Effects of gabapentinoids on responses of primary cultures from rat dorsal root ganglia to inflammatory or somatosensory stimuli

J Basic Clin Physiol Pharmacol. 2020 Feb 20;31(4):/j/jbcpp.2020.31.issue-4/jbcpp-2019-0261/jbcpp-2019-0261.xml. doi: 10.1515/jbcpp-2019-0261.

Abstract

Background Gabapentinoids are known to reduce neuropathic pain. The aim of this experimental study was to investigate whether gabapentinoids exert anti-inflammatory and/or anti-nociceptive effects at the cellular level using primary cultures of rat dorsal root ganglia (DRG). Methods Cells from rat DRG were cultured in the presence of gabapentin or pregabalin, and we tested the effects of subsequent stimulation with lipopolysaccharide (LPS) on the expression of genes (real-time polymerase chain reaction) and production of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) by specific bioassays. Using Ca2+ imaging, we further investigated in neurons the effects of gabapentinoids upon stimulation with the TRPV-1 agonist capsaicin. Results There is a small influence of gabapentinoids on the inflammatory response to LPS stimulation, namely, a significantly reduced expression of IL-6. Pregabalin and gabapentin further seem to exert a moderate inhibitory influence on capsaicin-induced Ca2+ signals in DRG neurons. Conclusions Although the single inhibitory effects of gabapentinoids on inflammatory and nociceptive responses are moderate, a combination of both effects might provide an explanation for the proposed function of these substances as an adjuvant for the reduction of neuropathic pain.

Keywords: calcium imaging; cytokines; dorsal root ganglia; gabapentinoids; lipopolysaccharide.

MeSH terms

  • Analgesics / pharmacology
  • Animals
  • Capsaicin / pharmacology
  • Female
  • Gabapentin / pharmacology*
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / immunology
  • Ganglia, Spinal / metabolism
  • Inflammation / chemically induced
  • Inflammation / physiopathology*
  • Lipopolysaccharides / toxicity*
  • Male
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Neurons / drug effects
  • Pregabalin / pharmacology
  • Primary Cell Culture
  • Rats
  • Rats, Wistar
  • Sensory System Agents / pharmacology
  • Somatosensory Cortex / drug effects
  • Somatosensory Cortex / physiopathology*

Substances

  • Analgesics
  • Lipopolysaccharides
  • Sensory System Agents
  • Pregabalin
  • Gabapentin
  • Capsaicin