title: Lactoferrin enhances peripheral opioid-mediated antinociception via nitric oxide in rats.
abstract: Lactoferrin (LF) is a multifunctional protein found in various biological fluids. However, the peripheral action of lactoferrin remains unknown. In this study, peripherally applied bovine lactoferrin showed antinociceptive effect that was reversed by a mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-NH(2) (CTOP), or by a nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), but not by an inactive enantiomer of L-NAME, N(G)-nitro-D-arginine methyl ester (D-NAME), during phase 1 and phase 2 in the rat formalin test. Peripheral coadministration of a micro-opioid receptor agonist, morphine, with subeffective dose of bovine lactoferrin produced a potentiated antinociceptive effect compared to that of morphine alone during both phases in the formalin test. This potentiated antinociception by morphine with bovine lactoferrin was reversed by CTOP or by L-NAME. These results suggest that bovine lactoferrin exerts an antinociceptive activity via potentiation of the peripheral micro-opioidergic system, and that nitric oxide (NO) is involved in this potentiation.
authors.affiliation: Department of Veterinary Physiology, Faculty of Agriculture, Tottori University, Tottori 680-0945, Japan
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Hayashida
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Etsumori
authors.initials: E
authors.lastname: Harada
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007781:Lactoferrin / Q000494:pharmacology*; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000700:Analgesics; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009569:Nitric Oxide; D007781:Lactoferrin