title: Spinal D-amino acid oxidase contributes to mechanical pain hypersensitivity induced by sleep deprivation in the rat.
abstract: We studied the hypothesis that spinal d-amino acid oxidase (DAAO) that is expressed in astrocytes and that has been reported to promote tonic pain in various pathophysiological conditions plays a role in 'physiological' pain hypersensitivity induced by rapid eye movement sleep deprivation (REMSD). The experiments were performed in healthy rats with a chronic intrathecal (i.t.) catheter. Pain behavior was assessed by determining limb withdrawal response to repetitive stimulation of the hind paw with a calibrated series of monofilaments. REMSD of 48 h duration produced a significant mechanical hypersensitivity. At 48 h of REMSD, the animals were treated i.t. with a DAAO inhibitor or vehicle. Three structurally different DAAO inhibitors were tested in this study: 6-chlorobenzo[d]isoxazol-3-ol (CBIO), sodium benzoate, and 5-methylpyrazole-3-carboxylic acid (AS-057278). CBIO (1-3 μg), sodium benzoate (30-100 μg) and AS-057278 (3-10 μg) produced dose-related antihypersensitivity effects in sleep-deprived animals. In control animals (with no sleep deprivation), the currently used doses of DAAO inhibitors failed to produce significant changes in mechanically evoked pain behavior. The results indicate that among spinal pain facilitatory mechanisms that contribute to the sleep deprivation-induced mechanical pain hypersensitivity is DAAO, presumably due to production of reactive oxygen species, such as hydrogen peroxide, an endogenous agonist of the pronociceptive TRPA1 ion channel.
authors: King's Lab, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China; Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.
authors: Hong
authors: H
authors: Wei
authors: Nian
authors: N
authors: Gong
authors: Jin-Lu
authors: JL
authors: Huang
authors: Hui
authors: H
authors: Fan
authors: Ai-Niu
authors: AN
authors: Ma
authors: Xin-Yan
authors: XY
authors: Li
authors: Yong-Xiang
authors: YX
authors: Wang
authors: Antti
authors: A
authors: Pertovaara
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010146:Pain / Q000209:etiology*; D017288:Pain Threshold / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012892:Sleep Deprivation / Q000150:complications*; D012895:Sleep, REM; D013116:Spinal Cord / Q000201:enzymology*
chemical_list: D011720:Pyrazoles; D003605:D-Amino-Acid Oxidase; C005210:5-methylpyrazole-3-carboxylic acid
keywords: 5-methylpyrazole-3-carboxylic acid; 6-chlorobenzo[d]isoxazol-3-ol; AS-057278; Astrocyte; CBIO; DAAO; Hydrogen peroxide; Pain hypersensitivity; REM; REM sleep deprivation; REMSD; ROS; Spinal dorsal horn; TRPA1; d-amino acid oxidase; rapid eye movement; rapid eye movement sleep deprivation; reactive oxygen species; transient receptor potential ankyrin 1