Temporal filtering of nociceptive information by dynamic activation of endogenous pain modulatory systems

Endogenous pain control mechanisms have long been known to produce analgesia during "flight or fight" situations and to contribute to cognitively driven pain modulation, such as placebo analgesia. Afferent nociceptive information can also directly activate supraspinal descending modulatory systems, suggesting that these mechanisms may participate in feedback loops that dynamically alter the processing of nociceptive information. The functional significance of these feedback loops, however, remains unclear. The phenomenon of offset analgesia -- disproportionately large decreases in pain ratings evoked by small decreases in stimulus intensity -- suggests that dynamic activation of endogenous pain inhibition may contribute to the temporal filtering of nociceptive information. The neural mechanisms that mediate this phenomenon remain currently unknown. Using functional magnetic resonance imaging, we show that several regions of the midbrain and brainstem are differentially activated during offset analgesia. These activations are consistent with the location of areas such as the periaqueductal gray (PAG), rostral ventral medulla, and locus ceruleus that have substantial roles in descending inhibition of pain. This transient analgesia contributes to the temporal filtering of nociceptive information by producing a perceptual amplification of the magnitude and duration of decreases in noxious stimulus intensity. Together with the involvement of PAG and associated brainstem mechanisms in cognitively generated analgesia, the present observations suggest that the fundamental role of endogenous pain modulatory mechanisms is to dynamically shape the processing of nociceptive signals to best fit with the ever-changing demands of the environment.