The oxidized linoleic acid metabolite 12,13-DiHOME mediates thermal hyperalgesia during inflammatory pain.

Eicosanoids play a crucial role in inflammatory pain. However, there is very little knowledge about the contribution of oxidized linoleic acid metabolites in inflammatory pain and peripheral sensitization. Here, we identify 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME), a cytochrome P450-derived linoleic acid metabolite, as crucial mediator of thermal hyperalgesia during inflammatory pain.

The ubiquitin ligase MYCBP2 regulates transient receptor potential vanilloid receptor 1 (TRPV1) internalization through inhibition of p38 MAPK signaling.

The E3 ubiquitin ligase MYCBP2 negatively regulates neuronal growth, synaptogenesis, and synaptic strength. More recently it was shown that MYCBP2 is also involved in receptor and ion channel internalization. We found that mice with a MYCBP2-deficiency in peripheral sensory neurons show prolonged thermal hyperalgesia.

PAM mediates sustained inhibition of cAMP signaling by sphingosine-1-phosphate.

PAM (Protein Associated with Myc) is an almost ubiquitously expressed protein that is one of the most potent inhibitors of adenylyl cyclase activity known so far. Here we show that PAM is localized at the endoplasmic reticulum in HeLa cells and that upon serum treatment PAM is recruited to the plasma membrane, causing an inhibition of adenylyl cyclase activity. We purified the serum factor that induced PAM translocation and identified it as sphingosine-1-phosphate (S1P).