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Animal and genetic research, recent developments of nonpeptide substance P antagonists, and important changes in the understanding of neurotransmission have each contributed to the current understanding of substance P. After 7 decades, the physiologic role of substance P is known as a modulator of nociception, involved in signaling the intensity of noxious or aversive stimuli. Genetic studies in mice and development of substance P antagonists provide more recent results that support the redefinition of the central role of substance P. 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