title: Spinal D-amino acid oxidase contributes to neuropathic pain in rats.
abstract: D-amino acid oxidase (DAO) is an enzyme catalyzing oxidative deamination of neutral and polar d-amino acids and is expressed in the kidneys, liver, and central nervous system (CNS) including the spinal cord. We have previously demonstrated that DAO gene deletion/mutation by using mutant ddY/DAO(-/-) mice and systemic administration of the DAO inhibitor sodium benzoate blocked formalin-induced hyperalgesia in mice. In this study, we further investigated the potential role of DAO in neuropathic pain in a rat model of tight L(5)/L(6) spinal nerve ligation. After L(5)/L(6) spinal nerve ligation, the mRNA expression (measured by real-time quantitative polymerase chain reaction) and enzyme activity (measured by a colorimetric method) of DAO in the lumbar spinal cord were markedly increased, in agreement with the development of neuropathic pain (mechanical allodynia). Intraperitoneal injection of sodium benzoate (400 mg/kg) specifically blocked mechanical allodynia in neuropathic rats and formalin-induced hyperalgesia but did not suppress acute pain responses in the tail-flick test or formalin test. Systemic injection of sodium benzoate also inhibited DAO activity in the lumbar spinal cord of rats. Furthermore, direct intrathecal (spinal cord) injection of benzoate (30 mug/rat) specifically blocked spinal nerve ligation-induced mechanical allodynia in neuropathic rats and formalin-induced hyperalgesia (but not acute pain) in the formalin test. Based on the above results, we conclude that spinal DAO plays a pronociceptive (rather than an antinociceptive) role and might be a target molecule for the treatment of chronic pain of neuropathic origin.
authors.affiliation: King's Laboratory, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Zhao
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Gao
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Nie
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Zhou
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000818:Animals; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy / Q000201:enzymology; D017116:Low Back Pain / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy / Q000201:enzymology*; D010147:Pain Measurement; D017288:Pain Threshold; D051381:Rats; D017208:Rats, Wistar; D020160:Sodium Benzoate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013116:Spinal Cord / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D003605:D-Amino-Acid Oxidase; D020160:Sodium Benzoate