Spinal sources of noxious visceral and noxious deep somatic afferent drive onto the ventrolateral periaqueductal gray of the rat

Abstract

Studies utilizing the expression of Fos protein as a marker of neuronal activation have revealed that pain of deep somatic or visceral origin selectively activates the ventrolateral periaqueductal gray (vlPAG). Previous anatomical tracing studies revealed that spinal afferents to the vlPAG arose from the superficial and deep dorsal horn and nucleus of the dorsolateral funiculus at all spinal segmental levels, with approximately 50% of vlPAG-projecting spinal neurons found within the upper cervical spinal cord. This study utilized detection of Fos protein to determine the specific populations of vlPAG-projecting spinal neurons activated by noxious deep somatic or noxious visceral stimulation. Pain of cardiac or peritoneal (i.e., visceral) origin activated neurons in the superficial and deep dorsal horn and nucleus of the dorsolateral funiculus of the thoracic cord, whereas pain of hindlimb (i.e., deep somatic) origin activated neurons in the same laminar regions but in the lumbosacral cord. Each of these deep noxious manipulations also activated neurons in the superficial and deep dorsal horn and nucleus of the dorsolateral funiculus of the upper cervical spinal cord. In a second set of experiments, the combination of retrograde tracing and Fos immunohistochemistry revealed that vlPAG-projecting spinal neurons activated by deep somatic pain were located in both the upper cervical and lumbosacral cord, whereas those activated by visceral pain were restricted to the thoracic spinal cord. Thus pain arising from visceral versus deep somatic body regions influences neural activity within the vlPAG via distinct spinal pathways. The findings also highlight the potential significance of the upper cervical cord in integrating pain arising from deep structures throughout the body.