Tissue damage as the result of injury or disease produces local inflammation and uncharacteristically painful sensations to noxious stimuli, termed hyperalgesia. A central component of hyperalgesia, central sensitization, is an increase in the excitability of spinal neurons following injury. The long term goal of this project is to gain a better understanding of the central neural mechanisms involved in hyperalgesia such that better therapeutic manipulations and treatments can be designed to alleviate excessive pain post-injury and prevent pain and discomfort that are a consequence of surgery. Activation of C-fiber primary afferents is a necessary prerequisite of central sensitization, suggesting that neuropeptides may play a role in the induction of central sensitization and/or acute nociceptive transmission. A multidisciplinary approach will be used to address the three specific aims of this application: 1) To determine the role of neuropeptides in acute nociceptive transmission from non-inflamed tissue. 2) To determine the role of neuropeptides in acute nociceptive transmission following inflammation. 3) To determine the role of neuropeptides in the induction of central sensitization of dorsal horn neurons following injury. Behavioral, electrophysiological and immunocytochemical methodologies will be used to examine the role of neuropeptides in acute nociceptive transmission from somatic tissue. These experiments will test the following hypotheses: a) neuropeptides are involved in the acute nociceptive transmission of specific stimulus modalities; b) a neuropeptide that signals a stimulus modality from non-inflamed tissue will signal that same modality following inflammation; and c) the same neuropeptide(s) induce central sensitization as a result of inflammation regardless of the injured tissue and that these neuropeptides are not involved in acute nociceptive transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS030604-02
Application #
2268573
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1993-07-01
Project End
1997-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Iowa
Department
Pharmacology
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242