Postoperative, incisional pain is a unique but common form of acute pain. Since effective postoperative analgesia reduces morbidity following surgery, new treatments continue to be investigated. The proposal is dedicated toward studies of the mechanisms that subserve acute postoperative pain, It is through the study of mechanisms that a better understanding of incisional pain can be achieved and new treatments can be advanced. The work proposed will specifically characterize the mechanisms for incisional pain at the neuronal level in the dorsal horn. Neurochemical and neurophysiological approaches will be used in concert to examine the mechanisms that contribute to the development and maintenance of primary and secondary hyperalgesia after incision. Our working hypothesis is that glutamate and aspartate act on nonNMDA (N-methyl-D-aspartate) receptors to induce changes in spinal cord processing and to maintain the sensitization of dorsal horn neurons. Specifically, we will: (1) Investigate the effect of NMDA, nonNMDA and metabotropic excitatory amino acid receptor antagonists on the response properties of spinal cord dorsal horn neurons sensitized by an incision. (2) Determine the role of NMDA and nonNMDA receptors, including calcium-permeable AMPA (amino-3-hydroxy-5-methylisoxazole-4-propionic acid ) receptors and kainate receptors, on the secondary hyperalgesia caused by an incision of the gastrocnemius region. Neurophysiologic studies will determine the effect of NMDA and nonNMDA receptor antagonists on a specific measure of central sensitization of dorsal horn neurons caused by incision and in so doing reveal the specific contribution of central sensitization to pain behaviors. (3) Confirm that incision results in an increased basal or evoked release of the excitatory amino acids, aspartate and glutamate, in the spinal cord dorsal horn. These studies will use microdialysis to examine the time course and magnitude of glutamate and aspartate release during and after incision under quiescent conditions and conditions of repetitive stimulation. Insights gained into the role of excitatory amino acids, and in particular the role of calcium-permeable AMPA and kainate receptors, will advance our understanding of postoperative incisional pain and provide a basis for rationale design of new pharmacologic treatment

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055831-08
Application #
6684090
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Cole, Alison E
Project Start
1997-05-01
Project End
2005-11-30
Budget Start
2003-12-01
Budget End
2004-11-30
Support Year
8
Fiscal Year
2004
Total Cost
$294,000
Indirect Cost
Name
University of Iowa
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Xu, Jun; Brennan, Timothy J (2011) The pathophysiology of acute pain: animal models. Curr Opin Anaesthesiol 24:508-14
Brennan, Timothy J (2011) Pathophysiology of postoperative pain. Pain 152:S33-40
Kang, Sinyoung; Wu, Chaoran; Banik, Ratan K et al. (2010) Effect of capsaicin treatment on nociceptors in rat glabrous skin one day after plantar incision. Pain 148:128-40
Xu, Jun; Brennan, Timothy J (2010) Guarding pain and spontaneous activity of nociceptors after skin versus skin plus deep tissue incision. Anesthesiology 112:153-64
Wu, Chaoran; Erickson, Mark A; Xu, Jun et al. (2009) Expression profile of nerve growth factor after muscle incision in the rat. Anesthesiology 110:140-9
Kang, Sinyoung; Brennan, Timothy J (2009) Chemosensitivity and mechanosensitivity of nociceptors from incised rat hindpaw skin. Anesthesiology 111:155-64
Spofford, Christina M; Ashmawi, Hazem; Subieta, Alberto et al. (2009) Ketoprofen produces modality-specific inhibition of pain behaviors in rats after plantar incision. Anesth Analg 109:1992-9
Xu, Jun; Brennan, Timothy J (2009) Comparison of skin incision vs. skin plus deep tissue incision on ongoing pain and spontaneous activity in dorsal horn neurons. Pain 144:329-39
Xu, Jun; Richebe, Philippe; Brennan, Timothy J (2009) Separate groups of dorsal horn neurons transmit spontaneous activity and mechanosensitivity one day after plantar incision. Eur J Pain 13:820-8
Banik, Ratan K; Brennan, Timothy J (2009) Trpv1 mediates spontaneous firing and heat sensitization of cutaneous primary afferents after plantar incision. Pain 141:41-51

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