lactoferrin and Pain

Increased viscosity and raised lactoferrin, trypsin and protein concentrations in selectively aspirated pancreatic secretion, prompted us to try depot secretin therapy in patients with advanced chronic recurrent pancreatitis without pancreatic duct obstruction or pancreatic pseudocysts. The idea behind this approach was that it might "wash out" the sticky, protease-rich secretion. In a randomized double-blind trial we administered depot secretin at doses of 800 CU by subcutaneous injection twice daily for 7 days. Pancreatic secretion from the treatment group had significantly lower viscosities and lactoferrin and trypsin concentrations than in the placebo group. There was also significant pain relief. Depot secretin therapy appears to offer an alternative approach to the management of advanced chronic recurrent pancreatitis without pancreatic duct obstruction or pseudocysts.

Topics: Amylases; Chronic Disease; Clinical Trials as Topic; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Lactoferrin; Male; Middle Aged; Pain; Pancreatic Juice; Pancreatitis; Random Allocation; Recurrence; Secretin; Trypsin; Viscosity

Central pain (CP) is a common clinical problem in patients with spinal cord injury (SCI). Recent studies found the pathogenesis of CP was related to the remodeling of the brain. We investigate the roles of iron overload and subsequent oxidative stress in the remodeling of the brain after SCI.. We established a rat model of central pain after SCI. Rats were divided randomly into four groups: SCI, sham operation, SCI plus deferoxamine (DFX) intervention, and SCI plus nitric oxide synthase (NOS) inhibitor treatment. Pain behavior was observed and thermal pain threshold was measured regularly, and brain levels of iron, transferrin receptor 1 (TfR1), ferritin (Fn), and lactoferrin (Lf), were detected in the different groups 12 weeks after establishment of the model.. Rats demonstrated self-biting behavior after SCI. Furthermore, the latent period of thermal pain was reduced and iron levels in the hind limb sensory area, hippocampus, and thalamus increased after SCI. Iron-regulatory protein (IRP) 1 levels increased in the hind limb sensory area, while Fn levels decreased. TfR1 mRNA levels were also increased and oxidative stress was activated. Oxidative stress could be inhibited by ferric iron chelators and NOS inhibitors.. SCI may cause intracranial iron overload through the NOS-iron-responsive element/IRP pathway, resulting in central pain mediated by the oxidative stress response. Iron chelators and oxidative stress inhibitors can effectively relieve SCI-associated central pain.

Topics: Animals; Brain; Female; Ferritins; Iron; Iron Overload; Iron Regulatory Protein 1; Lactoferrin; Malondialdehyde; Oxidative Stress; Pain; Pain Measurement; Pain Threshold; Rats, Sprague-Dawley; Receptors, Transferrin; Spinal Cord Injuries; Superoxide Dismutase

This study aimed to investigate the effect of prolonged administration of bovine milk lactoferrin (bLF) on hyperalgesia and allodynia in a rat model of neuropathic pain and to determine the involvement of c-Fos, TNF-alpha, nitric oxide and opioidergic systems in this effect.. Neuropathic pain was induced in rats by loose ligation of the right sciatic nerve and evaluated by tests measuring the mechanical and thermal hyperalgesia and allodynia. bLF (50, 100, and 200mg/kg) alone or in combination with opioidergic antagonists were administered intraperitoneally to the rats with neuropathic pain. c-Fos and NADPH-d immunocytochemistry and Western blotting for TNF-alpha, iNOS and nNOS were performed in the lumbar spinal cord of rats. Plasma TNF-alpha levels were determined with ELISA.. Prolonged, but not single, administration of bLF produced antihyperalgesic and antiallodynic effects in neuropathic rats. Pretreatment with opioidergic antagonists significantly decreased this effect. Prolonged administration of bLF decreased c-Fos and NADPH-d immunoreactivity and TNF-alpha and iNOS expressions at 50 and 100mg/kg and nNOS expression at 100mg/kg in the lumbar spinal cord of neuropathic rats. Plasma TNF-alpha levels remained unchanged after bLF treatment.. Prolonged administration of bLF exerts antihyperalgesic and antiallodynic effect in neuropathic rats; down-regulation of both TNF-alpha and iNOS expressions and potentiation of opioidergic system in the lumbar spinal cord can contribute to this effect.

