the eicosanoids formed in the alox12 (i.e. arachidonate-12-lipoxygnease) pathway of arachidonic acid metabolism, 12"s"-hydroperoxy-5"z",8"z",10"e",14"z"-eicosatetraenoic acid (i.e. 12"s"-hpete; see 12-hydroxyeicosatetraenoic acid) and the hepoxilins (hx), hxa3 (i.e. 8"r/s"-hydroxy-11,12-oxido-5"z",9"e",14"z"-eicosatrienoic acid) and hxb3 (i.e. 10"r/s"-hydroxy-11,12-oxido-5"z",8"z",14"z"-eicosatrienoic acid) (see hepoxilin#pain perception) directly activate trpa1 and thereby contribute to the hyperalgesia and tactile allodynia responses of mice to skin inflammation. in this animal model of pain perception, the hepoxilins are released in spinal cord and directly activate trpa (and also trpv1) receptors to augment the perception of pain. 12"s"-hpete, which is the direct precursor to hxa3 and hxb3 in the alox12 pathway, may act only after being converted to these hepoxilins. the epoxide, 4,5-epoxy-8"z",11"z",14"z"-eicosatrienoic acid (4,5-eet) made by the metabolism of arachidonic acid by any one of several cytochrome p450 enzymes (see epoxyeicosatrienoic acid) likewise directly activates trpa1 to amplify pain perception.