Phosphorylation of ezrin/radixin/moesin (ERM) protein in spinal microglia following peripheral nerve injury and lysophosphatidic acid administration.
Peripheral nerve injury activates spinal glial cells, which may contribute to the development of pain behavioral hypersensitivity. There is growing evidence that activated microglia show dynamic changes in cell morphology; however, the molecular mechanisms that underlie the modification of the membrane and cytoskeleton of microglia are not known. Here, we investigated the phosphorylation of ezrin, radixin, and moesin (ERM) proteins in the spinal cord after peripheral nerve injury. ERM is known to function as membrane-cytoskeletal linkers and be localized at filopodia- and microvilli-like structures. ERM proteins must be phosphorylated at a specific C-terminal threonine residue to be in the active state. The nature of ERM proteins in the spinal cord of animals in a neuropathic pain model has not been investigated and characterized. In the present study, we observed an increase in the phosphorylated ERM in the spinal microglia following spared nerve injury. The intrathecal administration of lysophosphatidic acid induced the phosphorylation of ERM proteins in microglia along with the development of mechanical pain hypersensitivity. Intrathecal administration of ERM antisense locked nucleic acid suppressed nerve injury-induced tactile allodynia and decreased the phosphorylation of ERM, but not the Iba1 staining pattern, in spinal glial cells. These findings suggest that lysophosphatidic acid induced the phosphorylation of ERM proteins in spinal microglia and may be involved in the emergence of neuropathic pain. These findings may underlie the pathological mechanisms of nerve injury-induced neuropathic pain.
Department of Ophthalmology, Hyogo College of Medicine, Nishinomiya, Japan.
Ryosuke
R
Kashimoto
Hiroki
H
Yamanaka
Kimiko
K
Kobayashi
Masamichi
M
Okubo
Hideshi
H
Yagi
Osamu
O
Mimura
Koichi
K
Noguchi
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D008246:Lysophospholipids; D008565:Membrane Proteins; D008840:Microfilament Proteins; D000099149:Ezrin; C071058:moesin; C071776:radixin; C032881:lysophosphatidic acid