The proposal is for continuation of work on the organization of the mammalian spinothalamic tract (STT) and its descending control. The emphasis will be on plastic changes in responsiveness of these neurons following tissue or nerve injury. Such changes may be causally related to the primary and secondary hyperalgesia and allodynia that follows such injuries in humans. Recordings will be made from STT cells in anesthetized monkeys before and after intradermal injection of capsaicin or induction of acute arthritis and in anesthetized rats after peripheral neuropathy or dorsal rhizotomies. It is hypothesized that central sensitization of STT cells will develop in these animal models. This central sensitization will be counteracted by administration of agents that either interfere with the development of sensitization, such as excitatory amino acid (EAA) and substance P (SP) antagonists, or by specific agonists of neurotransmitters that may be released by activation of descending inhibitory pathways. Iontophoretic co-application of EAAs and SP (or possibly other peptides) is suggested to cause central sensitization by activation of second messenger systems. The latter idea will be tested by administration of trans-ACPD, a metabotropic glutamate receptor agonist. The goal is to improve our understanding of the mechanisms of hyperalgesia so that improved drug therapies can be developed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS009743-25
Application #
2261664
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1975-05-01
Project End
1996-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
25
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Zoology
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Willis Jr, William D (2009) The role of TRPV1 receptors in pain evoked by noxious thermal and chemical stimuli. Exp Brain Res 196:5-11
Sun, R; Yan, J; Willis, W D (2007) Activation of protein kinase B/Akt in the periphery contributes to pain behavior induced by capsaicin in rats. Neuroscience 144:286-94
Saab, C Y; Willis, W D (2002) Cerebellar stimulation modulates the intensity of a visceral nociceptive reflex in the rat. Exp Brain Res 146:117-21
Saab, C Y; Willis, W D (2001) Nociceptive visceral stimulation modulates the activity of cerebellar Purkinje cells. Exp Brain Res 140:122-6
Willis Jr, W D (1999) Dorsal root potentials and dorsal root reflexes: a double-edged sword. Exp Brain Res 124:395-421
Wu, J; Lin, Q; Lu, Y et al. (1998) Changes in nitric oxide synthase isoforms in the spinal cord of rat following induction of chronic arthritis. Exp Brain Res 118:457-65
Tsuruoka, M; Willis, W D (1998) Involvement of the locus coeruleus in analgesic effects of a low dose of naloxone during the inflammatory process. Exp Brain Res 119:166-70
Peng, Y B; Lin, Q; Willis, W D (1997) Involvement of protein kinase C in responses of rat dorsal horn neurons to mechanical stimuli and periaqueductal gray descending inhibition. Exp Brain Res 114:561-70
Lin, Q; Peng, Y; Willis, W D (1994) Glycine and GABAA antagonists reduce the inhibition of primate spinothalamic tract neurons produced by stimulation in periaqueductal gray. Brain Res 654:286-302
Rees, H; Sluka, K A; Westlund, K N et al. (1994) Do dorsal root reflexes augment peripheral inflammation? Neuroreport 5:821-4

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