Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Spinal N-acetyl-alpha-linked acidic dipeptidase (NAALADase) inhibition attenuates mechanical allodynia induced by paw carrageenan injection in the rat. 1147 30

Increased glutamate availability in the spinal cord and primary afferent nerves plays an important role in acute and chronic pain. Afferent ectopic discharges from the site of nerve injury constitute a source of abnormal sensory input to the spinal dorsal horn. The ectopic afferent activity is largely responsible for the development of hypersensitivity of dorsal horn neurons and neuropathic pain. Inhibition of glutamate carboxypeptidase II (GCP II) reduces glutamate release generated from N-acetyl-aspartyl-glutamate in nerve tissues and may have an analgesic effect on neuropathic pain. In the present study, we determined the effect of a GCP II inhibitor, 2-(phosphono-methyl)-pentanedioic acid (2-PMPA), on allodynia and ectopic afferent discharges in an animal model of neuropathic pain. Neuropathic pain was induced by partial ligation of the left sciatic nerve in rats. Tactile allodynia was assessed using von Frey filaments applied to the plantar surface of the injured hindpaw. Single-unit activity of ectopic discharges was recorded from the sciatic nerve proximal to the site of ligation. Intravenous injection of 50 to 100 mg/kg 2-PMPA significantly reduced allodynia in a dose-dependent manner. Furthermore, 2-PMPA dose-dependently attenuated the ectopic discharge activity of injured sciatic afferent nerves. At a dose of 100 mg/kg, 2-PMPA significantly inhibited the ectopic activity from 14.7 +/- 2.1 to 4.4 +/- 0.5 impulses/s without altering the conduction velocity of afferent nerves. Therefore, these data suggest that the antiallodynic effect of 2-PMPA may be mediated, at least in part, by inhibition of ectopic afferent discharges at the site of nerve injury.
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PMID:Effect of 2-(phosphono-methyl)-pentanedioic acid on allodynia and afferent ectopic discharges in a rat model of neuropathic pain. 1180 30