The role of the anterior pretectal nucleus in pain modulation: A comprehensive review

Abstract Descending pain modulation involves multiple encephalic sites and pathways that range from the cerebral cortex to the spinal cord. Behavioral studies conducted in the 1980s revealed that electrical stimulation of the pretectal area causes antinociception dissociation from aversive responses. Anatomical and physiological studies identified the anterior pretectal nucleus and its descending projections to several midbrain, pontine, and medullary structures. The anterior pretectal nucleus is morphologically divided into a dorsal part that contains a dense neuron population ( pars compacta ) and a ventral part that contains a dense fiber band network ( pars reticulata ). Connections of the two anterior pretectal nucleus parts are broad and include prominent projections to and from major encephalic systems associated with somatosensory processes. Since the first observation that acute or chronic noxious stimuli activate the anterior pretectal nucleus, it has been established that numerous mediators participate in this response through distinct pathways. Recent studies have confirmed that at least two pain inhibitory pathways are activated from the anterior pretectal nucleus. This review focuses on rodent anatomical, behavioral, molecular, and neurochemical data that have helped to identify mediators of the anterior pretectal nucleus and pathways related to its role in pain modulation.