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The gate control theory's most important contribution to understanding pain was its emphasis on central neural mechanisms. The theory forced the medical and biological sciences to accept the brain as an active system that filters, selects and modulates inputs. The dorsal horns, too, were not merely passive transmission stations but sites at which dynamic activities (inhibition, excitation and modulation) occurred. The great challenge ahead of us is to understand brain function. I have therefore proposed that the brain possesses a neural network--the body-self neuromatrix--which integrates multiple inputs to produce the output pattern that evokes pain. The body-self neuromatrix comprises a widely distributed neural network that includes parallel somatosensory, limbic and thalamocortical components that subserve the sensory-discriminative. affective-motivational and evaluative-cognitive dimensions of pain experience. The synaptic architecture of the neuromatrix is determined by genetic and sensory influences. The 'neurosignature' output of the neuromatrix--patterns of nerve impulses of varying temporal and spatial dimensions--is produced by neural programs genetically build into the neuromatrix and determines the particular qualities and other properties of the pain experience and behavior. Multiple inputs that act on the neuromatrix programs and contribute to the output neurosignature include. (1) sensory inputs (cutaneous, visceral and other somatic receptors); (2) visual and other sensory inputs that influence the cognitive interpretation of the situation; (3) phasic and tonic cognitive and emotional inputs from other areas of the brain; (4) intrinsic neural inhibitory modulation inherent in all brain function; (5) the activity of the body's stress-regulation systems, including cytokines as well as the endocrine, autonomic, immune and opioid systems. We have traveled a long way from the psychophysical concept that seeks a simple one-to-one relationship between injury and pain. We now have a theoretical framework in which a genetically determined template for the body-self is modulated by the powerful stress system and the cognitive functions of the brain, in addition to the traditional sensory inputs.