Novel function of bovine milk-derived lactoferrin on antinociception mediated by mu-opioid receptor in the rat spinal cord.
Lactoferrin (LF) is a multifunctional protein that is found in milk, neutrophils, and other biological fluids. Although LF and the LF receptor have been identified in the central nervous system (CNS), the physiological role of LF remains unknown. We found that bovine milk-derived LF (BLF) reduces nociception in various pain models, as shown by the formalin test, hot plate test, and acetic acid writhing test in rats. Intraperitoneal (i.p.) administration of BLF significantly inhibited nociception in these pain models. These antinociceptive effects were also confirmed in BLF-fed rats. The antinociceptive effects of BLF were blocked by naloxone treatment, even though prostaglandin E(2) (PGE(2)) production in the ascites fluid that accumulated during the writhing test was not affected by BLF. Intrathecal (i.t.) application of BLF caused marked antinociceptive effects that were reversed by co-administration of a specific mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-NH(2) (CTOP), or by naloxone during the formalin test. We conclude that LF possesses mu-opioid receptor-mediated antinociceptive activity in the spinal cord.
Hayashida
Ken-ichiro
K
Department of Veterinary Physiology, Faculty of Agriculture, Tottori University, Tottori 680-0945, Japan.
Takeuchi
Takashi
T
Shimizu
Hirohiko
H
Ando
Kunio
K
Harada
Etsumori
E
D000700:Analgesics / Q000008:administration & dosage* / Q000302:isolation & purification; D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D007781:Lactoferrin / Q000008:administration & dosage* / Q000302:isolation & purification; D008297:Male; D008892:Milk / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology
D000700:Analgesics; D017450:Receptors, Opioid, mu; D007781:Lactoferrin