title: Metabolic plasticity in the supraspinal pain modulating circuitry after noxious stimulus-induced spinal cord LTP.
abstract: It has been suggested that spinal cord long-term potentiation (LTP) may contribute to hypersensitivity and hyperalgesia. We have investigated if noxious stimulus-induced spinal cord LTP might have a long lasting effect on supraspinal neuronal activity. First, we verified that spinal LTP was induced by electrical high frequency stimuli (HFS) conditioning applied to the sciatic nerve. The C-fibre response in the dorsal horn reached a twofold increase 150 min after HFS (t-test, p<0.01, n=6). Then, to study the metabolic supraspinal activity following the same stimulation protocol, we used small animal positron emission tomography (PET) and the glucose analog [(18)F]-fluorodeoxyglucose (FDG). With this combined approach we measured changes in regional supraspinal activity at two time points in HFS conditioned and in sham animals; acute (immediately after HFS/sham, n=4) and late phase (150 min after HFS/sham, n=10). Comparisons between HFS and sham groups revealed that induction of spinal LTP was followed by an acute metabolic response in the primary somatosensory cortex (S1), but also various slower metabolic adaptations in brain regions involved in modulation of nociceptive signaling and descending inhibition, i.e., amygdala, periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and the dorsolateral pontomesencephalic tegmentum (DLPT) (t-test, p<0.05). The study demonstrates that PET may be used as an in vivo method to study regional brain metabolic activity between different conditions. It is concluded that noxious sciatic stimuli which induce spinal cord LTP also affect supraspinal metabolic activity. We suggest that these changes might illustrate a supraspinal maladaptive dysfunction involved in pain hypersensitivity and hyperalgesia.
authors.affiliation: Centre for Molecular Biology and Neuroscience & Institute of Basic Medical Sciences, University of Oslo, Norway National Institute of Occupational Health, Norway Department of Molecular Biosciences, University of Oslo, Norway Department of Radiology, Aker University Hospital, Norway.
authors.forename: Trine
authors.initials: T
authors.lastname: Hjornevik
authors.forename: Line M
authors.initials: LM
authors.lastname: Jacobsen
authors.forename: Hong
authors.initials: H
authors.lastname: Qu
authors.forename: Jan G
authors.initials: JG
authors.lastname: Bjaalie
authors.forename: Johannes
authors.initials: J
authors.lastname: Gjerstad
authors.forename: Frode
authors.initials: F
authors.lastname: Willoch
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D001933:Brain Stem / Q000378:metabolism / Q000503:physiopathology; D004558:Electric Stimulation; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006930:Hyperalgesia / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology*; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology*; D010146:Pain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000503:physiopathology; D013003:Somatosensory Cortex / Q000378:metabolism / Q000503:physiopathology; D013116:Spinal Cord / Q000503:physiopathology*; D013995:Time
chemical_list: D019788:Fluorodeoxyglucose F18