Inhibitors of G-proteins and protein kinases reduce the sensitization to mechanical stimulation and the desensitization to heat of spinothalamic tract neurons induced by intradermal injection of capsaicin in the primate

K A Sluka; H Rees; P S Chen; M Tsuruoka; W D Willis

doi:10.1007/PL00005675

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Inhibitors of G-proteins and protein kinases reduce the sensitization to mechanical stimulation and the desensitization to heat of spinothalamic tract neurons induced by intradermal injection of capsaicin in the primate

Journal article

Peer reviewed

Inhibitors of G-proteins and protein kinases reduce the sensitization to mechanical stimulation and the desensitization to heat of spinothalamic tract neurons induced by intradermal injection of capsaicin in the primate

K A Sluka, H Rees, P S Chen, M Tsuruoka and W D Willis

Experimental brain research, Vol.115(1), pp.15-24

06/1997

DOI: 10.1007/PL00005675

PMID: 9224830

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Abstract

Intradermal injection of capsaicin results in sensitization of spinothalamic tract cells to brushing and pressure applied to the cutaneous receptive field in anesthetized monkeys. A significant increase in background activity also occurs immediately after capsaicin injection that lasts for at least 2 h. A 40-50% decrease in the response to noxious heat stimuli is also observed following capsaicin injection. This study investigated the spinal role of second messengers by extracellularly recording from spinothalamic tract cells and delivering inhibitors of second messenger pathways to the spinal cord by microdialysis. Blockade of protein kinases with the general protein kinase inhibitor, H7 (5.0 mM, n = 6), reduced the sensitization of the cells to brush and pressure. Blockade of protein kinase C with NPC15437 (10.0 mM, n = 10) reduced the increased background activity and the increased responses to brush. Blockade of protein kinase A with H89 (0.01 mM, n = 9) was most effective. H89 reduced the background activity, the increased responses to brush and press, and reversed the decreased response to noxious heat stimuli. Blockade of G-proteins with the general G-protein inhibitor, GDP-beta-S (1.0 mM, n = 9), reduced the background activity and the responses to brush and pressure without affecting the decreased response to heat. Thus, multiple intracellular messengers appear to be involved in the processing of central sensitization induced by activation of C-fibers following intradermal injection of capsaicin.

Guanosine 5'-O-(3-Thiotriphosphate) - pharmacology

Neural Pathways - drug effects

Spinal Cord - drug effects

Capsaicin - pharmacology

GTP-Binding Proteins - antagonists & inhibitors

Neural Pathways - physiology

Capsaicin - administration & dosage

Isoquinolines - pharmacology

Nerve Fibers - physiology

Piperidines - pharmacology

Thalamus - physiology

Spinal Cord - cytology

Injections, Intradermal

Physical Stimulation

Enzyme Inhibitors - pharmacology

Nerve Fibers - drug effects

Hot Temperature

Thionucleotides - pharmacology

Thalamus - drug effects

Guanosine 5'-O-(3-Thiotriphosphate) - analogs & derivatives

Adenosine Diphosphate - pharmacology

Haplorhini

Protein Kinase Inhibitors

Animals

Microdialysis

Sulfonamides

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology

Spinal Cord - physiology

Neural Pathways - cytology

Thalamus - cytology

Capsaicin - antagonists & inhibitors

Adenosine Diphosphate - analogs & derivatives

Details

Title: Subtitle: Inhibitors of G-proteins and protein kinases reduce the sensitization to mechanical stimulation and the desensitization to heat of spinothalamic tract neurons induced by intradermal injection of capsaicin in the primate
Creators: K A Sluka - Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555-1069, USA
H Rees
P S Chen
M Tsuruoka
W D Willis
Resource Type: Journal article
Publication Details: Experimental brain research, Vol.115(1), pp.15-24
Publisher: Germany
DOI: 10.1007/PL00005675
PMID: 9224830
ISSN: 0014-4819
eISSN: 1432-1106
Language: English
Date published: 06/1997
Academic Unit: Iowa Neuroscience Institute; Nursing; Physical Therapy and Rehabilitation Science; Neuroscience and Pharmacology
Record Identifier: 9984040483102771

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