Pentobarbital may protect against neurogenic inflammation after surgery via inhibition of substance P release from peripheral nerves of rats

Neurosci Lett. 2022 Feb 6:771:136467. doi: 10.1016/j.neulet.2022.136467. Epub 2022 Jan 19.

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 Ca2+ 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.

Keywords: Anti-Inflammatory Effect; Barbiturate; Capsaicin; Ketamine; Neurogenic Inflammation; Substance P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Calcium Channels / metabolism
  • Capsaicin / pharmacology
  • Cells, Cultured
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Ketamine / pharmacology
  • Male
  • Neurogenic Inflammation / drug therapy*
  • Neurogenic Inflammation / metabolism
  • Pentobarbital / pharmacology
  • Pentobarbital / therapeutic use*
  • Peripheral Nerves / drug effects
  • Peripheral Nerves / metabolism*
  • Rats
  • Rats, Wistar
  • Sensory System Agents / pharmacology
  • Substance P / metabolism*
  • TRPV Cation Channels / metabolism

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Calcium Channels
  • Sensory System Agents
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Substance P
  • Ketamine
  • Pentobarbital
  • Capsaicin