Objective: To optimize the dose of histamine and 4-aminopyridine (4-AP) by central composite design response plane method, in order to establish a new model of pruritus in guinea pigs.
Methods: The experiment was arranged with a star point design. 0.5 mL of different itching agents were injected subcutaneously at the depilation site in each group, and the scratch latency and scratch times of guinea pigs within 30 minutes were recorded. The best itching formula was selected by comprehensive scoring method. The guinea pig model was evaluated by observing the behavioral changes and measuring the contents of histamine and interleukin-6 (IL-6) in blood.
Results: The behavioral experiment showed that the scratching times in the combined group were significantly increased (P<0.01) and the scratching latency was significantly shortened (P<0.01) compared with histamine group and 4-AP group within 30 minutes. The number of scratches in 4-AP group was significantly higher than that in histamine group within 30 minutes (P<0.01). Compared with the control group, the concentration of histamine in the serum of guinea pigs in the combination group and histamine group increased significantly (P<0.05 or P<0.01), but the increase in the combination group was lower than that in the histamine group (P<0.05); Compared with the control group, the serum IL-6 concentration in histamine group, 4-AP group and combination group were significantly higher (P<0.01 or P<0.05), and the combination group was significantly higher than histamine group and 4-AP group. Pathological examination showed that there were different degrees of inflammatory cell proliferation in each model group, and the reaction in the combined group was more obvious.
Conclusion: The optimized formula (combination group) model in this experiment is easy to realize and has good repeatability.