Cell type-specific calcium imaging of central sensitization in mouse dorsal horn

Charles Warwick, Joseph Salsovic, Junichi Hachisuka, Kelly M. Smith, Tayler D. Sheahan, Haichao Chen, James Ibinson, H. Richard Koerber () and Sarah E. Ross ()
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Charles Warwick: University of Pittsburgh
Joseph Salsovic: University of Pittsburgh
Junichi Hachisuka: University of Pittsburgh
Kelly M. Smith: University of Pittsburgh
Tayler D. Sheahan: University of Pittsburgh
Haichao Chen: University of Pittsburgh
James Ibinson: University of Pittsburgh
H. Richard Koerber: University of Pittsburgh
Sarah E. Ross: University of Pittsburgh

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Allodynia is a state in which pain is elicited by innocuous stimuli. Capsaicin applied to the skin results in an allodynia that extends to a broad region beyond the application site. This sensitization is thought to be mediated by spinal networks; however, we do not have a clear picture of which spinal neurons mediate this phenomenon. To address this gap, we used two-photon calcium imaging of excitatory interneurons and spinal projection neurons in the mouse spinal dorsal horn. To distinguish among neuronal subtypes, we developed CICADA, a cell profiling approach to identify cell types during calcium imaging. We then identified capsaicin-responsive and capsaicin-sensitized neuronal populations. Capsaicin-sensitized neurons showed emergent responses to innocuous input and increased receptive field sizes consistent with psychophysical reports. Finally, we identified spinal output neurons that showed enhanced responses from innocuous input. These experiments provide a population-level view of central sensitization and a framework with which to model somatosensory integration in the dorsal horn.

Date: 2022
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DOI: 10.1038/s41467-022-32608-2

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