Melittin, the Major Pain-Producing Substance of Bee Venom

Direct actions of melittin on primary nociceptor cells. Following subcutaneous injection of a low concentration of melittin, phospholipase A2 (PLA2) is activated and catalyzes the production of arachidonic acid (AA) from phospholipids. AA is further catalyzed by lipoxygenases (LOXs) to produce hydroperoxyeicosatetraenoic acids (HETEs) that serve as endogenous ligands to open TRPV1 receptor channels, leading to Ca2+ influx and membrane depolarization. Meanwhile, AA is also catalyzed by cyclooxygenases (COXs) to produce PGs that enhance the activity of TRPV1, leading to sensitization of the primary nociceptors