The CPM Effect: Functional Assessment of the Diffuse Noxious Inhibitory Control in Humans

The diffuse noxious inhibitory control, which has been investigated extensively in animals, consists of the inhibitory modulation of pain pathways after heterotopic noxious stimulation. The subnucleus reticularis dorsalis, which lies in the caudal part of the medulla, together with its descending projections to the wide-dynamic-range neurones, is responsible for the diffuse noxious inhibitory control. Many studies have investigated the diffuse noxious inhibitory control phenomenon in humans. However, owing to the complexity of the effect of descending modulation on human pain perception, expert opinion has recommended the term "conditioned pain modulation" to describe the psychophysical paradigm in which a heterotopic noxious stimulus is used to affect pain pathways in humans. In this narrative review, we present the current knowledge on the mechanisms underlying the diffuse noxious inhibitory control in animals and show how this phenomenon can be investigated in humans by using the conditioned pain modulation paradigm. We also demonstrate the relevance of conditioned pain modulation to the pathophysiology of pain.