title: Functional brain mapping using specific sensory-circuit stimulation and a theoretical graph network analysis in mice with neuropathic allodynia.
abstract: Allodynia, a form of neuropathic pain, is defined as pain in response to a non-nociceptive stimulus. The brain regions responsible for pain, which are not normally activated, can be activated in allodynic mice by providing a suitable stimulus to Aβ-fibers, which transmit signals from tactile sensory fibers. Functional MRI (fMRI) can be used to objectively observe abnormal brain activation. In the present study, fMRI was conducted to investigate allodynia in mice; allodynia was generated by surgical injury at the L4 spinal nerve root, thus selectively stimulating sensory nerve fibers. In intact mice, only the primary somatosensory cortex (S1) was activated by stimulation of Aβ-fibers. Meanwhile, allodynic mice showed significantly higher BOLD signals in the anterior cingulate area (ACA) and thalamus. Using resting state fMRI, both degree and eigenvector centrality were significantly decreased in the contralateral S1, clustering coefficient and local efficiency were significantly increased in the ACA, and betweenness centrality was significantly higher in the ventral posterolateral nucleus of the thalamus. These results suggest that the observed abnormal BOLD activation is associated with defects in Aβ-fibers when Aβ-fibers in allodynic mice are selectively stimulated. The objective approach enabled by fMRI can improve our understanding of pathophysiological mechanisms and therapeutic efficacy.
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.|Imaging Analysis Laboratory, Laboratory Animal Research Department, Central Institute for Experimental Animals, Kawasaki-shi, Kanagawa 210-0821, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Komaki
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.|Imaging Analysis Laboratory, Laboratory Animal Research Department, Central Institute for Experimental Animals, Kawasaki-shi, Kanagawa 210-0821, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Hikishima
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.|Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Musashimurayama-shi, Tokyo 208-0011, Japan.
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Konomi
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.|Imaging Analysis Laboratory, Laboratory Animal Research Department, Central Institute for Experimental Animals, Kawasaki-shi, Kanagawa 210-0821, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Seki
authors.affiliation: Faculty of Radiological Technology, School of Health Sciences, Fujita Health University, Toyoake-shi, Aichi 470-1192, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku Tokyo 113-8519, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyasaka
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.|Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Musashimurayama-shi, Tokyo 208-0011, Japan.
authors.forename: Kanehiro
authors.initials: K
authors.lastname: Fujiyoshi
authors.affiliation: Division of Regenerative Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan.
authors.forename: Hirotaka J
authors.initials: HJ
authors.lastname: Okano
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.|Laboratory for Marmoset Neural Architecture, Brain Science Institute RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D004195:Disease Models, Animal; D059907:Functional Neuroimaging / Q000379:methods*; D006930:Hyperalgesia / Q000175:diagnosis*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000502:physiology*; D010146:Pain; D010812:Physical Stimulation; D011984:Sensory Receptor Cells / Q000502:physiology*; D013127:Spinal Nerves / Q000601:surgery; D014110:Touch