Abstract
1. We developed a simple and sensitive peripheral analgesic test in mice. 2. Substance P (SP) given into the planta (i.pl.) of the mouse hind limb produced a flexor response. The flexor response was dependent on SP doses (0.1-100 pmol, i.pl.). When SP (10 pmol) was given every 5 min, there were stable flexor responses. These nociceptive responses were completely abolished by CP-96,345, a neurokinin 1 receptor antagonist. 3. SP-induced responses were also blocked by several signal transduction-related compounds, such as tetrodotoxin, EGTA, and U73122, a selective phospholipase C inhibitor. 4. These findings suggest that SP depolarizes peripheral nerve endings, possibly through inositol trisphosphate (Ins P3)-gated Ca2+ influx, followed by induction of action potentials in the peripheral axons of primary afferent neurons.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Afferent Pathways / physiology
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Animals
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Biphenyl Compounds / pharmacology
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Egtazic Acid / pharmacology
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Estrenes / pharmacology
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GTP-Binding Proteins / physiology
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Hindlimb / innervation
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Inositol 1,4,5-Trisphosphate / physiology
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Ion Transport
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Male
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Mice
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Mice, Inbred Strains
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Models, Neurological
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Muscle Contraction / drug effects*
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Muscle Contraction / physiology
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Neurons, Afferent / drug effects*
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Neurons, Afferent / physiology
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Neurotoxins / pharmacology
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Nociceptors / drug effects*
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Phosphatidylinositol Diacylglycerol-Lyase
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Phosphodiesterase Inhibitors / pharmacology
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Pyrrolidinones / pharmacology
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Receptors, Neurokinin-1 / drug effects*
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Receptors, Neurokinin-1 / physiology
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Reflex / drug effects
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Signal Transduction / drug effects*
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Signal Transduction / physiology
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Substance P / pharmacology*
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Tetrodotoxin / pharmacology
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Type C Phospholipases / antagonists & inhibitors
Substances
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Biphenyl Compounds
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Estrenes
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Neurotoxins
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Phosphodiesterase Inhibitors
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Pyrrolidinones
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Receptors, Neurokinin-1
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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Substance P
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Tetrodotoxin
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Egtazic Acid
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Inositol 1,4,5-Trisphosphate
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Type C Phospholipases
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GTP-Binding Proteins
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Phosphatidylinositol Diacylglycerol-Lyase
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CP 96345