Pentobarbital may protect against neurogenic inflammation after surgery via inhibition of substance P release from peripheral nerves of rats. (6th February 2022) - Onizuka, Chiori
Highlights: Neurogenic inflammation originates from local release of inflammatory mediators, such as substance P (SP), by primary afferent neurons after noxious stimuli like surgery. Cultured dorsal root ganglion (DRG) neurons have both central and peripheral branches. Pentobarbital significantly inhibited capsaicin-induced, but not high K + -induced, SP release from rat DRG cells. However, a high concentration of ketamine did not block SP release. Thus, the inhibitory effects of pentobarbital on SP release from peripheral terminals may protect against neurogenic inflammation after surgery. Abstract: The inflammatory response related to surgery is considered surgical inflammation. Most anesthetic agents directly or indirectly suppress the immune response. However, the intravenous anesthetics pentobarbital and ketamine were reported to inhibit the lipopolysaccharide-induced inflammatory response such as cytokines formation. Neurogenic inflammation is inflammation originating from the local release of inflammatory mediators, such as substance P (SP), by primary afferent neurons after noxious stimuli like surgery. Thus, in this study, we examined whether pentobarbital and ketamine suppress SP release from cultured dorsal root ganglion (DRG) neurons. DRG cells were dissected from male Wistar rats. Released SP was measured by radioimmunoassay. We demonstrated that higher concentrations of pentobarbital (100–1, 000 μM) significantly inhibited capsaicin (100 nM)-induced, but not high K + (50 mM)-induced, SP release from DRG cells, although a high concentration of ketamine (1 mM) did not. This study revealed that pentobarbital functions between the activation of vanilloid receptor subtype 1 (TRPV1) receptors, to which capsaicin selectively binds, and the opening of voltage-operated Ca 2+ channels (VOCC) in the nerve endings. Therefore, the anti-inflammatory action of pentobarbital is mediated through different mechanisms than those of ketamine. Thus, the inhibitory effect of pentobarbital on SP release from peripheral terminals may protect against neurogenic inflammation after surgery.