Inhibition of spinal protein kinase C reduces nerve injury-induced tactile allodynia in neuropathic rats.

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.

• Authors: X Y Hua, P Chen, T L Yaksh
• Journal: Neuroscience letters (Neurosci Lett) Vol. 276 Issue 2 Pg. 99-102 (Dec 03 1999) ISSN: 0304-3940 [Print] Ireland
• PMID: 10624801 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Enzyme Inhibitors
• Indoles
• Maleimides
• Protein Kinase Inhibitors
• Protein Kinases
• Cyclic AMP-Dependent Protein Kinases
• Cyclic GMP-Dependent Protein Kinases
• Protein Kinase C
• bisindolylmaleimide I

Topics

• Animals
• Cyclic AMP-Dependent Protein Kinases (antagonists & inhibitors, physiology)
• Cyclic GMP-Dependent Protein Kinases
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Indoles (pharmacology, therapeutic use)
• Injections, Spinal
• Ligation
• Male
• Maleimides (pharmacology, therapeutic use)
• Pain (drug therapy)
• Protein Kinase C (antagonists & inhibitors, physiology)
• Protein Kinase Inhibitors
• Protein Kinases (physiology)
• Rats
• Rats, Sprague-Dawley
• Spinal Nerves (drug effects, injuries, physiology)