Spinal d-Amino Acid Oxidase Contributes to Neuropathic Pain in Rats

Zhao, Wenjuan; Gao, Zhenyu; Wang, Hong; Nie, Hui; Zhao, Qian; Zhou, Xiangjun; Wang, Yongxiang

doi:10.1124/jpet.109.158816

Cited by 48 publications

(43 citation statements)

References 36 publications

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“…Systemic and intrathecal administration of the DAO inhibitor sodium benzoate also specifically attenuated L5/L6 spinal nerve tight ligation-induced neuropathic mechanical allodynia and formalin-induced tonic pain in rats and mice. In contrast, sodium benzoate administered by either route was not effective in acute pain such as the early-phase flinch response in the formalin test or thermal nociceptive response in the tail-flick test or hot-plate test (Zhao et al, 2008(Zhao et al, , 2010. Moreover, L5/L6 spinal nerve damage up-regulated spinal DAO gene expression and DAO enzymatic activity, with the same time course as peripheral nerve damage-induced mechanical allodynia (Zhao et al, 2010).…”

Section: Introductionmentioning

confidence: 92%

“…Moreover, L5/L6 spinal nerve damage up-regulated spinal DAO gene expression and DAO enzymatic activity, with the same time course as peripheral nerve damage-induced mechanical allodynia (Zhao et al, 2010). Thus, we have obtained the first evidence indicating that spinal DAO specifically participates in chronic pain transmission and is a potential target molecule for the treatment of chronic pain including chronic neuropathic pain (Zhao et al, 2008(Zhao et al, , 2010. However, several issues need to be clarified before validation of the hypothesis of spinal DAO as an efficacious pain target molecule.…”

Section: Introductionmentioning

confidence: 97%

“…3B). For a comparison, 1.5 (2 nmol) and 10 g (13.2 nmol) of morphine sulfate administered intrathecally abolished formalin-induced tonic pain by 50 and 100%, respectively (Wang et al, 2000;Zhao et al, 2010). Because the tonic phase flinches were measured subsequently after the acute phase, the differential effects of CBIO on the acute and tonic phases may be caused by its variable tissue concentrations/pharmacokinetics changes at different time points.…”

Section: Spinal Dao Inhibitors On Pain 285mentioning

confidence: 99%

“…In addition, sodium benzoate (benzoic acid) is the only DAO inhibitor used so far in animal pain studies and without dose-response analysis. Because of its low potency and rapid excretion in urine (Kubota and Ishizaki, 1991;MacArthur et al, 2004;Williams and Lock, 2005;Xin et al, 2007), it was widely accepted to give sodium benzoate in high doses such as 100 to 1000 mg/kg for systemic administration (Moses et al, 1996;Williams and Lock, 2005;Xin et al, 2005Xin et al, , 2007Wu et al, 2006;Zhao et al, 2008Zhao et al, , 2010. It is reasonable to speculate that the analgesic action of sodium benzoate may be a result of its possible nonspecific effects caused by high doses.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, sodium benzoate administered by either route was not effective in acute pain such as the early-phase flinch response in the formalin test or thermal nociceptive response in the tail-flick test or hot-plate test (Zhao et al, 2008(Zhao et al, , 2010. Moreover, L5/L6 spinal nerve damage up-regulated spinal DAO gene expression and DAO enzymatic activity, with the same time course as peripheral nerve damage-induced mechanical allodynia (Zhao et al, 2010). Thus, we have obtained the first evidence indicating that spinal DAO specifically participates in chronic pain transmission and is a potential target molecule for the treatment of chronic pain including chronic neuropathic pain (Zhao et al, 2008(Zhao et al, , 2010.…”

Section: Introductionmentioning

confidence: 99%

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A Series of d-Amino Acid Oxidase Inhibitors Specifically Prevents and Reverses Formalin-Induced Tonic Pain in Rats

