title: Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury.
abstract: BACKGROUND
  Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator derived from cell membrane. It has been reported that PAF is involved in various pathological conditions, such as spinal cord injury, multiple sclerosis, neuropathic pain and intrathecal administration of PAF leads to tactile allodynia. However, the expression of PAF synthases and its receptor in the spinal cord following peripheral nerve injury is unknown.
  
  
  METHODS
  Using the rat spared nerve injury (SNI) model, we investigated the expression of PAF synthases (LPCAT1 and 2) and PAF receptor (PAFr) mRNAs in the spinal cord. Reverse transcription polymerase chain reaction (RT-PCR) and double-labeling analysis of in situ hybridization histochemistry (ISHH) with immunohistochemistry (IHC) were employed for the analyses. Pain behaviors were also examined with PAFr antagonist (WEB2086).
  
  
  RESULTS
  RT-PCR showed that LPCAT2 mRNA was increased in the ipsilateral spinal cord after injury, but not LPCAT1 mRNA. Double-labeling of ISHH with IHC revealed that LPCAT1 and 2 mRNAs were constitutively expressed by a subset of neurons, and LPCAT2 mRNA was increased in spinal microglia after nerve injury. RT-PCR showed that PAFr mRNA was dramatically increased in the ipsilateral spinal cord after nerve injury. Double-labeling analysis of ISHH with IHC revealed that after injury PAFr mRNA was predominantly colocalized with microglia in the spinal cord. Continuous intrathecal administration of the PAFr antagonist suppressed mechanical allodynia following peripheral nerve injury. Delayed administration of a PAFr antagonist did not reverse the mechanical allodynia.
  
  
  CONCLUSIONS
  Our data show the histological localization of PAF synthases and its receptor in the spinal cord following peripheral nerve injury, and suggest that PAF/PAFr signaling in the spinal cord acts in an autocrine or paracrine manner among the activated microglia and neurons, thus contributing to development of neuropathic pain.
authors.affiliation: Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Okubo
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Kimiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hirosato
authors.initials: H
authors.lastname: Kanda
authors.forename: Yi
authors.initials: Y
authors.lastname: Dai
authors.forename: Koichi
authors.initials: K
authors.lastname: Noguchi
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology / Q000627:therapeutic use; D004789:Enzyme Activation / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007278:Injections, Spinal; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009437:Neuralgia / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D059348:Peripheral Nerve Injuries / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001381:Azepines; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D048051:p38 Mitogen-Activated Protein Kinases