Activation of extracellular signal-regulated protein kinases 5 in primary afferent neurons contributes to heat and cold hyperalgesia after inflammation.
Heat and cold hyperalgesia is a common feature of inflammatory pain. To investigate whether activation of extracellular signal-regulated protein kinase 5 (ERK5), also known as big mitogen-activated protein kinase 1, in primary sensory neurons participates in inflammatory pain, we examined the phosphorylation of ERK5 in the dorsal root ganglion (DRG) after peripheral inflammation. Inflammation induced by complete Freund's adjuvant produced heat and cold hyperalgesia on the ipsilateral hind paw and induced an increase in the phosphorylation of ERK5, mainly in tyrosine kinase A-expressing small- and medium-size neurons. In contrast, there was no change in ERK5 phosphorylation in the spinal dorsal horn. ERK5 antisense, but not mismatch, oligodeoxynucleotide decreased the activation of ERK5 and suppressed inflammation-induced heat and cold hyperalgesia. Furthermore, the inhibition of ERK5 blocked the induction of transient receptor potential channel TRPV1 and TRPA1 expression in DRG neurons after peripheral inflammation. Our results show that ERK5 activated in DRG neurons contribute to the development of inflammatory pain. Thus, blocking ERK5 signaling in sensory neurons that has the potential for preventing pain after inflammation.
Katsura
Hirokazu
H
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Obata
Koichi
K
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Mizushima
Toshiyuki
T
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Sakurai
Jun
J
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Kobayashi
Kimiko
K
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Yamanaka
Hiroki
H
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Dai
Yi
Y
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Fukuoka
Tetsuo
T
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Sakagami
Masafumi
M
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
Noguchi
Koichi
K
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, JapanDepartment of Otorhinolaryngology, Hyogo College of Medicine, Mukogawa-cho, Nishinomiya, Hyogo, Japan.
D000818:Animals; D001522:Behavior, Animal; D004789:Enzyme Activation / Q000502:physiology; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000473:pathology*; D006930:Hyperalgesia / Q000473:pathology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications; D008297:Male; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000201:enzymology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D013997:Time Factors
D016900:Neurofilament Proteins; D016376:Oligonucleotides, Antisense; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C051774:neurofilament protein H; D005620:Freund's Adjuvant; D020917:Receptor, trkA; D048054:Mitogen-Activated Protein Kinase 7