Central nervous system (CNS) mechanisms of pain processing do not consist only of a bottom-up process whereby a painful focus modifies the inputs to the next higher level. In fact, the brain has many strategies to modify information that it receives; pain sensations are not merely conscious replicas of the inputs that reach the CNS. Selection is the main mechanism that generates a pain sensation and thus by modulatory mechanisms, the brain can modify the efficacy of nociceptive inputs. The article in the present issue by King et al.[6], explores diffuse noxious inhibitory control (DNIC) in chronic pain patients, and is an example of building bridges between preclinical and clinical research at its best. The central finding of this study is that significant reductions in the strength of DNIC are detected in both irritable-bowel syndrome and temporomandibular disorder patients. Of particular interest is the methodology used, including individualized temperatures for conditioning and conditioned stimuli that allowed the authors to provide data demonstrating clear differences between healthy subjects and chronic pain patients. These observations led the authors to suggest that a reduced ability to inhibit pain in patients with chronic pain is probably mediated by a dysfunction of endogenous pain inhibitory systems.

Since the pioneer work of Le Bars and colleagues [7], which demonstrated that DNIC can induce widespread inhibitory controls on rat deep dorsal horn neurons, the question has remained whether DNIC is more than just a laboratory curiosity. Indeed, subsequent studies showed that these controls have common anatomical and functional features in animals and humans. The supraspinal structures responsible for DNIC include the subnucleus reticularis dorsalis (SRD) in the caudal-dorsal medulla, which contains a homogeneous population of neurons whose properties mirror the functional characteristics of DNIC, viz. they are activated exclusively by noxious stimuli applied to any region of the body and precisely encode the intensity of these stimuli [9]. Moreover, lesions of the caudal medulla reduce DNIC in both animals and humans [3]. These caudal medullary networks have been proposed to facilitate the extraction of nociceptive information by increasing the signal-to-noise ratio between a pool of deep dorsal horn neurons that are activated from a painful focus and the remaining population of such neurons, which are simultaneously inhibited. Other studies also suggested that DNIC mediates the ‘pain inhibits pain’or ‘counter-stimulation’phenomenon, whereby there is a mutual inhibition between the pathways that generate sensations elicited concomitantly by two separate painful foci. In addition, DNIC also inhibits lamina I neurons, a key relay for nociceptive inputs to CNS areas that process signals relevant to homeostasis [2]. This suggests that a broader modulatory role is exerted by DNIC, probably