Xenon fails to inhibit capsaicin-evoked CGRP release by nociceptors in culture

► Xenon fails to inhibit nociceptor signalling ► Capsaicin-evoked CGRP release is not reduced by xenon ► Xenon fails to produce an analgesic effect on peripheral nociceptors. To investigate whether the xenon-induced inhibition of the transient receptor potential vanilloid type 1 (TRPV1) ion channel in rat dorsal root ganglion (DRG) neurons reduces nociceptive processing, we examined the effect of xenon in reducing the release of calcitonin gene-related peptide (CGRP) from those neurons. We found that exposure to xenon failed to effect a reduction of capsaicin-evoked CGRP release from cultured primary sensory neurons when stimulated by capsaicin. This finding suggests that xenon acts on several molecular targets on nociceptive primary sensory neurons, and that xenon's action on one, or more, of those targets serves to offset the inhibitory, pro-analgesic, effect of xenon on TRPV1. It is concluded that xenon may not produce any analgesic effect through peripheral nociceptors.