title: Functional MRI of the Reserpine-Induced Putative Rat Model of Fibromyalgia Reveals Discriminatory Patterns of Functional Augmentation to Acute Nociceptive Stimuli.
abstract: Functional neuroimaging, applied to pre-clinical models of chronic pain, offers unique advantages in the drive to discover new treatments for this prevalent and oppressive condition. The high spatial and temporal resolution of fMRI affords detailed mapping of regional pharmacodynamics that underlie mechanisms of pain suppression by new analgesics. Despite evidence supporting the translational relevance of this approach, relatively few studies have investigated fMRI abnormalities in rodent models of chronic pain. In this study, we used fMRI to map the BOLD response in a recently developed putative rat model of fibromyalgia to innocuous and acute nociceptive stimuli by applying a step-wise graded electrical forepaw stimulation paradigm, with comparison to healthy controls. We observed discriminatory functional signatures (p < 0.001) to 2 mA electrical forepaw stimulation, found to be innocuous in the control group. As such, this translational approach provides sensitive and quantitative neural correlates of the underlying chronic disease. The regional patterns of functional augmentation were found to be concordant with previous studies of nociception in the anaesthetised rat brain, supporting the specificity of this approach in the study of altered central pain processing in reserpine induced myalgia. The methodology introduced in this work represents a novel platform for emerging treatment evaluation in highly experimentally controlled conditions.
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, QST, Chiba, Japan.|UCL Centre for Advanced Biomedical Imaging, University College London, UK.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Wells
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, QST, Chiba, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, QST, Chiba, Japan.|Drug Discovery Research, Astellas Pharma Inc., Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Fujikawa
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, QST, Chiba, Japan.|Drug Discovery Research, Astellas Pharma Inc., Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, QST, Chiba, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Saga
authors.affiliation: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, QST, Chiba, Japan.
authors.forename: Ichio
authors.initials: I
authors.lastname: Aoki
mesh_terms: D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D001931:Brain Mapping; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005356:Fibromyalgia / Q000139:chemically induced / Q000503:physiopathology*; D005552:Forelimb; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats; D012110:Reserpine
chemical_list: D001679:Biogenic Amines; D012110:Reserpine