Neurosteroid Dehydroepiandrosterone Sulphate Enhances Pain Transmission in Rat Spinal Cord Dorsal Horn

Overview

Journal Br J Anaesth

Publisher Elsevier

Specialty Anesthesiology

Date 2019 Apr 30

PMID 31030988

Citations 4

Authors

Goh Yamamoto

Yoshinori Kamiya

Mika Sasaki

Miho Ikoma

Hiroshi Baba

Tatsuro Kohno

Affiliations

Soon will be listed here.

Abstract

Background: The neurosteroid dehydroepiandrosterone sulphate (DHEAS) activates the sigma-1 receptor, inhibits gamma-aminobutyric acid A (GABA) and glycine receptors, and induces hyperalgesic effects. Although its effects have been studied in various tissues of the nervous system, its synaptic mechanisms in nociceptive pathways remain to be elucidated.

Methods: The threshold of mechanical hypersensitivity and spontaneous pain behaviour was assessed using the von Frey test in adult male Wistar rats after intrathecal administration of DHEAS. We also investigated the effects of DHEAS on synaptic transmission in the spinal dorsal horn using slice patch-clamp electrophysiology.

Results: Intrathecally administered DHEAS elicited dose-dependent mechanical hyperalgesia and spontaneous pain behaviours (withdrawal threshold: saline; 51.0 [20.1] g, 3 μg DHEAS; 14.0 [7.8] g, P<0.01, 10 μg DHEAS; 6.9 [5.2] g, 15 min after administration, P<0.001). DHEAS at 100 μM increased the frequency of miniature postsynaptic currents in the rat dorsal spinal horn; this increase was extracellular Ca-dependent but not sigma-1 and N-methyl-d-aspartate receptor-dependent. DHEAS suppressed the frequency of miniature inhibitory postsynaptic currents in a GABA receptor- and sigma-1 receptor-dependent manner.

Conclusions: These results suggest that DHEAS participates in the pathophysiology of nociceptive synaptic transmission in the spinal cord by potentiation of glutamate release and inhibition of the GABA receptor.

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References

Mensah-Nyagan A, Beaujean D, Luu-The V, Pelletier G, Vaudry H . Neurosteroids: expression of steroidogenic enzymes and regulation of steroid biosynthesis in the central nervous system. Pharmacol Rev. 1999; 51(1):63-81. View

Shen W, Mennerick S, Zorumski E, Covey D, Zorumski C . Pregnenolone sulfate and dehydroepiandrosterone sulfate inhibit GABA-gated chloride currents in Xenopus oocytes expressing picrotoxin-insensitive GABA(A) receptors. Neuropharmacology. 1999; 38(2):267-71. DOI: 10.1016/s0028-3908(98)00172-5. View

Alonso G, Phan V, Guillemain I, Saunier M, Legrand A, Anoal M . Immunocytochemical localization of the sigma(1) receptor in the adult rat central nervous system. Neuroscience. 2000; 97(1):155-70. DOI: 10.1016/s0306-4522(00)00014-2. View

Scott D, Blanpied T, Swanson G, Zhang C, Ehlers M . An NMDA receptor ER retention signal regulated by phosphorylation and alternative splicing. J Neurosci. 2001; 21(9):3063-72. PMC: 6762585. View

Ueda H, Inoue M, Yoshida A, Mizuno K, Yamamoto H, Maruo J . Metabotropic neurosteroid/sigma-receptor involved in stimulation of nociceptor endings of mice. J Pharmacol Exp Ther. 2001; 298(2):703-10. View

Maksay G, Laube B, Betz H . Subunit-specific modulation of glycine receptors by neurosteroids. Neuropharmacology. 2001; 41(3):369-76. DOI: 10.1016/s0028-3908(01)00071-5. View

Abdrachmanova G, Chodounska H, Vyklicky Jr L . Effects of steroids on NMDA receptors and excitatory synaptic transmission in neonatal motoneurons in rat spinal cord slices. Eur J Neurosci. 2001; 14(3):495-502. DOI: 10.1046/j.0953-816x.2001.01663.x. View

