ArticleBritish journal of pharmacology2012
D-Amino acid oxidase-mediated increase in spinal hydrogen peroxide is mainly responsible for formalin-induced tonic pain.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 58 citations in OpenAlex.
- Site-specific drug release of monomethyl fumarate to treat oxidative stress disorders.Nature biotechnology · 2025Article
- DAAO Mutant Sites among Different Mice Strains and Their Effects on Enzyme Activity.The protein journal · 2025Article
- d-Serine Inhibits Non-ionotropic NMDA Receptor Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.Current neuropharmacology · 2024Review
- Identifying Genomic Signatures of Positive Selection to Predict Protective Genomic Loci in the Cohort of Lithuanian Clean-Up Workers of the Chornobyl Nuclear Disaster.Current issues in molecular biology · 2023Article
- Article
- Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects.Cell research · 2022Article
- Mouse strain specificity of DAAO inhibitors-mediated antinociception.Pharmacology research & perspectives · 2021Article
- Ulinastatin Exhibits Antinociception in Rat Models of Acute Somatic and Visceral Pain Through Inhibiting the Local and Central Inflammation.Journal of pain research · 2021Article
- Precision Medicine of Sodium Benzoate for the Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD).Neuropsychiatric disease and treatment · 2020Article
- Involvement of d-amino acid oxidase in cerebral ischaemia induced by transient occlusion of the middle cerebral artery in mice.British journal of pharmacology · 2019Article
- The Role of N-Methyl-D-Aspartate Receptor Neurotransmission and Precision Medicine in Behavioral and Psychological Symptoms of Dementia.Frontiers in pharmacology · 2019Review
- An integrated review on new targets in the treatment of neuropathic pain.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Review
- Lappaconitine, a C18-diterpenoid alkaloid, exhibits antihypersensitivity in chronic pain through stimulation of spinal dynorphin A expression.Psychopharmacology · 2018Article
- Human D-Amino Acid Oxidase: Structure, Function, and Regulation.Frontiers in molecular biosciences · 2018Review
- Biochemical Properties of Human D-amino Acid Oxidase Variants and Their Potential Significance in Pathologies.Frontiers in molecular biosciences · 2018Review
- Autocrine Interleukin-10 Mediates Glucagon-Like Peptide-1 Receptor-Induced Spinal Microglial β-Endorphin Expression.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Blood levels of D-amino acid oxidase vs. D-amino acids in reflecting cognitive aging.Scientific reports · 2017Article
- Mouse d-Amino-Acid Oxidase: Distribution and Physiological Substrates.Frontiers in molecular biosciences · 2017Review
- D-Amino acid oxidase inhibitors based on the 5-hydroxy-1,2,4-triazin-6(1H)-one scaffold.Bioorganic & medicinal chemistry letters · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeSpinal reactive oxygen species (ROS) are critically involved in chronic pain. D-Amino acid oxidase (DAAO) oxidizes D-amino acids such as D-serine to form the byproduct hydrogen peroxide without producing other ROS. DAAO inhibitors are specifically analgesic in tonic pain, neuropathic pain and cancer pain. This study examined the role of spinal hydrogen peroxide in pain and the mechanism of the analgesic effects of DAAO inhibitors. EXPERIMENTAL APPROACH: Formalin-induced pain behaviours and spinal hydrogen peroxide levels were measured in rodents. KEY
resultsFormalin injected into the paw increased spinal hydrogen peroxide synchronously with enhanced tonic pain; both were effectively prevented by i.t. fluorocitrate, a selective astrocyte metabolic inhibitor. Given systemically, the potent DAAO inhibitor CBIO (5-chloro-benzo[d]isoxazol-3-ol) blocked spinal DAAO enzymatic activity and specifically prevented formalin-induced tonic pain in a dose-dependent manner. Although CBIO maximally inhibited tonic pain by 62%, it completely prevented the increase in spinal hydrogen peroxide. I.t. catalase, an enzyme specific for decomposition of hydrogen peroxide, completely depleted spinal hydrogen peroxide and prevented formalin-induced tonic pain by 65%. Given systemically, the ROS scavenger PBN (phenyl-N-tert-butylnitrone) also inhibited formalin-induced tonic pain and increase in spinal hydrogen peroxide. Formalin-induced tonic pain was potentiated by i.t. exogenous hydrogen peroxide. CBIO did not increase spinal D-serine level, and i.t. D-serine did not alter either formalin-induced tonic pain or CBIO's analgesic effect. CONCLUSIONS AND IMPLICATIONS: Spinal hydrogen peroxide is specifically and largely responsible for formalin-induced pain, and DAAO inhibitors produce analgesia by blocking spinal hydrogen peroxide production rather than interacting with spinal D-serine.
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