Descending antinociceptive mechanisms in the brainstem: their role in the animal's defensive system.

The identification of specialized mechanisms in the mammalian brainstem that function to inhibit the rostral transmission of nociceptive (pain-related) information in the spinal cord led to an explosion of research into the neuroanatomical and neurochemical substrates of these antinociceptive systems. As outlined in the present paper, most attention was directed at those mechanisms in the periaqueductal grey (PAG) and rostral ventromedial medulla (RVM). However, comparatively little attention has been paid to the functional role of these mechanisms in animal behaviour. The purpose of the present paper is to review research into the behavioural significance of those antinociceptive mechanisms in the PAG and RVM. It is concluded that these mechanisms function as part of the animal's fear or defensive system, serving to make a threatened animal insensitive to noxious stimulation and thereby allowing that animal to engage in defensive responses instead of recuperative activities. Further, it is argued that the organization of these antinociceptive circuits reflects the animal's increasing capacity for early detection of danger. Specifically, nociception itself is held to signify the presence of immediate threat, and consequently, nociceptive input directly activates antinociceptive circuits at either the spinal level (during intense noxious stimulation) or RVM (following exposure to moderate noxious stimuli). In contrast, events that are themselves innocuous but which signal threat (either learned or innate danger signals) activate fear and defensive systems in the amygdala and PAG which engage the descending antinociceptive projections in the RVM.