cluster firing data qz.xlsx

Spontaneous pain refers to pain occurring without external stimuli. It is a primarycomplaint in chronic pain conditions and remains difficult to treat. Moreover, themechanisms underlying spontaneous pain remain poorly understood. Here, weemployed in vivo imaging of dorsal root ganglion (DRG) neurons and discovered adistinct form of abnormal spontaneous activity following peripheral nerve injury:clusters of adjacent DRG neurons firing synchronously and sporadically. The level ofcluster firing directly correlated with nerve injury induced spontaneous pain behaviors.Furthermore, we demonstrated that cluster firing is triggered by activity of sympatheticnerves, which sprout into DRG after injury, and identified norepinephrine as a keyneurotransmitter mediating this unique firing. Chemogenetic and pharmacologicalmanipulations of sympathetic activity and norepinephrine receptors suggest that theyare both necessary and sufficient for DRG cluster firing and spontaneous painbehavior. Therefore, blocking sympathetic-mediated cluster firing may represent a newparadigm in treating spontaneous pain.