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The description of multiple classes of opioid receptors has had a major impact on our understanding of the mechanisms of analgesia. Three major classes of opioid receptors have been defined: mu, kappa, and delta. The mu receptors have been further subclassified into two distinct subtypes (mu1 and mu2), as have the delta receptors (delta1 and delta2). Kappa receptors have been subdivided into kappa1, kappa2, or kappa3 subtypes. All of these subtypes modulate pain perception, with the exception of the kappa2 receptor, which has not been adequately examined. Supraspinal systems have been described for mu1, kappa3, and delta2 receptors while mu2, kappa1, and delta1 receptors modulate pain at the spinal level. In addition to their ability to act independently, the various systems also interact synergistically with each other. Thus, the relief of pain involves the complex interaction of at least six receptor systems. This review discusses the implications of opiate receptor multiplicity on the control of pain.