Sex differences in the inflammatory response of the mouse DRG and its connection to pain in experimental autoimmune encephalomyelitis.

Autor: Maguire AD; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2E1, Canada., Friedman TN; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2E1, Canada., Villarreal Andrade DN; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2E1, Canada., Haq F; Department of Anesthesiology and Pain Medicine, University of Alberta, Clinical Sciences Building, 2-150, Edmonton, AB, T6G 2G3, Canada., Dunn J; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2E1, Canada., Pfeifle K; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2E1, Canada., Tenorio G; Department of Anesthesiology and Pain Medicine, University of Alberta, Clinical Sciences Building, 2-150, Edmonton, AB, T6G 2G3, Canada., Buro K; Department of Mathematics and Statistics, MacEwan University, Edmonton, AB, T5J 2P2, Canada., Plemel JR; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2E1, Canada., Kerr BJ; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2E1, Canada. bradley.kerr@ualberta.ca.; Department of Pharmacology, University of Alberta, Edmonton, AB, T6E 2H7, Canada. bradley.kerr@ualberta.ca.; Department of Anesthesiology and Pain Medicine, University of Alberta, Clinical Sciences Building, 2-150, Edmonton, AB, T6G 2G3, Canada. bradley.kerr@ualberta.ca.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Dec 05; Vol. 12 (1), pp. 20995. Date of Electronic Publication: 2022 Dec 05.
DOI: 10.1038/s41598-022-25295-y
Abstrakt: Multiple Sclerosis (MS) is an autoimmune disease with notable sex differences. Women are not only more likely to develop MS but are also more likely than men to experience neuropathic pain in the disease. It has been postulated that neuropathic pain in MS can originate in the peripheral nervous system at the level of the dorsal root ganglia (DRG), which houses primary pain sensing neurons (nociceptors). These nociceptors become hyperexcitable in response to inflammation, leading to peripheral sensitization and eventually central sensitization, which maintains pain long-term. The mouse model experimental autoimmune encephalomyelitis (EAE) is a good model for human MS as it replicates classic MS symptoms including pain. Using EAE mice as well as naïve primary mouse DRG neurons cultured in vitro, we sought to characterize sex differences, specifically in peripheral sensory neurons. We found sex differences in the inflammatory profile of the EAE DRG, and in the TNFα downstream signaling pathways activated intracellularly in cultured nociceptors. We also found increased cell death with TNFα treatment. Given that TNFα signaling has been shown to initiate intrinsic apoptosis through mitochondrial disruption, this led us to investigate sex differences in the mitochondria's response to TNFα. Our results demonstrate that male sensory neurons are more sensitive to mitochondrial stress, making them prone to neuronal injury. In contrast, female sensory neurons appear to be more resistant to mitochondrial stress and exhibit an inflammatory and regenerative phenotype that may underlie greater nociceptor hyperexcitability and pain. Understanding these sex differences at the level of the primary sensory neuron is an important first step in our eventual goal of developing sex-specific treatments to halt pain development in the periphery before central sensitization is established.
(© 2022. The Author(s).)
Databáze: MEDLINE
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