Glucosylceramide synthase inhibitor ameliorates chronic inflammatory pain

J Pharmacol Sci. 2024 Dec;156(4):235-238. doi: 10.1016/j.jphs.2024.10.003. Epub 2024 Oct 15.

Abstract

Gangliosides play pivotal roles in neuronal tissue processes, such as axonal elongation, synaptic transmission, and neuronal degeneration. Several studies have shown that mice injected with gangliosides synthesized from glucosylceramide exhibit mechanical allodynia. Thus, we hypothesized that glucosylceramide synthase inhibitors affect nociceptive behavior. We investigated the analgesic effect of intrathecal glucosylceramide inhibition on bilateral allodynia caused by prolonged unilateral hind paw inflammation in mice. Repeated administration of a glucosylceramide inhibitor reduced mechanical allodynia in both inflamed and non-inflamed hind paws. These results suggested that ganglioside reduction is critical for analgesia during inflammatory pain.

Keywords: Ganglioside; Glucosylceramide synthase; Inflammatory pain.

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Chronic Pain / drug therapy
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Gangliosides
  • Glucosylceramides
  • Glucosyltransferases* / antagonists & inhibitors
  • Hyperalgesia* / drug therapy
  • Hyperalgesia* / etiology
  • Inflammation* / drug therapy
  • Injections, Spinal
  • Male
  • Mice

Substances

  • Glucosyltransferases
  • ceramide glucosyltransferase
  • Glucosylceramides
  • Enzyme Inhibitors
  • Gangliosides
  • Analgesics