Trigeminal afferents sense locomotion-related meningeal deformations

Andrew S Blaeser; Arthur U Sugden; Jun Zhao; Simone Carneiro-Nascimento; Frederick B Shipley; Hanaé Carrié; Mark L Andermann; Dan Levy

doi:10.1016/j.celrep.2022.111648

Trigeminal afferents sense locomotion-related meningeal deformations

Cell Rep. 2022 Nov 15;41(7):111648. doi: 10.1016/j.celrep.2022.111648.

Authors

Andrew S Blaeser¹, Arthur U Sugden², Jun Zhao¹, Simone Carneiro-Nascimento¹, Frederick B Shipley², Hanaé Carrié², Mark L Andermann³, Dan Levy⁴

Affiliations

¹ Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
² Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
³ Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: manderma@bidmc.harvard.edu.
⁴ Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: dlevy1@bidmc.harvard.edu.

Abstract

The trigeminal sensory innervation of the cranial meninges is thought to serve a nociceptive function and mediate headache pain. However, the activity of meningeal afferents under natural conditions in awake animals remains unexplored. Here, we used two- and three-dimensional two-photon calcium imaging to track the activity of meningeal afferent fibers in awake mice. Surprisingly, a large subset of afferents was activated during non-noxious conditions such as locomotion. We estimated locomotion-related meningeal deformations and found afferents with distinct dynamics and tuning to various levels of meningeal expansion, compression, shearing, and Z-axis motion. Further, these mechanosensitive afferents were often tuned to distinct directions of meningeal expansion or compression. Thus, in addition to their role in headache-related pain, meningeal sensory neurons track the dynamic mechanical state of the meninges under natural conditions.

Keywords: CP: Neuroscience; locomotion; mechanosensitivity; meningeal deformation; meningeal sensory innervation; two-photon calcium imaging.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Headache
Locomotion
Meninges*
Mice
Neurons, Afferent* / physiology

Abstract

Publication types

MeSH terms

Grants and funding