The Neural Code for Pain: From Single-Cell Electrophysiology to the Dynamic Pain Connectome

Pain occurs in time. In naturalistic settings, pain perception is sometimes stable but often varies in intensity and quality over the course of seconds, minutes, and days. A principal aim in classic electrophysiology studies of pain was to uncover a neural code based on the temporal patterns of single neuron firing. In contrast, modern neuroimaging studies have placed emphasis on uncovering the spatial pattern of brain activity (or "map") that may reflect the pain experience. However, in the emerging field of connectomics, communication within and among brain networks is characterized as intrinsically dynamic on multiple time scales. In this review, we revisit the single-cell electrophysiological evidence for a nociceptive neural code and consider how those findings relate to recent advances in understanding systems-level dynamic processes that suggest the existence of a "dynamic pain connectome" as a spatiotemporal physiological signature of pain. We explore how spontaneous activity fluctuations in this dynamic system shape, and are shaped by, acute and chronic pain experiences and individual differences in those experiences. Highlighting the temporal dimension of pain, we aim to move pain theory beyond the concept of a static neurosignature and toward an ethologically relevant account of naturalistic dynamics.