title: Functional brain activation during retrieval of visceral pain-conditioned passive avoidance in the rat.
abstract: This study assessed functional brain activation in rats during expectation of visceral pain. Male rats were trained in step-down passive avoidance (PA) for 2 days. Upon stepping down from a platform, conditioned animals received noxious colorectal distension delivered through a colorectal balloon, whereas the balloon in control rats remained uninflated. On day 3, PA behavior was assessed while [(14)C]-iodoantipyrine was infused intravenously, followed by immediate euthanasia. Regional cerebral blood flow-related tissue radioactivity (rCBF) was analyzed by statistical parametric mapping using 3-dimensional brains reconstructed from autoradiographic brain slice images. Associated with retrieved PA behavior, conditioned rats compared with control subjects showed increases in rCBF in sensory (anterior insula, somatosensory cortex), limbic/paralimbic regions (anterior cingulate, prelimbic cortex, amygdala), all regions previously reported to show activation during acute visceral pain. Increases in rCBF were also noted in the dorsal hippocampus, nucleus accumbens, and caudate putamen, regions associated with retrieval of PA. Organization of the underlying brain network was further delineated by functional connectivity analysis. This revealed in conditioned rats a strongly and positively connected corticostriatal cluster (cingulate, prelimbic cortex, caudate putamen). The amygdala and cerebellar hemispheres formed another positively connected cluster, which was negatively connected with the corticostriatal cluster, suggesting corticolimbic modulation. Prelimbic cortex, nucleus accumbens, and anterior insula emerged in conditioned animals as hubs. Our results show that during retrieval of PA, brain areas implicated in PA expression as well as those implicated in acute visceral pain processing were recruited, in line with findings from human brain imaging studies on pain expectation.
authors.affiliation: Center for the Neurobiology of Stress, Department of Medicine, University of California, Los Angeles, CA, USA Department of Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, CA, USA Veterans Administration, Greater Los Angeles Healthcare System, Los Angeles, CA, USA Department of Chemistry and Biochemistry, California State University, Los Angeles, CA, USA Program in Neuroscience, University of Southern California, Los Angeles, CA, USA Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA Departments of Physiology, Psychiatry and Biobehavioral Sciences, Brain Research Institute, University of California, Los Angeles, CA, USA Departments of Cell and Neurobiology, Neurology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bradesi
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Charles
authors.forename: Raina D
authors.initials: RD
authors.lastname: Pang
authors.forename: Jean-Michel I
authors.initials: JI
authors.lastname: Maarek
authors.forename: Emeran A
authors.initials: EA
authors.lastname: Mayer
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Holschneider
mesh_terms: D000818:Animals; D001345:Autoradiography; D001362:Avoidance Learning / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D003214:Conditioning, Classical; D004195:Disease Models, Animal; D008297:Male; D008568:Memory / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D059265:Visceral Pain / Q000503:physiopathology* / Q000523:psychology