抄録
Prostaglandin E2 (PGE2) is one of the inflammatory mediators that play important roles in nociceoption and hyperalgesia in inflamed tissues by exciting or sensitizing nociceptors. The capsaicin receptor TRPV1 is a non-selective cation channel expressed predominantly in unmyelinated C-fibers and activated not only by capsaicin, but also by protons or heat both of which cause pain in vivo. The functional interaction between TRPV1 and PGE2 was examined using electrophysiological and behavioral analyses. PGE2-induced thermal hyperalgesia was almost completely abolished in TRPV1-deficient mice. In HEK293 cells expressing cloned TRPV1 and EP1 receptors, PGE2 increased capsaicin-evoked TRPV1 currents through EP1 receptors in a PKC-dependent pathway. In addition, in the presence of PGE2, temperature threshold for TRPV1 activation was reduced from 40.8 to 30.9oC. Similar EP1-mediated increase in TRPV1 activity could be observed in mouse dorsal root ganglion neurons. In behavioral analyses, both PGE2-induced thermal hyperalgesia and inflammatory nociceptive responses were diminished in EP1-dificient mice. Thus, the potentiation of TRPV1 activity through EP1 activation might be one important mechanism underlying the nociceptive actions of PGE2. [Jpn J Physiol 54 Suppl:S44 (2004)]
