Noxious activation of spinal or vagal afferents evokes distinct patterns of fos-like immunoreactivity in the ventrolateral periaqueductal gray of unanaesthetised rats.

The consequences of a severe traumatic injury--deep pain and haemorrhage--usually evoke a passive emotional coping reaction characterised by: quiescence and immobility, decreased vigilance, hypotension and bradycardia. Results of studies utilising microinjections of excitatory amino acids suggest that passive coping reactions are mediated, at least in part, by activation of the midbrain, ventrolateral periaqueductal gray (vlPAG) region. Further, experiments in anaesthetised rats, using the expression of the immediate-early gene, c-fos, as a marker of neuronal activation, report that pain arising from muscles, joints or viscera selectively activates the vlPAG. Anaesthesia alone, however, evokes substantial Fos-like immunoreactivity (IR) within the vlPAG and this may have obscured any differences in patterns of Fos expression following noxious deep somatic versus noxious visceral activation. In these experiments, in unanaesthetised rats, the effects of noxious spinal versus noxious vagal primary afferent activation were re-examined and distinct rostrocaudal patterns of Fos-expression were observed. Specifically: (i) injection of algesic substances into muscle, which preferentially activates spinal afferents, evoked Fos expression predominantly within the caudal vlPAG; whereas, (ii) noxious manipulations whose effects are mediated by (cardiopulmonary) vagal activation evoked preferential Fos-expression within the rostral vlPAG. On the other hand, hypotensive haemorrhage evoked substantial Fos expression along the entire rostrocaudal extent of the vlPAG, a finding which fits with suggestions that haemorrhagic shock is triggered by a combination of: (i) spinally-relayed nociceptive signals originating from ischaemic tissue, and (ii) vagally-relayed signals reflecting poor cardiac filling.