Deep and superficial noxious stimulation increases Fos-like immunoreactivity in different regions of the midbrain periaqueductal grey of the rat

Abstract

We have reported that the lateral region of the caudal third of the midbrain periaqueductal grey (PAG), which mediates flight and hypertension, receives inputs from lamina I and IIo and the lateral cervical nucleus (LCN) of the upper cervical spinal cord (UCC); whereas the ventrolateral PAG region, which mediates hypotension, quiescence and immobility, is targeted by cells in laminae VII, VIII and X. In the UCC the cells of laminae VII and VIII receive a significant afferent input from the deep neck muscles, whereas cells of laminae I and IIo and the LCN receive a large input from cutaneous nociceptors. Thus we investigated the hypothesis that nociceptive activation of the deep neck muscles would activate the spinal-ventrolateral PAG projection, whereas cutaneous nociceptive stimulation would activate the spinal-lateral PAG projection, by examining the expression of Fos protein. We found that deep noxious stimulation led to Fos-positive cells predominantly in the ventrolateral PAG and superficial noxious stimulation led to Fos-positive cells predominantly in the lateral PAG. The results: (i) indicate that the UCC afferent regulation of the PAG arises from topographically separable and functionally dissociable populations of neurons and (ii) raise the possibility that the ventrolateral and lateral PAG play important but different roles in mediating the distinctive affective, emotional and autonomic responses evoked by pain arising from deep or superficial structures.