Inhibition of D-amino-Acid oxidase activity induces pain relief in mice.
(1). We investigated the effects of inhibiting D: -amino-acid oxidase (DAO) activity on nociceptive responses through the use of mutant ddY/DAO(-) mice, which lack DAO activity, and through the application of a selective inhibitor of DAO, sodium benzoate, in the tail flick test, hot-plate test, formalin test, and acetic acid-induced writhing test. (2). Compared with normal ddY/DAO+ mice, ddY/DAO(- )mice showed significantly prolonged tail withdrawal latency in the tail flick test and licking/jumping latency in the hot-plate test, as well as significantly reduced duration of licking/biting in the late phase of the formalin test and the number of abdominal writhing in the acetic acid-induced writhing test. (3). In addition, we investigated the effects of sodium benzoate in Kunming mice having normal DAO activity. (4). Intravenous administration of sodium benzoate (400 mg/kg) significantly inhibited pain responses of the late phase of the formalin test and abdominal writhing responses in the acetic acid-induced writhing test, with no effects on the early phase flinch responses in the formalin test, nociceptive responses in the tail flick test, or hot-plate test. (5). These results suggest that DAO acts as a pro-nociceptive factor in pain, particularly chronic pain, transmission and modulation, and may be a target for pain treatment.
Zhao
Wenjuan
W
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Konno
Ryuichi
R
Zhou
Xiang-Jun
XJ
Yin
Ming
M
Wang
Yong-Xiang
YX
D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D002908:Chronic Disease; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D020160:Sodium Benzoate / Q000494:pharmacology / Q000627:therapeutic use*
D000700:Analgesics; D004791:Enzyme Inhibitors; C485958:Dao1 protein, mouse; D003605:D-Amino-Acid Oxidase; D020160:Sodium Benzoate