? 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 primary afferent nerve terminal. Neurophysiologic, biochemical, and molecular approaches will be used in concert to examine the mechanisms that contribute to activation and sensitization of nociceptive afferent fibers and subsequent primary hyperalgesia. Our working hypothesis is that 1) nociceptors responding to heat develop background activity and heat sensitization after incision. This sensitization is caused by H+ ions and NGF increased by the incision acting on VR1 receptors contributing to heat hyperalgesia and nonevoked pain behaviors. VR1 activation does not influence behaviors indicating mechanical hyperalgesia. 2) MIAs are activated by incision and develop mechanosensitivity. H+ ions and lactate increased by incision activate ASIC channels contributing to mechanical hyperalgesia. Incision-induced changes in expression of receptors activated by low pH will be measured. These data will determine the particular afferents sensitized by incision and the role of receptors activated by decreased tissue pH on pain behaviors caused by the incision. The proposed experiments will advance our understanding of postoperative incisional pain and provide a basis for rationale design of new pharmacologic treatment modalities. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM067762-04
Application #
7057770
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Cole, Alison E
Project Start
2003-05-01
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2008-04-30
Support Year
4
Fiscal Year
2006
Total Cost
$285,187
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
Gu, He; Sugiyama, Daisuke; Kang, Sinyoung et al. (2018) Deep Tissue Incision Enhances Spinal Dorsal Horn Neuron Activity During Static Isometric Muscle Contraction in Rats. J Pain :
Kido, Kanta; Gautam, Mamta; Benson, Christopher J et al. (2013) Effect of deep tissue incision on pH responses of afferent fibers and dorsal root ganglia innervating muscle. Anesthesiology 119:1186-97
Kang, Sinyoung; Lee, Dongchul; Theusch, Brett E et al. (2013) Wound hypoxia in deep tissue after incision in rats. Wound Repair Regen 21:730-9
Kang, Sinyoung; Jang, Jun Ho; Price, Margaret P et al. (2012) Simultaneous disruption of mouse ASIC1a, ASIC2 and ASIC3 genes enhances cutaneous mechanosensitivity. PLoS One 7:e35225
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
Xu, Jun; Gu, He; Brennan, Timothy J (2010) Increased sensitivity of group III and group IV afferents from incised muscle in vitro. Pain 151:744-55
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
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

Showing the most recent 10 out of 20 publications