Tissue damage and nerve injury are often associated with inflammation. The common signs of inflammation include hyperalgesia, redness, swelling, and increased temperature. The overall goal of our research program is to determine the mechanisms responsible for the development and maintenance of primary hyperalgesia. The specific goals of this proposal are to (1) identify which peripheral afferents contribute to zymosan-induced mechanical and thermal hyperalgesia using single fiber recordings of low threshold mechanoreceptors (LTMs), high threshold mechanoreceptors (HTMs), A-mechanoheat nociceptors (AMHs), C-polymodal nociceptors (CPMs), and C-mechanonociceptors (CMNs), (2) determine how mechanical and thermal stimulus-response functions (SRFs) of nociceptive specific (NS) and wide dynamic range (WDR) spinal dorsal horn neurons are affected under conditions of zymosan-induced inflammation, (3) determine whether spinal administration of selective glutamate receptor antagonists differentially affect the altered stimulus-response characteristics of NS and WDR neurons to thermal and mechanical stimuli under conditions of zymosan-induced inflammation, and (4) determine whether zymosan-induced inflammation results in hyperexcitability of NS and WDR spinal dorsal horn neurons and if so, whether it can be sustained in the presence of glutamate receptor antagonists that block primary hyperalgesia to thermal and mechanical stimuli. These goals will be accomplished in electrophysiological and pharmacological studies of primary hyperalgesia in the rat. Intraplantar administration of the inflammatory agent zymosan will be used to produce primary hyperalgesia to thermal and mechanical stimuli. In each aim, complete SRFs to thermal (36 C - 50 C in 2 C increments) and mechanical stimuli (0.02 - 190 g) will be generated before and at hourly intervals following administration of zymosan. All units will be studied using a repeated measures design. These studies will advance our understanding of the mechanisms of thermal and mechanical primary hyperalgesia resulting from inflammation. Data obtained from the pharmacological studies will help resolve some of the current controversy over whether similar or different excitatory amino acids (EAAs) mediate the production and/or maintenance of mechanical and thermal hyperalgesia.
| Turnbach, Meredith E; Spraggins, D Seth; Randich, Alan (2002) Spinal administration of prostaglandin E(2) or prostaglandin F(2alpha) primarily produces mechanical hyperalgesia that is mediated by nociceptive specific spinal dorsal horn neurons. Pain 97:33-45 |
| Turnbach, Meredith E; Randich, Alan (2002) The role of spinal neurokinin-1 and glutamate receptors in hyperalgesia and allodynia induced by prostaglandin E(2) or zymosan in the rat. Pain 97:127-37 |
