Spinal N-acetyl-alpha-linked acidic dipeptidase (NAALADase) inhibition attenuates mechanical allodynia induced by paw carrageenan injection in the rat.
N-Acetylated-alpha-linked acidic dipeptidase (NAALADase) hydrolyzes N-acetyl-aspartyl-glutamate (NAAG) to liberate N-acetyl-aspartate and glutamate. NAAG is a putative neurotransmitter and acts as a mixed agonist/antagonist on N-methyl-D-aspartate (NMDA) receptors and acts as an agonist on the metabotropic glutamate receptor 3 (mGluR3). In the present study, we examined the role of spinal NAALADase in the maintenance of mechanical allodynia induced by carrageenan injection, skin incision and mild thermal injury using 2-(phosphonomethyl)pentanedioic acid (2-PMPA), a specific NAALADase inhibitor, in rats. Mechanical allodynia was induced by injection of 2 mg carrageenan into the paw (carrageenan model), by creating a 1-cm longitudinal skin incision of the plantar aspect of the foot (post-operative model), or by application of thermal stimulation (52.5 degrees C) for 45 s to the hind paw (mild thermal injury model). 2-PMPA was administered intrathecally at the time when the maximum mechanical allodynia occurred. Mechanical allodynia was assessed by the measurement of mechanical threshold using von Frey filaments. The mechanical threshold was measured 5, 15, 30, 60 and 90 min after the drug administration. In the carrageenan model, 100 microg of 2-PMPA attenuated the level of mechanical allodynia. 2-PMPA had no effect on the level of mechanical allodynia in both the post-operative pain model and the mild thermal injury model. These data suggested that the inhibition of spinal NAALADase alleviated mechanical allodynia induced by paw carrageenan injection.
Yamamoto
T
T
Department of Anesthesiology, School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, 260-0856, Chiba, Japan. yamatat@med.m.chiba-u.ac.jp
Nozaki-Taguchi
N
N
Sakashita
Y
Y
D000818:Animals; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002351:Carrageenan / Q000494:pharmacology; D004151:Dipeptides / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D043425:Glutamate Carboxypeptidase II; D006614:Hindlimb / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects* / Q000201:enzymology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D017288:Pain Threshold / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology
C402107:2-(phosphonomethyl)pentanedioic acid; D004151:Dipeptides; D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; C027172:isospaglumic acid; D002351:Carrageenan; D002268:Carboxypeptidases; D043425:Glutamate Carboxypeptidase II