Inhibition of spinal protein kinase C reduces nerve injury-induced tactile allodynia in neuropathic rats.
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.
Hua
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Department of Anesthesiology, University of California, San Diego, La Jolla 92093-0818, USA. xyhua@ucsd.edu
Chen
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Yaksh
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D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D008301:Maleimides / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects / Q000293:injuries / Q000502:physiology
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; C070515:bisindolylmaleimide I