Premium
Roles of extracellular signal‐regulated protein kinases 5 in spinal microglia and primary sensory neurons for neuropathic pain
Author(s) -
Obata Koichi,
Katsura Hirokazu,
Mizushima Toshiyuki,
Sakurai Jun,
Kobayashi Kimiko,
Yamanaka Hiroki,
Dai Yi,
Fukuoka Tetsuo,
Noguchi Koichi
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04656.x
Subject(s) - neuropathic pain , nerve injury , microglia , peripheral nerve injury , dorsal root ganglion , neuroscience , neurotrophic factors , medicine , mapk/erk pathway , spinal cord , brain derived neurotrophic factor , kinase , anesthesia , microbiology and biotechnology , receptor , biology , sciatic nerve , inflammation
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.