Temporal and spatial summation of laser heat stimuli in cultured nociceptive neurons of the rat.

We studied the efficacy of a near-infrared laser (1475 nm) to activate rat dorsal root ganglion (DRG) neurons with short punctate radiant heat pulses (55 µm diameter) and investigated temporal and spatial summation properties for the transduction process for noxious heat at a subcellular level. Strength-duration curves (10-80 ms range) indicated a minimum power of 30.2mW for the induction of laser-induced calcium transients and a chronaxia of 13.

The capsaicin receptor TRPV1 is the first line defense protecting from acute non damaging heat: a translational approach.

Background: Pain is the vital sense preventing tissue damage by harmful noxious stimuli. The capsaicin receptor TRPV1 is activated by noxious temperatures, however, acute heat pain is only marginally affected in mice after TRPV1 knockout but completely eliminated in mice lacking TRPV1 positive fibers. Exploring contribution of candidate signal transduction mechanisms to heat pain in humans needs translational models.

Analyses of Synthetic N-Acyl Dopamine Derivatives Revealing Different Structural Requirements for Their Anti-inflammatory and Transient-Receptor-Potential-Channel-of-the-Vanilloid-Receptor-Subfamily-Subtype-1 (TRPV1)-Activating Properties.

We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for the activation of transient-receptor-potential channels of the vanilloid-receptor subtype 1 (TRPV1) and inhibition of inflammation. The potency of NOD in activating TRPV1 was significantly higher compared with those of variants in which the ortho-dihydroxy groups were acetylated, one of the hydroxy groups was omitted ( N-octanoyl tyramine), or the ester functionality consisted of a bulky fatty acid ( N-pivaloyl dopamine). Shortening of the amide linker (ΔNOD) slightly increased its potency, which was further increased when the carbonyl and amide groups (ΔNODR) were interchanged.

Radiofluorinated N-Octanoyl Dopamine ([F]F-NOD) as a Tool To Study Tissue Distribution and Elimination of NOD in Vitro and in Vivo.

To mitigate pretransplantation injury in organs of potential donors, N-octanoyl dopamine (NOD) treatment might be considered as it does not affect hemodynamic parameters in braindead (BD) donors. To better assess optimal NOD concentrations for donor treatment, we report on the fast and facile radiofluorination of the NOD-derivative [F]F-NOD [F]5 for in vivo assessment of NOD's elimination kinetics by means of PET imaging. [F]5 was synthesized in reproducibly high radiochemical yields and purity (>98%) as well as high specific activities (>20 GBq/μmol).

N-octanoyl dopamine treatment exerts renoprotective properties in acute kidney injury but not in renal allograft recipients.

Background: N-octanoyl dopamine (NOD) treatment improves renal function when applied to brain dead donors and in the setting of warm ischaemia-induced acute kidney injury (AKI). Because it also activates transient receptor potential vanilloid type 1 (TRPV1) channels, we first assessed if NOD conveys its renoprotective properties in warm ischaemia-induced AKI via TRPV1 and secondly, if renal transplant recipients also benefit from NOD treatment.

Methods: We induced warm renal ischaemia in Lewis, wild-type (WT) and TRPV1(-/-) Sprague-Dawley (sd) rats by clamping the left renal artery for 45 min.