Gong

Gao²,

Wang³

et al. 2010

J Pharmacol Exp Ther

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We have found that mutation of D-amino acid oxidase (DAO) diminished formalin-induced tonic pain. The present research further studied the analgesic effects of a series of DAO inhibitors in this model. 5-Chlorobenzo[d]isoxazol-3-ol (CBIO), 4H-thieno[3,2-b]pyrrole-5-carboxylic acid (compound 8), 5-methylpyrazole-3-carboxylic acid (AS057278), sodium benzoate, and 4-nitro-3-pyrazole carboxylic acid (NPCA) inhibited rat spinal cord-derived DAO activity in a concentration-dependent manner, with maximal inhibition of 100% and potency rank of CBIO Ͼ compound 8 Ͼ AS057278 Ͼ sodium benzoate Ͼ NPCA. In rats, intrathecal injections of CBIO, compound 8, AS057278, and sodium benzoate but not NPCA specifically prevented formalin-induced tonic pain but not acute nociception, with the same potency order as in the DAO activity assay. The highly potent analgesia of DAO inhibitors was evidenced by CBIO, which prevented 50% pain at 0.06 g, approximately 5-fold the potency of morphine. CBIO given after formalin challenge also reversed the established pain state to the same degree as prevention. The antihyperalgesic potencies of these DAO inhibitors were highly correlated to their inhibitions of spinal DAO activity. Maximum inhibition of pain by these compounds was approximately 60%, comparable with that of the N-methyl-D-aspartic acid receptor antagonist (ϩ)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), suggesting that a larger portion of formalin-induced tonic pain is "DAO-sensitive," whereas the remaining 40% of tonic pain and acute nociception is "DAO-insensitive." These findings, combined with our previous DAO gene mutation and induction results, indicate spinal DAO mediates both induction and maintenance of formalin-induced tonic pain and further validate spinal DAO as a novel and efficacious target molecule for the treatment of chronic pain.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 97%

Section: Spinal Dao Inhibitors On Pain 285mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A Series of d-Amino Acid Oxidase Inhibitors Specifically Prevents and Reverses Formalin-Induced Tonic Pain in Rats

Gong

Gao²,

Wang³

et al. 2010

J Pharmacol Exp Ther

Self Cite

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d-Amino acids in the brain and mutant rodents lacking d-amino-acid oxidase activity

et al. 2012

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D-Amino acids are stereoisomers of L-amino acids. They are often called unnatural amino acids, but several D-amino acids have been found in mammalian brains. Among them, D-serine is abundant in the forebrain and functions as a co-agonist of NMDA receptors to enhance neurotransmission. D-Amino-acid oxidase (DAO), which degrades neutral and basic D-amino acids, is mainly present in the hindbrain. DAO catabolizes D-serine and, therefore, modulates neurotransmission. In the brains of mutant mice and rats lacking DAO activity, the amounts of D-serine and other D-amino acids are markedly increased. Mutant mice manifested behavioral changes characteristic of altered NMDA receptor activity, likely due to increased levels of D-serine. D-Serine and DAO have been demonstrated to play important roles in cerebellar development and synaptic plasticity. They have also implicated in amyotrophic lateral sclerosis and pain response. There have also been several lines of evidence correlating DAO with schizophrenia. Taken together, the experiments indicate that D-amino acids and DAO have pivotal functions in the central nervous system.

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Contributions of spinal d-amino acid oxidase to bone cancer pain

et al. 2012

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D-Amino acid oxidase (DAAO), a FAD-dependent peroxisomal flavoenzyme that catalyzes oxidation of D-amino acids to hydrogen peroxide, is distributed in the spinal cord almost exclusively expressed within astrocytes. The present study aims to explore potential contributions of spinal DAAO to the development of bone cancer pain and morphine tolerance to analgesia. Tibia inoculation of carcinoma cells produced mechanical allodynia (but not heat hyperalgesia), in synchronous with induction of DAAO expression and DAAO enzymatic activity, as well as activation of spinal astrocytes marked by GFAP. Subcutaneous and intrathecal injection of the specific DAAO inhibitor CBIO (5-chloro-benzo[d]isoxazol-3-ol) blocked mechanical allodynia in a dose- and time-dependent manner in tumor-bearing rats, with maximum inhibition of 40-50 %. Multi-daily intrathecal injections of the DAAO gene silencer siRNA/DAAO also yielded anti-allodynic effects by approximately 40 % and the analgesia remained for at least 6 days. Subcutaneous injection of CBIO suppressed the production of spinal hydrogen peroxide and GFAP expression. 7-Day multiple bi-daily injections of CBIO produced anti-allodynia without inducing self-tolerance to analgesia or cross-tolerance to morphine, and concurrent injections of CBIO with morphine produced apparent additive anti-allodynia and completely prevented morphine tolerance in behaviors and spinal expression of μ-opioid receptors. Our results provide the first evidence that spinal DAAO contributes to the development of morphine tolerance to analgesia and bone cancer pain accounting for 40-50 % pain status, probably via production of hydrogen peroxide leading to activation of astrocytes. The unique characterizations of DAAO inhibitors make them a potential for the treatment of cancer pain when they are administered alone or in combination with morphine.

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Spinal d-Amino Acid Oxidase Contributes to Neuropathic Pain in Rats

Cited by 48 publications

References 36 publications

A Series of d-Amino Acid Oxidase Inhibitors Specifically Prevents and Reverses Formalin-Induced Tonic Pain in Rats

A Series of d-Amino Acid Oxidase Inhibitors Specifically Prevents and Reverses Formalin-Induced Tonic Pain in Rats

d-Amino acids in the brain and mutant rodents lacking d-amino-acid oxidase activity

Contributions of spinal d-amino acid oxidase to bone cancer pain

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