Ablation of spinal cord estrogen receptor α‐expressing interneurons reduces chemically induced modalities of pain and itch. Issue 10 (6th January 2020)

• Record Type: Journal Article
• Authors: Tran, May; Braz, Joao Manuel; Hamel, Katherine; Kuhn, Julia; Todd, Andrew J.; Basbaum, Allan I.
• Is Part Of: Journal of comparative neurology. Volume 528:Issue 10(2020)
• Page Start: 1629
• Page End: 1643
• Publication Date: 2020-01-06
• Subjects: estrogen receptor -- excitatory interneurons -- itch -- pain -- spinal cord; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.24847
• Languages: English
• ISSNs: 0021-9967

Abstract

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. Abstract : Estrogens underlie, at least in part, the greater pain sensitivity and chronic pain prevalence that women experience compared to men. Previous studies revealed populations of estrogen receptor‐expressing neurons in primary afferents and in superficial dorsal horn neurons, but there is limited 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. The great majority of spinal ERα‐positive neurons are excitatory interneurons and many co‐express the neuropeptide, substance P. After viral, caspase‐mediated ablation of spinal ERα‐expressing cells, we did not observe changes in acute mechanical or heat pain processing, but recorded significant changes in the response to chemically‐evoked persistent pain behavior as well as pruritogen‐evoked itch.