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.