Inflammation and pain sensitivity: effects of leukotrienes D4, B4 and prostaglandin E1 in the rat paw.

Leukotrienes (LT's) and prostaglandins (PG's) have been proposed as mediators of vascular permeability changes in inflammatory reactions. Also, prostaglandins, especially of the E-type, have been shown to enhance pain responses. In the present studies in rats, the effects of LTB4 and LTD4 on edema and pain thresholds were examined in combination with PGE1 and/or brewer's yeast. Subplantar injections of LTD4 or LTB4 induced small increases in paw thickness which were potentiated by the co-administration of PGE1. LTD4 alone had no significant effect on the development of the yeast paw edema. LTB4 was found to reduce significantly the yeast edema and this reduction could be reversed by administration PGE1. A small but significant decrease in pain threshold was caused by PGE1 and this was significantly enhanced in the presence of LTD4. LTB4, like PGE1, was found to cause slight hyperalgesia but no synergy between the two agents was observed. LTD4 was found to have no effect on the initial hypoalgesia or subsequent development of hyperalgesia caused by brewer's yeast. Both LTB4 and PGE1, however, prevented the initial hypoalgesia and significantly reduced the latency for development of yeast induced hyperalgesia. These effects of LTB4 are discussed in terms of possible release of cyclooxygenase products.