that promote repair and motor recovery also modify sensitivity to peripheral stimulation. In the studies described in this application, we propose a multidimensional approach, including behavioral, pharmacologic, anatomic and genetic methods. Many of these approaches were introduced into the applicant' s lab during the prior K02 support. Continuation of the K02 award, by reducing the PI's substantial teaching and administrative commitments, will allow him the resources to continue these studies, further his mentoring efforts, maintain his increased productivity, and continue his efforts to become involved in science policy and advocacy at the national and international levels. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research (K02)
Project #
2K02DA000325-06A1
Application #
6610768
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Thadani, Pushpa
Project Start
1997-04-10
Project End
2008-03-31
Budget Start
2003-06-25
Budget End
2004-03-31
Support Year
6
Fiscal Year
2003
Total Cost
$122,472
Indirect Cost
Name
Hunter College
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
620127915
City
New York
State
NY
Country
United States
Zip Code
10065
Hunter, Deirtra; Chai, Christina; Barr, Gordon A (2015) Effects of COX inhibition and LPS on formalin induced pain in the infant rat. Dev Neurobiol 75:1068-79
Barr, G A; Wang, S (2013) Analgesia induced by localized injection of opiate peptides into the brain of infant rats. Eur J Pain 17:676-91
Chan, Thomas; Kyere, Kwaku; Davis, Brian R et al. (2011) The role of the medial prefrontal cortex in innate fear regulation in infants, juveniles, and adolescents. J Neurosci 31:4991-9
Barr, Gordon A; McPhie-Lalmansingh, Anika; Perez, Jessica et al. (2011) Changing mechanisms of opiate tolerance and withdrawal during early development: animal models of the human experience. ILAR J 52:329-41
Hunter, Deirtra A; Barr, Gordon A; Amador, Nicole et al. (2011) Estradiol-induced antinociceptive responses on formalin-induced nociception are independent of COX and HPA activation. Synapse 65:643-51
Hunter, Deirtra A; Barr, Gordon A; Shivers, Kai-Yvonne et al. (2011) Interactions of estradiol and NSAIDS on carrageenan-induced hyperalgesia. Brain Res 1382:181-8
Barr, Gordon A (2011) Formalin-induced c-fos expression in the brain of infant rats. J Pain 12:263-71
Barr, Gordon A; Moriceau, Stephanie; Shionoya, Kiseko et al. (2009) Transitions in infant learning are modulated by dopamine in the amygdala. Nat Neurosci 12:1367-9
Barr, Gordon A; Gao, Puhong; Wang, Shaoning et al. (2005) Microarray analysis of gene expression following the formalin test in the infant rat. Pain 117:6-18
Zhu, H; Barr, G A (2001) Inhibition of morphine withdrawal by the NMDA receptor antagonist MK-801 in rat is age-dependent. Synapse 40:282-93

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