Laboratory Investigation
Neurosteroid dehydroepiandrosterone sulphate enhances pain transmission in rat spinal cord dorsal horn

https://doi.org/10.1016/j.bja.2019.03.026Get rights and content
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Abstract

Background

The neurosteroid dehydroepiandrosterone sulphate (DHEAS) activates the sigma-1 receptor, inhibits gamma-aminobutyric acid A (GABAA) 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 Ca2+-dependent but not sigma-1 and N-methyl-d-aspartate receptor-dependent. DHEAS suppressed the frequency of miniature inhibitory postsynaptic currents in a GABAA 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 GABAA receptor.

Keywords

analgesia
gamma-aminobutyric acid
glutamate
neuropathic pain
neurosteroids
nociception
spinal cord dorsal horn
synaptic transmission

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