One of the difficulties in developing treatments for the seriously ill infant patient has been the limited understanding of how pain processing differs between the infant and the adult. In particular, there are developmental differences in how pain is processed, and in the long-term consequences of tissue insult. Growing evidence both from the clinic and the laboratory demonstrate that there are long lasting changes in sensitivity to subsequent noxious stimuli following injury in the infant. Further, there appears to be a """"""""critical"""""""" period, at least in the rat, such than injury in the first two weeks of life, but not later, results in those long lasting changes in pain sensitivity. This clearly has very important clinical implications; yet nothing is known of the mechanisms engaged by the experience of pain in early development. The recent development of microarray methods to assess simultaneously changes in the expression in thousands of genes provides a unique opportunity to define the neural and genetic changes that might be responsible for the differences in pain processing in infants, immediately and in the 24 hours after injury, and into adulthood. Here we propose to use well-characterized oligonucleotide microarrays (Affymetrix) and state of the art analytic methods to define those alterations in gene expression induced by injury. We assay the dorsal horn of the lumbar enlargement of the spinal cord as a model system, largely because of described short and long terms changes in spinal cord function and neurobiology induced by injury. We test rat pups at 3 and 21 days of age and assess gene expression changes at four times after insult over 24 hours. This describes the more immediate changes in gene expression as a function of injury. The second series of studies examine changes in gene expression in the adult spinal cord in pups injured at different ages in early in development. In the putative critical period, during the first two weeks of life, pups are injected with carrageenan. Older pups are tested because they are outside the critical period. Adults treated as pups are tested again, with or without insult, and gene expression is assayed by microarray. The results of these experiments will define in detail, changes in gene expression that are induced by injury early in development when nociceptive processes are distinctly different than the adult, and again later in development, after the end of the critical period. Further, we describe long-term changes in expression that might explain the """"""""permanent"""""""" changes in pain perception induced by early injury. These data will provide the basis of rational treatments that might reduce any deleterious effects of pain experience by premature and seriously ill infants.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS047159-01A1
Application #
6824266
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Porter, Linda L
Project Start
2004-07-01
Project End
2008-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$224,267
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
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