Activation of extracellular signal-regulated protein kinase in dorsal horn neurons in the rat neuropathic intermittent claudication model.
Extracellular signal-regulated protein kinase (ERK) is a mitogen-activated protein kinase (MAPK) that mediates several cellular responses to mitogenic and differentiation signals, and activation of ERK in dorsal horn neurons by noxious stimulation is known to contribute to pain hypersensitivity. In order to elucidate the pathophysiological mechanisms of the cauda equina syndrome, secondary to spinal canal stenosis, we evaluated walking dysfunction triggered by forced exercise and activation of ERK in the dorsal horn using a rat model of neuropathic intermittent claudication. Rats in the lumbar canal stenosis (LCS) group showed a shorter running distance from 1 to 14 days after surgery. Two minutes after running on the treadmill apparatus, phosphorylation of ERK was induced in neurons in the superficial laminae in the LCS group but not in the sham group, whereas there was no change in the deeper laminae. Intrathecal administration of the MAPK kinase inhibitor, U0126, 30 min before running, clearly increased the running distance, whereas there was no significant change in the vehicle control group 3 days after surgery. In addition, a prostaglandin E1 analog, OP-1206 alpha-CD, administered orally, improved the walking dysfunction, and further, inhibited activation of ERK following running 7 days after surgery. These findings suggest that intermittent claudication triggered by forced walking might affect the phosphorylation of ERK in the superficial laminae, possibly via transient (partial) ischemia of the spinal cord. ERK activation in the dorsal horn neurons may be involved in the transient pain in the neuropathic intermittent claudication model.
Liu
Yi
Y
Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Obata
Koichi
K
Yamanaka
Hiroki
H
Dai
Yi
Y
Fukuoka
Tetsuo
T
Tokunaga
Atsushi
A
Noguchi
Koichi
K
D000527:Alprostadil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000704:Analysis of Variance; D000818:Animals; D002070:Butadienes / Q000008:administration & dosage; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D007150:Immunohistochemistry / Q000379:methods; D007383:Intermittent Claudication / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009570:Nitriles / Q000008:administration & dosage; D020671:Posterior Horn Cells / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013130:Spinal Stenosis / Q000503:physiopathology; D016138:Walking / Q000502:physiology
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; C025090:ONO 1206; D020928:Mitogen-Activated Protein Kinases; D000527:Alprostadil