Contributions of spinal D-amino acid oxidase to chronic morphine-induced hyperalgesia.

Abstract

Spinal D-amino acid oxidase (DAAO) is an FAD-dependent peroxisomal flavoenzyme which mediates the conversion of neutral and polar D-amino acids (including D-serine) to the corresponding α-keto acids, and simultaneously produces hydrogen peroxide and ammonia. This study has aimed to explore the potential contributions of spinal DAAO and its mediated hydrogen peroxide/D-serine metabolism to the development of morphine-induced hyperalgesia. Bi-daily subcutaneous injections of morphine to mice over 7 days induced thermal hyperalgesia as measured by both the hot-plate and tail-immersion tests, and spinal astroglial activation with increased spinal gene expression of DAAO, glial fibrillary acidic protein (GFAP) and pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)). Subcutaneous injections of the potent DAAO inhibitor CBIO (5-chloro-benzo[D]isoxazol-3-ol) prevented and reversed the chronic morphine-induced hyperalgesia. CBIO also inhibited both astrocyte activation and the expression of pro-inflammatory cytokines. Intrathecal injection of the hydrogen peroxide scavenger PBN (phenyl-N-tert-butylnitrone) and of catalase completely reversed established morphine hyperalgesia, whereas subcutaneous injections of exogenous D-serine failed to alter chronic morphine-induced hyperalgesia. These results provided evidence that spinal DAAO and its subsequent production of hydrogen peroxide rather than the D-serine metabolism contributed to the development of morphine-induced hyperalgesia.

• Authors: Shuai Ma, Xin-Yan Li, Nian Gong, Yong-Xiang Wang
• Journal: Journal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 116 Pg. 131-8 (Dec 10 2015) ISSN: 1873-264X [Electronic] England
• PMID: 25850373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Analgesics, Opioid
• Morphine
• D-Amino-Acid Oxidase

Topics

• Analgesics, Opioid (administration & dosage)
• Animals
• D-Amino-Acid Oxidase (metabolism)
• Female
• Hyperalgesia (drug therapy, enzymology)
• Injections, Spinal
• Injections, Subcutaneous
• Mice
• Morphine (administration & dosage)
• Pain Measurement (drug effects)