title: Colonic inflammation induces fos expression in the thoracolumbar spinal cord increasing activity in the spinoparabrachial pathway.
abstract: The descending colon and rectum are innervated by primary afferent fibers projecting to the lumbosacral and thoracolumbar spinal cord segments. Previous work from this laboratory has suggested that afferent input and sensory processing in the lumbosacral spinal cord is necessary and sufficient to mediate reflex responses to transient colorectal stimulation while processing in both the lumbosacral and thoracolumbar spinal cord segments contribute to visceral hyperalgesia. In the rat, repetitive noxious colorectal distention (CRD) induces >200 Fos labeled cells per section in the lumbosacral segments, but few in the thoracolumbar segments, further suggesting that transient colonic nociceptive input is transduced primarily in the lumbosacral spinal cord. The laminar distribution of this CRD-induced Fos suggests some of these neurons project to the parabrachial nucleus (PBn), an important relay for visceroceptive input from the spinal cord to higher order centers for nociceptive processing. In this study, two hypotheses were tested: first, inflammation of the colon prior to CRD would induce Fos expression in neurons in the thoracolumbar spinal cord segments and increase the number of neurons in the lumbosacral spinal cord segments that express Fos in response to noxious CRD; and second, the inflammation-induced increase in Fos expression in the spinal cord would be partially manifest as an increase in the number of spinoparabrachial projection neurons that respond to CRD. The retrograde tracer Fluorogold (FG) was injected unilaterally into the PBn of male Sprague-Dawley rats. Ten to 14 days later the rat's colon was either distended or inflamed and distended. Sections from the T13-L2 and L6-S2 spinal cord segments were double labeled using antibodies directed against FG and Fos protein. The results show that: (1) colonic inflammation plus distention induced Fos expression in the thoracolumbar spinal cord and increased Fos expression in the lumbosacral spinal cord compared to distention alone. In the lumbosacral cord, the increase in Fos expression was localized primarily to the superficial dorsal horn (SDH). In the thoracolumbar spinal segments, Fos was induced primarily in the SDH and the area around the central canal. (2) Injection of FG into the PBn produced dense retrograde labeling in the SDH, the lateral deeper gray matter and the area around the central canal at the lumbosacral and thoracolumbar levels. (3) In the lumbosacral spinal cord, 30-40% of the FG labeled cells double labeled for Fos. Colonic inflammation plus CRD did not significantly increase the percentage of spinoparabrachial neurons that were labeled for Fos compared to distention alone. (4) In the thoracolumbar spinal cord less than 10% of the FG labeled neurons were double labeled for Fos following CRD, but 25% of the FG labeled neurons in the SDH were double labeled following colonic inflammation. These data support the hypothesis that colonic inflammation activates viscerosensory processing in the thoracolumbar spinal cord and further suggests that this information is relayed to the PBn. The increase in information reaching the PBn over these parallel pathways may contribute to the affective-motivational component of the pain experience.
authors.affiliation: Department of Oral and Craniofacial Biological Sciences, Dental School, University of Maryland, 666 W. Baltimore Street, Baltimore, MD 21201, USA. rjt001@dental.umaryland.edu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Traub
authors.forename: Anne
authors.initials: A
authors.lastname: Murphy
mesh_terms: D000818:Animals; D003092:Colitis / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D013904:Thoracic Vertebrae / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos