title: Coupled Activation of Primary Sensory Neurons Contributes to Chronic Pain.
abstract: Primary sensory neurons in the DRG play an essential role in initiating pain by detecting painful stimuli in the periphery. Tissue injury can sensitize DRG neurons, causing heightened pain sensitivity, often leading to chronic pain. Despite the functional importance, how DRG neurons function at a population level is unclear due to the lack of suitable tools. Here we developed an imaging technique that allowed us to simultaneously monitor the activities of >1,600 neurons/DRG in live mice and discovered a striking neuronal coupling phenomenon that adjacent neurons tend to activate together following tissue injury. This coupled activation occurs among various neurons and is mediated by an injury-induced upregulation of gap junctions in glial cells surrounding DRG neurons. Blocking gap junctions attenuated neuronal coupling and mechanical hyperalgesia. Therefore, neuronal coupling represents a new form of neuronal plasticity in the DRG and contributes to pain hypersensitivity by "hijacking" neighboring neurons through gap junctions.
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA; Department of Neuroscience & Cell Biology, the University of Texas Medical Branch School of Medicine, 301 University Boulevard, Galveston, TX 77555, USA. Electronic address: yukim@utmb.edu.
authors: Yu Shin
authors: YS
authors: Kim
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Michael
authors: M
authors: Anderson
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Kyoungsook
authors: K
authors: Park
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Qin
authors: Q
authors: Zheng
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Amit
authors: A
authors: Agarwal
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Catherine
authors: C
authors: Gong
authors: Department of Orthopaedic Surgery, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA; Department of Orthopaedics, the First Affiliated Hospital, Orthopaedic Institute, Soochow University, People's Republic of China.
authors: Saijilafu
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: LeAnne
authors: L
authors: Young
authors: Department of Anesthesiology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Shaoqiu
authors: S
authors: He
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Pamela Colleen
authors: PC
authors: LaVinka
authors: Department of Orthopaedic Surgery, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Fengquan
authors: F
authors: Zhou
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Dwight
authors: D
authors: Bergles
authors: Hadassah-Hebrew University Medical Center, Mt. Scopus, Jerusalem 91240, Israel.
authors: Menachem
authors: M
authors: Hanani
authors: Department of Anesthesiology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors: Yun
authors: Y
authors: Guan
authors: The Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors: David C
authors: DC
authors: Spray
authors: Departments of Neuroscience, Neurosurgery, and Dermatology, Center of Sensory Biology, the Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: xdong2@jhmi.edu.
authors: Xinzhong
authors: X
authors: Dong
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000293:injuries / Q000502:physiology*; D017629:Gap Junctions / Q000502:physiology; D006930:Hyperalgesia / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D015854:Up-Regulation