Sex differences in peripheral immune cell activation: Implications for pain and pain resolution.

Autor: Friedman TN; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada., La Caprara O; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada., Zhang C; Department of Pharmacology, University of Alberta, Edmonton, AB T6E 2H7, Canada., Lee K; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada., May J; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2S2, Canada., Faig CA; Department of Pharmacology, University of Alberta, Edmonton, AB T6E 2H7, Canada., Baldwin T; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2S2, Canada., Plemel JR; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada., Taylor AMW; Department of Pharmacology, University of Alberta, Edmonton, AB T6E 2H7, Canada; Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada., Kerr BJ; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Pharmacology, University of Alberta, Edmonton, AB T6E 2H7, Canada; Department of Psychiatry (NRU), University of Alberta, Edmonton, AB T6G 2B7, Canada; Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada. Electronic address: bradley.kerr@ualberta.ca.
Jazyk: angličtina
Zdroj: Brain, behavior, and immunity [Brain Behav Immun] 2023 Nov; Vol. 114, pp. 80-93. Date of Electronic Publication: 2023 Aug 06.
DOI: 10.1016/j.bbi.2023.07.029
Abstrakt: Decades of research into chronic pain has deepened our understanding of the cellular mechanisms behind this process. However, a failure to consider the biological variable of sex has limited the application of these breakthroughs into clinical application. In the present study, we investigate fundamental differences in chronic pain between male and female mice resulting from inflammatory activation of the innate immune system. We provide evidence that female mice are more sensitive to the effects of macrophages. Injecting small volumes of media conditioned by either unstimulated macrophages or macrophages stimulated by the inflammatory molecule TNFα lead to increased pain sensitivity only in females. Interestingly, we find that TNFα conditioned media leads to a more rapid resolution of mechanical hypersensitivity and altered immune cell recruitment to sites of injury. Furthermore, male and female macrophages exhibit differential polarization characteristics and motility after TNFα stimulation, as well as a different profile of cytokine secretions. Finally, we find that the X-linked gene Tlr7 is critical in the facilitating the adaptive resolution of pain in models of acute and chronic inflammation in both sexes. Altogether, these findings suggest that although the cellular mechanisms of pain resolution may differ between the sexes, the study of these differences may yield more targeted approaches with clinical applications.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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