Leukotriene B4 produces hyperalgesia in humans

During inflammation, pain receptors are sensitized by inflammatory mediators causing hyperalgesia. Leukotriene B4 (LTB4) is a potent chemoattractant for polymorphonuclear leukocytes in humans in vivo. In the present study we have demonstrated a reduction of the pain threshold in humans after intracutaneous deposition of LTB4. The pain threshold was quantitated by the "Marstock" method in which the testsubject reversed the direction of the temperature change of a thermostimulator whenever a painful temperature was reached. This enabled a quantitative description of the persons pain sensibility. After intracutaneous infiltration of LTB4 (10 microM) a highly significant decrease in the pain threshold could be detected as compared to control with a maximum effect between 6 and 24 h. The decrease in the pain threshold amounted to less than 15% when compared to control and corresponds with the published kinetics of the influx of polymorphonuclear leukocytes. These results support the hypothesis that LTB4 produces hyperalgesia indirectly through recruitment of polymorphonuclear leukocytes and not via a direct effect on the pain receptors. Inhibition of the lipoxygenase might be an advantageous adjunct to the effect of the Non Steroidal Anti-Inflammatory Drugs.