Different representations of inescapable noxious stimuli in the periaqueductal gray and upper cervical spinal cord of freely moving rats.

Previous work suggested that pain of distinct tissue origins was differentially represented in the midbrain periaqueductal gray (PAG). That is, persistent pain of deep origin (muscle, joint viscera) "activated" ventrolateral PAG neurons and triggered quiescence, hyporeactivity and vasodepression (i.e. passive emotional coping); whereas intermittent cutaneous pain "activated" lateral PAG neurons and triggered fight-flight (i.e. active emotional coping). Cutaneous noxious stimuli, if inescapable however, trigger a passive emotional coping reaction similar to that evoked by pain of deep origin. This raised the question--is it the behavioural significance (escapability versus inescapability) or the tissue origin (cutaneous versus deep) of the pain, that is represented in the PAG? In this study we used immediate-early-gene (c-Fos) expression to examine PAG and spinal activation patterns following "inescapable" (persistent) pain of cutaneous versus deep origin. It was found that selective activation of the ventrolateral PAG and passive emotional coping were evoked by an inescapable cutaneous noxious stimulus (i.e. clip of the neck), as well as by a deep noxious stimulus (i.e. neck muscle pain). In the upper cervical spinal cord, however, these noxious manipulations evoked distinct patterns of Fos expression which reflected the different patterns of primary afferent termination arising from skin versus muscle. The results suggest that whereas pain representation in the spinal cord accurately reflects tissue origin, pain representation in the PAG better reflects behavioural significance.