Population Level Profiling of Primary Afferent Neuronal Activity in Response to Epinephrine Using Two-Photon Calcium Imaging

Stress in the face of overwhelming danger triggers activation of the sympathetic nervous system and leads to systemic release of epinephrine. Engagement of this system and the release of epinephrine can suppress incoming noxious information to allow for escape and survival from potentially threatening situations. However, the degree to which circulating epinephrine alters the activity of primary afferents is not known. Moreover, it is not clear whether epinephrine differentially modulates distinct subtypes of afferents and, if so, which ones. Here, we use two photon calcium imaging and the semi intact ex vivo preparation to characterize the effects of epinephrine on the responses of primary afferents to natural stimulation at the population level. This preparation involves dissecting in continuum intact skin of the hind limb with associated peripheral nerves, dorsal root ganglia, dorsal roots, and the spinal cord. Using this technique, we visualize the activity of all primary afferent subtypes simultaneously while distinguishing distinct subtypes using a novel method of pharmacological profiling. Collectively, these studies shed light on how distinct primary afferent populations are modulated by sympathetic tone and ultimately contribute to stress induced analgesia. Supported by T32NS073548 to HJS, R01AR063772, R01NS096705 to SER and HRK, and RM1NS128775 to HRK.