Ablation of spinal cord estrogen receptor α-expressing interneurons reduces chemically induced modalities of pain and itch

Tran, M., Braz, J. M., Hamel, K., Kuhn, J., Todd, A. J. and Basbaum, A. I. (2020) Ablation of spinal cord estrogen receptor α-expressing interneurons reduces chemically induced modalities of pain and itch. Journal of Comparative Neurology, 528(10), pp. 1629-1643. (doi: 10.1002/cne.24847) (PMID:31872868) (PMCID:PMC7317200)

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Abstract

Estrogens are presumed to underlie, at least in part, the greater pain sensitivity and chronic pain prevalence that women experience compared to men. Although previous studies revealed populations of estrogen receptor‐expressing neurons in primary afferents and in superficial dorsal horn neurons, there is little to no information as to the contribution of these neurons to the generation of acute and chronic pain. Here we molecularly characterized neurons in the mouse superficial spinal cord dorsal horn that express estrogen receptor α (ERα) and explored the behavioral consequences of their ablation. We found that spinal ERα‐positive neurons are largely excitatory interneurons and many coexpress substance P, a marker for a discrete subset of nociceptive, excitatory interneurons. After viral, caspase‐mediated ablation of spinal ERα‐expressing cells, we observed a significant decrease in the first phase of the formalin test, but in male mice only. ERα‐expressing neuron‐ablation also reduced pruritogen‐induced scratching in both male and female mice. There were no ablation‐related changes in mechanical or heat withdrawal thresholds or in capsaicin‐induced nocifensive behavior. In chronic pain models, we found no change in Complete Freund's adjuvant‐induced thermal or mechanical hypersensitivity, or in partial sciatic nerve injury‐induced mechanical allodynia. We conclude that ERα labels a subpopulation of excitatory interneurons that are specifically involved in chemically evoked persistent pain and pruritogen‐induced itch.

Item Type:Articles
Additional Information:The studies were supported by NIH R35097306 and a grant from the Wellcome Trust.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Todd, Professor Andrew
Authors: Tran, M., Braz, J. M., Hamel, K., Kuhn, J., Todd, A. J., and Basbaum, A. I.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Journal of Comparative Neurology
Publisher:Wiley
ISSN:0021-9967
ISSN (Online):1096-9861
Published Online:24 December 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Journal of Comparative Neurology 528(10):1629-1643
Publisher Policy:Reproduced under a Creative Commons License

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