title: Involvement of spinal lipoxygenase metabolites in hyperalgesia and opioid tolerance.
abstract: This study investigated role of spinal lipoxygenase metabolites in induction of hyperalgesia and development of opioid analgesic tolerance. In the rat, nociception was measured using formalin and tail-flick tests. Intrathecal administration of leukotriene receptor agonist (LTB4) augmented the second phase of the formalin response and marginally increased sensitivity to acute thermal stimulation in the tail-flick test, responses suppressed by 6-(6-(3R-hydroxy-1E,5Z-undecadien-1-yl)-2-pyridinyl)-1,5S-hexanediol (U75302), a leukotriene BLT receptor antagonist. Treatment with 15-hydroxyperoxyeicosatetranoic acid (HPETE) increased phase II formalin activity, but had no effect on tail-flick responses. 12-HPETE failed to produce an effect in either nociceptive test. In the second part of this study, chronic spinal morphine for 5 days produced progressive decline in morphine antinociception and loss in analgesic potency. These effects were attenuated by co-administration of morphine with selective and nonselective lipoxygenase inhibitors. These results suggest involvement of lipoxygenase metabolites in both pain modulation and induction of opioid tolerance at the spinal level.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Tuan
authors.initials: T
authors.lastname: Trang
authors.forename: Benjamin
authors.initials: B
authors.lastname: McNaull
authors.forename: Remi
authors.initials: R
authors.lastname: Quirion
authors.forename: Khem
authors.initials: K
authors.lastname: Jhamandas
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D044950:Flavanones / Q000494:pharmacology; D005557:Formaldehyde; D006614:Hindlimb; D006930:Hyperalgesia / Q000201:enzymology* / Q000517:prevention & control; D007278:Injections, Spinal; D007975:Leukotriene B4 / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology; D008054:Lipid Peroxides / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D016227:Benzoquinones; D044950:Flavanones; D015289:Leukotrienes; D008054:Lipid Peroxides; D016859:Lipoxygenase Inhibitors; D005557:Formaldehyde; D007975:Leukotriene B4; C006680:baicalein; C021201:12-HPETE; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D009020:Morphine; D009637:Masoprocol; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D008084:Lipoxygenase