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

• Published in: Nature communications 2022-09, Vol.13 (1), p.5199-5199, Article 5199
• Main Authors: Warwick, Charles, Salsovic, Joseph, Hachisuka, Junichi, Smith, Kelly M., Sheahan, Tayler D., Chen, Haichao, Ibinson, James, Koerber, H. Richard, Ross, Sarah E.
• Format: Article
• Language: English
• Subjects: 14/10; 14/19; 14/32; 14/34; 14/35; 14/63; 14/69; 631/378/2620/410/2610; 631/378/3917; 631/378/87; Animals; Calcium; Calcium - metabolism; Calcium imaging; Calcium ions; Capsaicin; Capsaicin - metabolism; Capsaicin - pharmacology; Central Nervous System Sensitization; Dorsal horn; Experiments; Horns; Humanities and Social Sciences; Hyperalgesia - metabolism; Imaging; Interneurons; Labeling; Mechanotransduction; Mice; multidisciplinary; Neurons; Neurosciences; Pain; Pain perception; Population; Populations; Posterior Horn Cells - metabolism; Psychophysics; Receptive field; Science; Science (multidisciplinary); Skin; Spinal cord; Spinal Cord Dorsal Horn
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32608-2

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. Altered mechanosensation by application of capsaicin to the skin is thought to be spinally mediated. Here, the authors use Ca2+ imaging in spinal neurons and develop a cell profiling approach to identify populations involved in central sensitization.