The spinal neuronal circuitry that subserves nociception and nerve injury is composed of three parts: intrinsic spinal neurons that are either local circuit neurons or projection neurons, the terminals of primary afferent neurons that carry inputs from the periphery, and axon terminals that descend to the spinal cord from the brain. Activity in these circuits is the basis for modulation of the neuronal output from the spinal cord. This project uses a variety of cellular and molecular techniques to study changes in gener expression in animal models of pain and nerve injury. Dynorphin, an opioid peptide that plays an important role in the spinal neural circuitry that subserves nociception, is thought to be involved in enhanced excitability at NMDA receptor sites leading to dorsal horn excitability and resultant altered neural circuits. These changes may form the basis for persistent pain problems. Following noxious stimulation of the periphery, there is a dramatic induction in dynorphin mRNA that can be localized in individual neurons using in situ hybridization histochemistry or quantified using RNA blot analysis. These changes in dynorphin mRNA expression as an indicator of activity in spinal pain pathways to provide insights into the basic mechanismsa that are part of the initial and persistent response to noxious stimulation. Applicaiton of these methods to gender difference in pain responsiveness suggests that spinal cord dynorphin expression and behavioral hyperalgesia may provide an explanation for the link between pain responses and steroid hormones. Similar approaches demonstrate a dramatic alteration in spinal pain pathways after neonatal persistent pain which may result in differences in the response to painful stimuli in the adult. Parallel studies are evaluating the role of transcription factors in the neuronal response to pain and nerve injury and provide evidence that STAT proteins may play a role in the neuronal plasticity that occurs following painful sensory input.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000288-19
Application #
6104582
Study Section
Special Emphasis Panel (PNMB)
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
1998
Total Cost
Indirect Cost
Name
National Institute of Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code