title: Intracisternal administration of NR2 subunit antagonists attenuates the nociceptive behavior and p-p38 MAPK expression produced by compression of the trigeminal nerve root.
abstract: BACKGROUND
  We investigated the role of the central NMDA receptor NR2 subunits in the modulation of nociceptive behavior and p-p38 MAPK expression in a rat model with compression of the trigeminal nerve root. To address this possibility, changes in air-puff thresholds and pin-prick scores were determined following an intracisternal administration of NR2 subunit antagonists. We also examined effects of NR2 subunit antagonists on the p-p38 MAPK expression.
  
  
  RESULTS
  Experiments were carried out using male Sprague-Dawley rats weighing (200-230 g). Compression of the trigeminal nerve root was performed under pentobarbital sodium (40 mg/kg) anesthesia. Compression of the trigeminal nerve root produced distinct nociceptive behavior such as mechanical allodynia and hyperalgesia. Intracisternal administration of 10 or 20 μg of D-AP5 significantly increased the air-puff threshold and decreased the pin-prick scores in a dose-dependent manner. The intracisternal administration of PPPA (1, 10 μg), or PPDA (5, 10 μg) increased the air-puff threshold and decreased the pin-prick scores ipsilateral as well as contralateral to the compression of the trigeminal root. Compression of the trigeminal nerve root upregulated the expression of p-p38 MAPK in the ipsilateral medullary dorsal horn which was diminished by D-AP5, PPPA, PPDA, but not Ro25-6981.
  
  
  CONCLUSIONS
  Our findings suggest that central NMDA receptor NR2 subunits play an important role in the central processing of trigeminal neuralgia-like nociception in rats with compression of the trigeminal nerve root. Our data further indicate that the targeted blockade of NR2 subunits is a potentially important new treatments strategy for trigeminal neuralgia-like nociception.
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea. dkahn@knu.ac.kr.
authors.forename: Hye J
authors.initials: HJ
authors.lastname: Jeon
authors.forename: Seung R
authors.initials: SR
authors.lastname: Han
authors.forename: Koang H
authors.initials: KH
authors.lastname: Lim
authors.forename: Kyoung A
authors.initials: KA
authors.lastname: Won
authors.forename: Yong C
authors.initials: YC
authors.lastname: Bae
authors.forename: Dong K
authors.initials: DK
authors.lastname: Ahn
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003979:Diazonium Compounds / Q000008:administration & dosage / Q000494:pharmacology; D004333:Drug Administration Routes; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D011843:Radiculopathy / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D014276:Trigeminal Nerve / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D003979:Diazonium Compounds; D010636:Phenols; D010880:Piperidines; D011725:Pyridines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; C056729:4-(2'-pyridyldithio)benzyldiazoacetate; D048051:p38 Mitogen-Activated Protein Kinases