Inhibition of spinal N-acetylated-α-linked acidic dipeptidase produces an antinociceptive effect in the rat formalin test

Yamamoto, Tatsuo; Nozaki-Taguchi, Natsuko; Sakashita, Yoshihiko; Inagaki, Taisuke

doi:10.1016/s0306-4522(00)00502-9

Cited by 46 publications

(62 citation statements)

References 26 publications

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“…In the light of these findings, the inhibitory effect of 2-PMPA on morphine tolerance may be explained by its effects at NMDA, mGluRII, or both receptors. Moreover, the results of Experiment 2 indicate that 2-PMPA, at the dose effectively inhibiting development of morphine tolerance, produced no antinociceptive effect in the tail-flick test, which is in agreement with a recent report of Yamamoto et al that showed lack of an antinociceptive effect of 2-PMPA in another acute pain (hot plate) test (Yamamoto et al, 2001b).…”

Section: Effects Of Gcp II Inhibition On Morphine Tolerancesupporting

confidence: 91%

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Popik

Kozela

Wróbel

et al. 2002

Neuropsychopharmacol

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Inhibition of glutamate carboxypeptidase II (GCP II; NAALADase) produces a variety of effects on glutamatergic neurotransmission. The aim of this study was to investigate effects of GCP II inhibition with the selective inhibitor, 2-PMPA, on: (a) development of tolerance to the antinociceptive effects, (b) withdrawal, and (c) conditioned reward produced by morphine in C57/Bl mice. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily (b.i.d.) administration of 2-PMPA and 10 mg/kg of morphine. Opioid withdrawal was measured 3 days after twice daily morphine (30 or 10 mg/kg) administration, followed by naloxone challenge. Conditioned morphine reward was investigated using conditioned place preference with a single morphine dose (10 mg/kg). High doses of 2-PMPA inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg of the NMDA receptor antagonist, memantine) while not affecting the severity of withdrawal. A high dose of 2-PMPA (100 mg/kg) also significantly potentiated morphine withdrawal, but inhibited both acquisition and expression of morphine-induced conditioned place preference. Memantine inhibited the intensity of morphine withdrawal as well as acquisition and expression of morphine-induced conditioned place preference. In addition, 2-PMPA did not affect learning or memory retrieval in a simple two-trial test, nor did it produce withdrawal symptoms in morphinedependent, placebo-challenged mice. Results suggest involvement of GCP II (NAALADase) in phenomena related to opioid addiction.

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Section: Effects Of Gcp II Inhibition On Morphine Tolerancesupporting

confidence: 91%

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Popik

Kozela

Wróbel

et al. 2002

Neuropsychopharmacol

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“…12 Intrathecal administration of NAAG peptidase inhibitors produces an analgesic effect in both inflammatory pain models and in neuropathic pain models. [13][14][15][16] Taken together, these data support the hypothesis that α-2 adrenergic receptor agonists, NMDA receptor antagonists, and NAAG peptidase inhibitors may have some analgesic effects on bone cancer pain. At present, however, the efficacy of these drugs on bone cancer pain has not been examined comprehensively.…”

Section: Conclusion : Les Agonistes α-2 Produisent Un Effet Analgésiqsupporting

confidence: 75%

“…We previously reported that intrathecal administration of 2-(phosphonomethyl)pentanedioic acid, a NAAG peptidase inhibitor, produces an analgesic effect in the rat formalin test and carrageenan test, with a bell-shaped dose-response curve. 13,14 We do not know the mechanisms underlying the dose-response curves for these two structurally different NAAG peptidase inhibitors in these pain models. It has been reported that a high concentration of NAAG acts as a NMDA receptor agonist.…”

Section: Discussionmentioning

confidence: 99%

Regional Anesthesia and Pain

Saito

Aoe

Kozikowski

et al. 2006

Can J Anesth/J Can Anesth

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Purpose: Not all bone cancer pain can be effectively treated with current therapies. In the present study, the effects of ip administration of α-2 agonists (dexmedetomidine and clonidine), N-methyl-D-aspartate (NMDA) antagonists (MK-801 and ketamine), an N-acetylaspartylglutamate peptidase inhibitor (ZJ-43), and morphine were examined in a mouse bone cancer pain model. Methods:A bone cancer pain model was produced by injection of murine sarcoma cells into the medullary cavity of the distal femur. To estimate the level of bone cancer pain, the number of pain-related behaviours induced by repeated applications of a von Frey monofilament (0.166 g) to the site of tumour cells implantation was counted. Drugs were administered two weeks after the implantation.Results: Morphine produced a significant analgesic effect (P < 0.001). The α-2 agonists produced analgesic effects (P < 0.001) with an efficacy similar to that of morphine, but only at doses that produced severe sedation. MK-801 had only limited analgesic effects, while ketamine produced an analgesic effect (P < 0.001) with the same efficacy as morphine. ZJ-43 (100 mg·kg -1 ) had a significant analgesic effect (P < 0.05) and the effect of ZJ-43 was antagonized by the selective group II metabotropic glutamate receptor (mGluR) antagonist. Conclusion:These data suggest that α-2 agonists produce an analgesic effect only at a sedative dose and that ketamine, but not MK-801, is associated with an analgesic response without overt side effects. The effect of ZJ-43 is mediated by activating group II mGluRs. Objectif : Les douleurs du cancer des os ne sont pas toujours soulagées par les traitements habituels. Dans la présente étude, les effets de l'administration ip d'agonistes α-2 (dexmédétomi-dine et clonidine), d'antagonistes N-méthyl-D-aspartate (NMDA) (MK-801 et kétamine), d'un inhibiteur de N-acétylaspartylgluta-mate peptidase (ZJ-43) et de morphine ont été examinés dans un modèle de douleur du cancer des os chez la souris. Méthode : Un modèle de douleur du cancer des os a été produit en injectant des cellules de sarcome d'Ewing dans la cavité médul-laire distale du fémur. Pour évaluer le niveau de douleur, nous avons calculé le nombre de mouvements reliés à la douleur induite par l'application répétée d'un monofilament von Frey (0,166 g) au site de la tumeur implantée. Les médicaments ont été administrés deux semaines après l'implantation.Résultats : La morphine a produit une analgésie significative (P < 0,001). Les agonistes α-2 ont produit une analgésie (P < 0,001) similaire à celle de la morphine, mais seulement à des doses produisant une sédation importante. Le MK-801 a eu un effet limité et la kétamine a produit une analgésie aussi efficace que celle de la morphine (P < 0,001). ) a eu un effet analgésique significatif (P < 0,05)

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“…Intrathecal injection of 2-PMPA also depresses both the phase 1 and phase 2 flinching behaviors in rats caused by formalin injection (Yamamoto et al, 2001b). In the present study, systemic injection of 2-PMPA significantly attenuated allodynia induced by sciatic nerve injury in rats.…”

Section: Gcp II Inhibitor and Neuropathic Pain 665supporting

confidence: 68%

Effect of 2-(Phosphono-methyl)-pentanedioic Acid on Allodynia and Afferent Ectopic Discharges in a Rat Model of Neuropathic Pain

Chen¹,

Wozniak²,

Slusher³

et al. 2002

J Pharmacol Exp Ther

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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-acetylaspartyl-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

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Inhibition of spinal N-acetylated-α-linked acidic dipeptidase produces an antinociceptive effect in the rat formalin test

Cited by 46 publications

References 26 publications

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Regional Anesthesia and Pain

Effect of 2-(Phosphono-methyl)-pentanedioic Acid on Allodynia and Afferent Ectopic Discharges in a Rat Model of Neuropathic Pain

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