title: Roles of extracellular signal-regulated protein kinases 5 in spinal microglia and primary sensory neurons for neuropathic pain.
abstract: Neuropathic pain that occurs after peripheral nerve injury is poorly controlled by current therapies. Increasing evidence shows that mitogen-activated protein kinase (MAPK) play an important role in the induction and maintenance of neuropathic pain. Here we show that activation of extracellular signal-regulated protein kinases 5 (ERK5), also known as big MAPK1, participates in pain hypersensitivity caused by nerve injury. Nerve injury increased ERK5 phosphorylation in spinal microglia and in both damaged and undamaged dorsal root ganglion (DRG) neurons. Antisense knockdown of ERK5 suppressed nerve injury-induced neuropathic pain and decreased microglial activation. Furthermore, inhibition of ERK5 blocked the induction of transient receptor potential channels and brain-derived neurotrophic factor expression in DRG neurons. Our results show that ERK5 activated in spinal microglia and DRG neurons contributes to the development of neuropathic pain. Thus, blocking ERK5 signaling in the spinal cord and primary afferents has potential for preventing pain after nerve damage.
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Obata
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Katsura
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sakurai
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fukuoka
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000473:pathology*; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D017628:Microglia / Q000201:enzymology*; D048054:Mitogen-Activated Protein Kinase 7 / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000209:etiology / Q000473:pathology*; D009475:Neurons, Afferent / Q000201:enzymology*; D009570:Nitriles / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000473:pathology; D050916:TRPV Cation Channels / Q000378:metabolism; D013997:Time Factors
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D009570:Nitriles; D016376:Oligonucleotides, Antisense; D050916:TRPV Cation Channels; C113580:U 0126; D048054:Mitogen-Activated Protein Kinase 7