Peripheral involvement of PKA and PKC in subcutaneous bee venom-induced persistent nociception, mechanical hyperalgesia, and inflammation in rats.

Abstract

The roles of central protein kinases A and C (PKA and PKC) in various pain states have intensively been investigated during the past decade. The aim of the present study was to investigate the peripheral involvement of PKA and PKC in persistent nociceptive response, evoked pain behaviors, and inflammation induced by subcutaneous (s.c.) injection of bee venom (BV, 0.2mg/50 microl) in rats. The effects of intraplantar injection of H-89 (a PKA inhibitor, 5-100 microg/50 microl) and chelerythrine chloride (a PKC inhibitor, 5-100 microg/50 microl) on BV-elicited persistent nociception (nociceptive flinching reflex), mechanical hyperalgesia, and inflammation were systematically investigated. Pre-treatment with H-89 dose-dependently inhibited only BV-induced mechanical hyperalgesia, but not the persistent nociception and inflammation. In contrast, pre-treatment with chelerythrine chloride dose-dependently inhibited BV-induced sustained nociception and inflammation, but not the mechanical hyperalgesia. Topical pre-treatment of the sciatic nerve with 1% capsaicin significantly blocked the inhibitory effects of the PKC inhibitor on BV-induced inflammation, but not the persistent flinching response. These results indicate that peripheral PKA and PKC involvements in BV-induced pain behaviors differ, and capsaicin-sensitive afferents appear to participate in the pro-inflammatory role of PKC in the BV pain model. Findings from the present study also suggest that targeting specific peripheral protein kinases might prove effective in the treatment of persistent pain and inflammation.

• Authors: Hui-Sheng Chen, Jing Lei, Xiang He, Fang Qu, Yang Wang, Wei-Wei Wen, Hao-Jun You, Lars Arendt-Nielsen
• Journal: Pain (Pain) Vol. 135 Issue 1-2 Pg. 31-6 (Mar 2008) ISSN: 1872-6623 [Electronic] United States
• PMID: 17544210 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bee Venoms
• Enzyme Inhibitors
• Isoquinolines
• Sulfonamides
• Cyclic AMP-Dependent Protein Kinases
• Protein Kinase C
• N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide

Topics

• Analysis of Variance
• Animals
• Bee Venoms (administration & dosage)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Enzyme Inhibitors (administration & dosage)
• Functional Laterality
• Hyperalgesia (chemically induced, prevention & control)
• Inflammation (chemically induced, prevention & control)
• Injections, Subcutaneous (methods)
• Isoquinolines (administration & dosage)
• Male
• Pain (chemically induced, prevention & control)
• Pain Measurement
• Plethysmography (methods)
• Protein Kinase C (metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Sulfonamides (administration & dosage)