title: Mapping of pain circuitry in early post-natal development using manganese-enhanced MRI in rats.
abstract: Premature or ill full-term infants are subject to a number of noxious procedures as part of their necessary medical care. Although we know that human infants show neural changes in response to such procedures, we know little of the sensory or affective brain circuitry activated by pain. In rodent models, the focus has been on spinal cord and, more recently, midbrain and medulla. The present study assesses activation of brain circuits using manganese-enhanced magnetic resonance imaging (MEMRI). Uptake of manganese, a paramagnetic contrast agent that is transported across active synapses and along axons, was measured in response to a hindpaw injection of dilute formalin in 12-day-old rat pups, the age at which rats begin to show aversion learning and which is roughly the equivalent of full-term human infants. Formalin induced the oft-reported biphasic response at this age and induced a conditioned aversion to cues associated with its injection, thus demonstrating the aversiveness of the stimulation. Morphometric analyses, structural equation modeling and co-expression analysis showed that limbic and sensory paths were activated, the most prominent of which were the prefrontal and anterior cingulate cortices, nucleus accumbens, amygdala, hypothalamus, several brainstem structures, and the cerebellum. Therefore, both sensory and affective circuits, which are activated by pain in the adult, can also be activated by noxious stimulation in 12-day-old rat pups.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, United States.
authors.forename: M M
authors.initials: MM
authors.lastname: Sperry
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, United States.
authors.forename: B M
authors.initials: BM
authors.lastname: Kandel
authors.affiliation: NMR Core, Children's Hospital of Philadelphia, United States.
authors.forename: S
authors.initials: S
authors.lastname: Wehrli
authors.affiliation: Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, United States.
authors.forename: K N
authors.initials: KN
authors.lastname: Bass
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, United States.
authors.forename: S R
authors.initials: SR
authors.lastname: Das
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, United States.
authors.forename: P S
authors.initials: PS
authors.lastname: Dhillon
authors.affiliation: Penn Image Computing and Science Laboratory, Department of Radiology, University of Pennsylvania, United States.
authors.forename: J C
authors.initials: JC
authors.lastname: Gee
authors.affiliation: Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, United States. Electronic address: barrg@email.chop.edu.
authors.forename: G A
authors.initials: GA
authors.lastname: Barr
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000000981:diagnostic imaging* / Q000254:growth & development*; D001931:Brain Mapping; D002712:Chlorides / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005557:Formaldehyde / Q000633:toxicity; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D017895:Manganese Compounds / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000473:pathology*; D010147:Pain Measurement; D051381:Rats; D013997:Time Factors
chemical_list: D002712:Chlorides; D017895:Manganese Compounds; D005557:Formaldehyde; C025340:manganese chloride
keywords: MRI; brain; circuitry; development; nociception