Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2021 Dec 2:10:e74935.
doi: 10.7554/eLife.74935.

Why sex matters

Josette J Wlaschin  1   2 , Sangeetha Hareendran  1 , Claire E Le Pichon  1
Affiliations
Comment

Why sex matters

Josette J Wlaschin et al. Elife. .

Abstract

The immune mechanisms underlying hypersensitivity to pain after nerve injury are different in male and female mice.

Keywords: CSF1; Treg; meninges; microglia; mouse; neuroscience; pain; spinal cord.

PubMed Disclaimer

Conflict of interest statement

JW, SH, CL No competing interests declared

Figures

Figure 1.
Figure 1.. The differing effects of CSF1 injection on male and female mice.
When CSF1 is injected into wild-type mice, microglia in the spinal cord become activated (red cells) in male mice (top) but not females (middle). In females, regulatory T-cells (Tregs, blue circles) present in the membrane layers surrounding the spinal cord block CSF1 from activating microglia, which remain in the resting state (green cells); when regulatory T-cells are depleted (Treg KO; bottom), the microglia of female mice respond to CSF1 the same way as in males (bottom). During Von Frey pain assessment tests, female mice with depleted levels of regulatory T-cells and male mice exhibit the paw withdrawal response typical of hypersensitivity (top and bottom); however, female mice do not elicit a hypersensitive pain response. This indicates that regulatory T-cells suppress the activation of microglia and development of a pain response after CSF1 injection, but only in female mice.
See this image and copyright information in PMC

Comment on

References

    1. Calvo M, Dawes JM, Bennett DLH. The role of the immune system in the generation of neuropathic pain. The Lancet. Neurology. 2012;11:629–642. doi: 10.1016/S1474-4422(12)70134-5. - DOI - PubMed
    1. Decosterd I, Woolf CJ. Spared nerve injury: an animal model of persistent peripheral neuropathic pain. Pain. 2000;87:149–158. doi: 10.1016/S0304-3959(00)00276-1. - DOI - PubMed
    1. Guan Z, Kuhn JA, Wang X, Colquitt B, Solorzano C, Vaman S, Guan AK, Evans-Reinsch Z, Braz J, Devor M, Abboud-Werner SL, Lanier LL, Lomvardas S, Basbaum AI. Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain. Nature Neuroscience. 2016;19:94–101. doi: 10.1038/nn.4189. - DOI - PMC - PubMed
    1. Kuhn JA, Vainchtein ID, Braz J, Hamel K, Bernstein M, Craik V, Dahlgren MW, Ortiz-Carpena J, Molofsky AB, Molofsky AV, Basbaum AI. Regulatory T-cells inhibit microglia-induced pain hypersensitivity in female mice. eLife. 2021;10:e69056. doi: 10.7554/eLife.69056. - DOI - PMC - PubMed
    1. Mogil JS. Qualitative sex differences in pain processing: emerging evidence of a biased literature. Nature Reviews. Neuroscience. 2020;21:353–365. doi: 10.1038/s41583-020-0310-6. - DOI - PubMed