Population Imaging of Central Sensitization

Abstract

Capsaicin applied locally to the skin causes central sensitization that results in allodynia, a state in which pain is elicited by innocuous stimuli. Here, we used two-photon calcium imaging of neurons in the dorsal spinal cord to visualize central sensitization across excitatory interneurons and spinal projection neurons. To distinguish among excitatory neuron subtypes, we developed CICADA, a cell profiling approach that leverages the expression of distinct Gq-coupled receptors. We then identified capsaicin-responsive and capsaicin-sensitized neuronal populations. Capsaicin-sensitized neurons showed emergent responses to low threshold input and increased receptive field sizes consistent with the psychophysical phenomenon that allodynia is observed across an extended secondary zone. Finally, we identified spinal projection neurons that showed a shift in tuning toward low threshold input. These experiments provide a population-level view of central sensitization and a framework with which to model somatosensory integration in the dorsal horn. Grant support from NINDS.