A key question in this topical workshop is whether basic mechanisms being defined for spontaneous activity in nociceptors have useful clinical implications. Spontaneous activity in primary somatosensory neurons has long been associated with non-evoked pain, but the underlying mechanisms have been slow to emerge. However, recent advances have identified electrophysiological and cellular mechanisms of spontaneous activity in rodent and human nociceptors that make therapeutically promising predictions that can be tested in human patients. Dr. Carolina Roza will summarize aberrant electrophysiological behavior of peripheral nerve fibers observed in experimental models, the associated pathophysiological mechanisms, and their relationship to symptoms reported by patients. Dr. Edgar Walters will describe newly characterized irregular depolarizing spontaneous fluctuations of membrane potential in dissociated rodent and human nociceptors that drive spontaneous activity, how these synergize with other electrophysiological alterations that promote ongoing discharge, and the identification of prominent underlying biophysical and cell signaling alterations. Dr. Martin Schmelz will show microneurographic evidence for depolarization of spontaneously active nociceptors in patients and describe how the effects of slow depolarizing electrical stimuli applied to human and pig nociceptors are consistent with new findings from rodent nociceptors, potentially providing improved translational tools to assess alterations of nociceptor excitability in patients.