mRNA Expression of Mineralocorticoid and Glucocorticoid Receptors in Human and Mouse Sensory Neurons of the Dorsal Root Ganglia.

BACKGROUND

Corticosteroid receptors, including mineralocorticoid receptor (MR) and glucocorticoid receptor (GR), play important roles in inflammatory pain in the dorsal root ganglion (DRG). Although it is widely known that activating the GR reduces inflammatory pain, it has recently been shown that MR activation contributes to pain and neuronal excitability in rodent studies. Moreover, little is known about the translation of this work to humans, or the mechanisms through which corticosteroid receptors regulate inflammatory pain.

METHODS

Corticosteroid receptor expression in human and mouse DRGs was characterized. RNAscope was used to perform high-resolution in situ hybridization for GR and MR mRNAs and to examine their colocalization with markers for nociceptors ( SCN10A , Na V 1.8 mRNA) and Aβ mechanoreceptors ( KCNS1 , Kv9.1 mRNA) in human DRG and C57BL/6J mouse DRG samples.

RESULTS

GR and MR mRNAs are expressed in almost all DRG neurons across species. The 2 receptors colocalize in 99.2% of human DRG neurons and 95.9% of mouse DRG neurons ( P = .0004, Fisher exact test). In both human and mouse DRGs, the large-diameter KCNS1+ Aβ mechanoreceptors showed a significantly higher MR/GR ratio (MR-leaning) compared to KCNS1- neurons (human: 0.23 vs 0.04, P = .0002; mouse: 0.35 vs -0.24, P < .0001; log ratios, unpaired t test), whereas small-diameter SCN10A+ nociceptive neurons showed a significantly lower MR/GR ratio (GR-leaning) compared to SCN10A- neurons (human: -0.02 vs 0.18, P = .0001; mouse: -0.16 vs 0.08, P < .0001; log ratios, unpaired t test).

CONCLUSIONS

These findings indicate that mouse corticosteroid receptor mRNA expression reflects human expression in the DRG, and that mice could be a suitable model for studying corticosteroid receptor involvement in pain. Additionally, this study supports the translatability of rodent data to humans for the use of more selective corticosteroids at the DRG in pain treatments.