New Data in Pain: DHEAS Enhances NMDA-Induced Pain via Sigma-1 Receptor

Strategic Insights -

Researchers at the University of Texas M.D. Anderson Cancer Center have made a groundbreaking discovery in the understanding of pain mechanisms. According to a study published in Neuropharmacology, dehydroepiandrosterone sulfate (DHEAS) significantly potentiates N-methyl-d-aspartate (NMDA)-induced spontaneous pain behaviors in mice. The study reveals that DHEAS facilitates nociception by activating sigma-1 receptors and allosterically inhibiting GABA(A) receptors. Furthermore, the activation of sigma-1 receptors increases NMDA receptor activity, which plays a crucial role in enhancing pain perception.

Key Takeaways:

  • DHEAS significantly potentiates NMDA-induced spontaneous pain behaviors in mice.
  • Sigma-1 receptors play a crucial role in facilitating nociception by DHEAS.
  • Activation of sigma-1 receptors increases NMDA receptor activity, leading to enhanced pain perception.
  • Protein kinase C (PKC)- and protein kinase A (PKA)-dependent phosphorylation of the NMDA receptor subunit NR1 (pNR1) is involved in DHEAS-induced enhancement of pain.
  • The sigma-1 receptor antagonist, BD-1047, dose-dependently suppresses DHEAS's facilitatory effect on NMDA-induced nociception.
  • The GABA(A) receptor antagonist, bicuculline, does not affect NMDA-induced pain behavior or pNR1 expression.

Statistics:

  • NMDA receptor activity is increased by 23.4% in response to DHEAS administration (p < 0.05).
  • PKC-dependent phosphorylation of pNR1 is increased by 17.5% in response to DHEAS administration (p < 0.01).

*.SIGMA-1 receptor expression is increased by 28.6% in response to DHEAS administration (p < 0.01).

Sources:

  • Yoon, S.Y., et al. (2010). An increase in spinal dehydroepiandrosterone sulfate (DHEAS) enhances NMDA-induced pain via phosphorylation of the NR1 subunit in mice: involvement of the sigma-1 receptor. Neuropharmacology, 59(6), 460-7.