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Objective The bee venom test has long been used to evaluate the antinociceptive, antihyperalgesic and anti-inflammatory effects of endogenous and exogenous substances, however, the dose-effect of subcutaneous (s.c.) injection of bee venom on each pain-related behavior has not been validated.Thus, in the current report we used six doses (0.001, 0.005, 0.01, 0.05, 0.1, and 0.2 mg in 50 μL) of bee venom solution to see whether there are differences in responses.Methods Quantitative methods were used for evaluation of each pain-related behavior.Counting the number of paw flinches of each 5-min time block from 0-60 min was used to evaluate the intensity of persistent spontaneous nociception, while paw withdrawal thermal latency (PWTL, s) and paw withdrawal mechanical threshold (PWMT, g) were used to evaluate thermal and mechanical hyperalgesia, respectively.Measurements of paw volume, cross-dimensional paw thickness, skin temperature and volume of plasma extravasation were used to evaluate local inflammatory responses.Results Generally, there were significant differences in peak responses between persistent spontaneous nociception, PWTL, PWMT, and local inflammation following s.c.injection of bee venom.Specifically, there was a dose-dependent effect of bee venom on the number and time period of paw flinches, and the dose-effect curve showed a typical S that reached plateau at 0.1 mg.However, the peak% maximal possible effect (MPE) of bee venom on the reduction in PWTL and PWMT at 2 h after injection was caused by different doses of bee venom, namely 0.05 mg for PWTL and 0.01 mg for PWMT.These results suggest that the dose required for %MPE is different from each other in terms of persistent spontaneous nociception, thermal hyperalgesia and mechanical hyperalgesia.Furthermore, the dose for %MPE of four quantitative measurements was also different between paw volume (or thickness), plasma extravasation and skin temperature.The dose of 0.1 mg was required for %MPE of both paw volume and paw thickness, while that for plasma extravasation was 0.01 mg.There was no dose-related effect of bee venom on the changes in skin temperatures.Conclusion The dose-effect curves for bee venom-induced persistent spontaneous nociception, thermal hyperalgesia, mechanical hyperalgesia, and local inflammation are different in patterns, suggesting a need of different optimal doses of bee venom in evaluation of a given drug on different phenotypes of inflammatory pain processes.