Journal
NEUROSCIENCE
Volume 148, Issue 4, Pages 1015-1020Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2007.07.006
Keywords
sex differences; estrogen; pain
Categories
Funding
- NCCIH NIH HHS [R24 AT002681-04, R24 AT002681] Funding Source: Medline
- NIDDK NIH HHS [1 P50 DK64539, R01 DK058173, DK58173, P50 DK064539-06, R01 DK058173-07, P50 DK064539] Funding Source: Medline
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Women have greater temporal summation of experimental pain stimuli and also have a higher propensity for developing chronic visceral pain conditions. Sex hormone-mediated regulation of N-methyl-D-aspartic acid receptors (NMDARs) in nociceptive pathways is a plausible mechanism that may underlie these phenomena. The aim of this study was to compare the effect of 17-beta-estradiol (E2) in modulation of NMDAR activity in adult male and female rat dorsal root ganglia (DRG) neurons. DRG neurons were collected from adult male or female rats and grown in short-term culture in steroid-free media. NMDAR currents were recorded on small to medium size neurons by Whole cell patch clamp using rapid perfusion with saturating concentrations of N-methyl-D-aspartic acid and glycine in the absence of extracellular Mg2+. We found that the average density of NMDAR currents was 2.8-fold larger in DRG neurons from female rats compared with male rats (P<0.0001). Addition of 100 nM E2 increased NMDAR currents 55 +/- 15% in female neurons, but only 19 +/- 7% in male neurons. Potentiation was maximal after 20-40 min and dose dependent with an apparent 50% excitatory concentration of 17-23 nM. This effect was mimicked by E2 conjugated to BSA and attenuated by pretreatment with the protein tyrosine kinase inhibitor lavendustin A (1 mu M) or the estrogen receptor (ER) antagonist, ICI 182,780 (1 mu M), strongly suggesting activation of a cell surface ER acting through a non-genomic mechanism involving protein tyrosine kinases to increase NMDAR currents. These results identify sex-based differences in both the basal expression and the regulation of the NMDARs in DRG neurons. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.
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