Abstract
We investigated the effects of inhibiting spinal protein kinases including PKC, PKA and PKG on tactile allodynia in rats with a unilateral tight ligation on L5/L6 spinal nerves (Chung model). The intrathecal (IT) delivery of GF109203X, a PKC inhibitor, produced a potent and long lasting anti-allodynic effect. The effect was dose-dependent and stereospecific. Bisindolymaleimide V, an inactive homologue of GF, had no effect. Additionally, two other PKC inhibitors, PKC19-31 and chelerythrine, displayed significant anti-allodynic action. Spinal PKA, but not PKG, is likely involved in Chung tactile allodynia, since H89 (a PKA inhibitor) showed anti-allodynic activity, while KT5823 (a PKG inhibitor) had only a minor effect. These data emphasize that spinal PKC plays an important role in nerve injury-induced tactile allodynia. Other protein kinases such as PKA may also contribute to this phenomenon.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors*
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Cyclic AMP-Dependent Protein Kinases / physiology
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Cyclic GMP-Dependent Protein Kinases
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use*
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Indoles / pharmacology
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Indoles / therapeutic use*
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Injections, Spinal
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Ligation
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Male
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Maleimides / pharmacology
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Maleimides / therapeutic use*
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Pain / drug therapy*
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Protein Kinase C / antagonists & inhibitors*
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Protein Kinase C / physiology
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Protein Kinase Inhibitors*
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Protein Kinases / physiology
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Rats
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Rats, Sprague-Dawley
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Spinal Nerves / drug effects
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Spinal Nerves / injuries
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Spinal Nerves / physiology
Substances
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Enzyme Inhibitors
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Indoles
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Maleimides
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Protein Kinase Inhibitors
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Protein Kinases
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Cyclic AMP-Dependent Protein Kinases
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Cyclic GMP-Dependent Protein Kinases
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Protein Kinase C
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bisindolylmaleimide I