Zhang H, Cuevas J . Sigma receptors inhibit high-voltage-activated calcium channels in rat sympathetic and parasympathetic neurons. J Neurophysiol. 2002; 87(6):2867-79. DOI: 10.1152/jn.2002.87.6.2867. View

Meyer D, Carta M, Donald Partridge L, Covey D, Valenzuela C . Neurosteroids enhance spontaneous glutamate release in hippocampal neurons. Possible role of metabotropic sigma1-like receptors. J Biol Chem. 2002; 277(32):28725-32. DOI: 10.1074/jbc.M202592200. View

10.

Hsu F, Waldeck R, Faber D, Smith S . Neurosteroid effects on GABAergic synaptic plasticity in hippocampus. J Neurophysiol. 2003; 89(4):1929-40. PMC: 2909183. DOI: 10.1152/jn.00780.2002. View

11.

De Roo M, Rodeau J, Schlichter R . Dehydroepiandrosterone potentiates native ionotropic ATP receptors containing the P2X2 subunit in rat sensory neurones. J Physiol. 2003; 552(Pt 1):59-71. PMC: 2343311. DOI: 10.1113/jphysiol.2003.046078. View

12.

Mtchedlishvili Z, Kapur J . A presynaptic action of the neurosteroid pregnenolone sulfate on GABAergic synaptic transmission. Mol Pharmacol. 2003; 64(4):857-64. DOI: 10.1124/mol.64.4.857. View

13.

Lhullier F, Riera N, Nicolaidis R, Junqueira D, Dahm K, Cipriani F . Effect of DHEA glutamate release from synaptosomes of rats at different ages. Neurochem Res. 2004; 29(2):335-9. DOI: 10.1023/b:nere.0000013735.50736.0a. View

14.

Lhullier F, Nicolaidis R, Riera N, Cipriani F, Junqueira D, Dahm K . Dehydroepiandrosterone increases synaptosomal glutamate release and improves the performance in inhibitory avoidance task. Pharmacol Biochem Behav. 2004; 77(3):601-6. DOI: 10.1016/j.pbb.2003.12.015. View

15.

Sliwinski A, Monnet F, Schumacher M, Morin-Surun M . Pregnenolone sulfate enhances long-term potentiation in CA1 in rat hippocampus slices through the modulation of N-methyl-D-aspartate receptors. J Neurosci Res. 2004; 78(5):691-701. DOI: 10.1002/jnr.20332. View

16.

Kibaly C, Patte-Mensah C, Mensah-Nyagan A . Molecular and neurochemical evidence for the biosynthesis of dehydroepiandrosterone in the adult rat spinal cord. J Neurochem. 2005; 93(5):1220-30. DOI: 10.1111/j.1471-4159.2005.03113.x. View

17.

Smith C, McMahon L . Estrogen-induced increase in the magnitude of long-term potentiation occurs only when the ratio of NMDA transmission to AMPA transmission is increased. J Neurosci. 2005; 25(34):7780-91. PMC: 6725261. DOI: 10.1523/JNEUROSCI.0762-05.2005. View

18.

Monnet F, Maurice T . The sigma1 protein as a target for the non-genomic effects of neuro(active)steroids: molecular, physiological, and behavioral aspects. J Pharmacol Sci. 2006; 100(2):93-118. DOI: 10.1254/jphs.cr0050032. View

19.

Fodor L, Boros A, Dezso P, Maksay G . Expression of heteromeric glycine receptor-channels in rat spinal cultures and inhibition by neuroactive steroids. Neurochem Int. 2006; 49(6):577-83. DOI: 10.1016/j.neuint.2006.04.013. View

20.

Chen L, Miyamoto Y, Furuya K, Dai X, Mori N, Sokabe M . Chronic DHEAS administration facilitates hippocampal long-term potentiation via an amplification of Src-dependent NMDA receptor signaling. Neuropharmacology. 2006; 51(3):659-70. DOI: 10.1016/j.neuropharm.2006.05.011. View