title: Removal of polysialylated neural cell adhesion molecule increases morphine analgesia and interferes with tolerance in mice.
abstract: Neurons that express high levels of polysialylated neural cell adhesion molecule (PSA-NCAM) in adult spinal substantia gelatinosa also express the μ-opioid receptor. While PSA removal from NCAM by spinal intrathecal injection of endoneuraminidase-N (endo-N) did not detectably change opioid receptor expression, morphine-induced analgesia was significantly increased. This analgesic strengthening was detected as early as 15 min after endo-N treatment and persisted for at least 7 days. In addition, the tolerance that develops with chronic morphine treatment was overcome in the absence of PSA. Interestingly, the same effects on analgesia and tolerance were also produced by selective deletion of the NCAM-180 isoform.
authors.affiliation: Department of Cell Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. a-el-maarouf@ski.mskcc.org
authors.forename: Abderrahman
authors.initials: A
authors.lastname: El Maarouf
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kolesnikov
authors.forename: Gavril
authors.initials: G
authors.lastname: Pasternak
authors.forename: Urs
authors.initials: U
authors.lastname: Rutishauser
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal; D004347:Drug Interactions; D004361:Drug Tolerance / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006026:Glycoside Hydrolases / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000172:deficiency; D010147:Pain Measurement / Q000379:methods; D017450:Receptors, Opioid, mu / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013376:Substantia Gelatinosa / Q000187:drug effects / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D017450:Receptors, Opioid, mu; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D009020:Morphine; D006026:Glycoside Hydrolases; C090534:endo-alpha-sialidase