NaHS modulates astrocytic EAAT2 expression to impact SNI-induced neuropathic pain and depressive-like behaviors

Sci Rep. 2025 Jan 22;15(1):2874. doi: 10.1038/s41598-025-86885-0.

Abstract

The potential role of hydrogen sulfide (H2S) in the modulation of neuropathic pain is increasingly recognized. This study investigated the therapeutic effect of intraperitoneal injection of the H2S donor sodium hydrosulfide (NaHS) on neuropathic pain. Utilizing the spared nerve injury (SNI) model in mice, the research investigates the role of astrocytes and the excitatory neurotransmitter glutamate in chronic pain. The findings reveal that sodium hydrosulfide (NaHS), an H2S donor, effectively enhances the mechanical pain threshold and thermal pain escape latency in SNI mice. The study further demonstrates NaHS's potential in reducing glutamate levels in the spinal cord and the discharge frequency of neurons in the primary somatosensory cortex hindlimb region (S1HL) brain area, suggesting a novel therapeutic approach for neuropathic pain through the modulation of astrocyte function and EAAT2 expression.

Keywords: Astrocytes; EAAT2; Neuropathic pain; Sodium hydrosulfide.

MeSH terms

  • Animals
  • Astrocytes* / drug effects
  • Astrocytes* / metabolism
  • Behavior, Animal / drug effects
  • Depression / drug therapy
  • Depression / etiology
  • Depression / metabolism
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 2* / metabolism
  • Glutamic Acid / metabolism
  • Male
  • Mice
  • Neuralgia* / drug therapy
  • Neuralgia* / metabolism
  • Pain Threshold / drug effects
  • Somatosensory Cortex / drug effects
  • Somatosensory Cortex / metabolism
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Sulfides* / pharmacology

Substances

  • Excitatory Amino Acid Transporter 2
  • Slc1a2 protein, mouse
  • Sulfides
  • sodium bisulfide
  • Glutamic Acid