Differential Roles of Peripheral Mitogen-Activated Protein Kinase Signal Transduction Pathways in Bee Venom-Induced Nociception and Inflammation in Conscious Rats

Intraplantar injection of bee venom (BV) produces persistent spontaneous nociception (PSN) and hyperalgesia, as well as obvious inflammatory swelling, in the paws of injected rats. The present study was designed to determine the peripheral roles of mitogen-activated protein kinase (MAPK) signal transduction pathways in BV-induced nociception and inflammation. We examined the effect of intraplantar injection of an ERK1/2 inhibitor, PD98059, and a p38 inhibitor, SB2021190, on BV-induced PSN, mechanical hyperalgesia, and inflammatory swelling. We found that (1) pretreatment with SB202190 (0.1 to 10 mu g) had no effect on BV-induced PSN, whereas pretreatment with PD98059 (0.1 to 100 mu g) produced a significant and dose-dependent inhibition of BV-induced PSN; (2) pretreatment with PD98059 (0.1 to 100 mu g) had no effect on BV-induced decreases in paw withdrawal mechanical threshold (PWMT), while pretreatment with SB202190 (0.1 to 10 mu g) produced an obvious prevention of the BV-induced decrease in PWMT; and (3) pretreatment with PD98059 (0.1 to 100 mu g) had no effect on BV-induced increase in paw volume (PV), whereas pretreatment with SB202190 (0.1 to 10 mu g) produced a dose-related inhibition of BV-induced increases in PV. No contralateral drug treatments, even at the highest dose, had any effect on BV-induced PSN, PWMT or PV, ruling out the systemic effect of these drugs. These results suggest that peripheral MAPK signal transduction pathways may play differential roles in bee venom-induced nociception and inflammation. Targeting specific peripheral MAPKs might prove effective in the treatment of persistent pain and inflammation. Perspective: The present article showed that intraplantar injection of different MAPK inhibitors produced differential effects on bee venom-induced nociception and inflammation, suggesting that the peripheral MAPK signal transduction pathways have differential roles. Targeting specific peripheral MAPKs might prove effective in the treatment of persistent pain and inflammation. (c) 2009 by the American Pain Society