Abstract

In this proposal we plan to continue examining the role of serotonin (5-hydroxytryptamine, 5-HT) in the descending control of medullary and spinal dorsal horn neurons. An isolated (in vitro) brainstem - spinal cord preparation of the frog will be used as a model to study the mechanism(s) by which 5-HT might act as a transmitter or modulator in the dorsal horn. Intracellular recordings will be attempted in order to examine the effects of 5- HT on the resting and dorsal root-evoked membrane potential and input resistance of the dorsal horn neurons. An estimate of the reversal potential and ionic dependence of the 5-HT produced effects is also attempted, as will an examination of the effects of 5-HT antagonists, synaptic transmission blockade, and interaction with other putative transmitters (e.g., glutamate). Subsequently, an attempt will be made to correlate the 5-HT-induced effects with those produced by electrical stimulation of brainstem sites giving rise to the descending 5-HT pathways in order to determine whether the two act through identical mechanisms (i.e., whether 5-HT meets the """"""""identity of action"""""""" criterion). Additionally, the effects of both 5-HT application and brainstem stimulation will be examined to determine whether they modify a ventral root potential that might be an index of nociceptive behavior. Finally, the effects of norepinephrine will be examined in precisely the same way as for 5-HT. The proposal should increase our knowledge of nociception at medullary and spinal levels, and this knowledge might lead to significant advances in dental and cutaneous pain management.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS021278-04A1
Application #
3402240
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1984-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Hegg, C C; Miletic, V (1996) Acute exposure to inorganic lead modifies high-threshold voltage-gated calcium currents in rat PC12 cells. Brain Res 738:333-6
Backonja, M M; Miletic, G; Miletic, V (1995) The effect of continuous morphine analgesia on chronic thermal hyperalgesia due to sciatic constriction injury in rats. Neurosci Lett 196:61-4
Backonja, M; Wang, B; Miletic, V (1994) Responses of neurons in the ventrolateral orbital cortex to noxious cutaneous stimulation in a rat model of peripheral mononeuropathy. Brain Res 639:337-40
Lu, G W; Hoffert, M J; Miletic, V (1993) Spontaneous activity of cat spinal ganglion neurons in vivo. Brain Res Bull 31:523-30
Miletic, V; Lu, G W (1993) Characteristics of action potentials recorded from cat spinal ganglion neurons in vivo. Brain Res Bull 31:531-8
Tan, H; Miletic, V (1992) Diverse actions of 5-hydroxytryptamine on frog spinal dorsal horn neurons in vitro. Neuroscience 49:913-23
Tan, H J; Miletic, V (1990) Bulbospinal serotoninergic pathways in the frog Rana pipiens. J Comp Neurol 292:291-302
Lu, G W; Miletic, V (1990) Responses of type A cat spinal ganglion neurons to repetitive stimulation of their central and peripheral processes. Neuroscience 39:259-70
Tan, H J; Miletic, V (1990) Electrophysiological properties of frog spinal dorsal horn neurons and their responses to serotonin: an intracellular study in the isolated hemisected spinal cord. Brain Res 528:344-8
Miletic, V; Coffield, J A (1989) Responses of neurons in the rat nucleus submedius to noxious and innocuous mechanical cutaneous stimulation. Somatosens Mot Res 6:567-87

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