Topics: Animals; Cattle; Down-Regulation; Genes, fos; Lactoferrin; Male; Narcotic Antagonists; Nitric Oxide; Nitric Oxide Synthase Type II; Pain; Rats; Rats, Wistar; Receptors, Opioid; Time Factors; Tumor Necrosis Factor-alpha

PEP1261, a tetrapeptide derivative used in this study, corresponds to residues 39-42 of human lactoferrin. The parent protein lactoferrin is known to exhibit antinociceptive activity and it regulates many aspects of inflammation. This study is aimed to evaluate the antinociceptive and antipyretic activities of PEP1261 in rats. PEP1261 exhibits a significant dose dependent antinociceptive activity with optimal effect at 40 mg/kg body weight (b.w.) (i.p.) in both tail-flick model and acetic acid induced writhing in rats. PEP1261 at the doses of 20 and 40 mg/kg b.w. (i.p.) is also observed to exhibit notable antipyretic effect in lipopolysaccharide-induced pyrexia in rats. In conclusion, the results suggest that PEP1261 possesses antinociceptive and antipyretic activities better than the control peptide KRDS.

Topics: Amino Acid Sequence; Analgesics; Analgesics, Non-Narcotic; Animals; Female; Inflammation; Lactoferrin; Oligopeptides; Pain; Rats; Rats, Wistar

Lactoferrin (LF) is a ubiquitous protein which exists in milk, plasma, synovial fluids, cerebrospinal fluid and other biological fluids. LF is also well known as a natural immunomodulator. Recently, we found that bovine milk-derived LF (BLF) produced micro-opioid receptor-mediated analgesia. In this study, we examined whether oral administration of BLF causes anti-nociceptive and anti-inflammatory effects, and also whether it modulates LPS-induced TNF-alpha and IL-10 production in rat model of rheumatoid arthritis (RA), rat adjuvant arthritis. BLF was administrated once daily, starting 3 hr before (preventive experiment) or 19 days after (therapeutic experiment) adjuvant injection. In both experiments, BLF suppressed the development of arthritis and the hyperalgesia in the adjuvant-injected paw. The single-administered BLF produced a dose-dependent analgesia, which was reversed by naloxone, in the adjuvant arthritis rats. Both repeated and single administration of BLF suppressed TNF-alpha production and increased IL-10 production in the LPS-stimulated adjuvant arthritis rats. These results suggest that orally administered BLF has both preventive and therapeutic effects on the development of adjuvant-induced inflammation and pain. Moreover, the immunomodulatory properties of BLF, such as down-regulation of TNF-alpha and up-regulation of IL-10, could be beneficial in the treatment of RA. Thus, we concluded that LF can be safely used as a natural drug for RA patients suffering from joint pain.

Topics: Administration, Oral; Analysis of Variance; Animals; Arthritis, Experimental; Disease Models, Animal; Inflammation; Interleukin-10; Lactoferrin; Male; Naloxone; Pain; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Lactoferrin (LF) is a multifunctional protein that is found in milk, neutrophils, and other biological fluids, and its receptors have also been identified in the central nervous system. Recently, we found that bovine milk-derived LF (BLF) produced analgesia via a mu-opioid receptor-mediated response in the spinal cord. However, the precise mechanism of this analgesic effect remains unclear. In this study, spinally applied BLF produced analgesia that was reversed by coadministration with a nitric oxide (NO) synthase inhibitor, NG-nitro-l-arginine methyl ester, during phases 1 and 2 in the formalin test. Spinal coadministration of a mu-opioid receptor agonist, morphine, with a subeffective dose of BLF produced a much more highly potentiated analgesia than that produced by morphine alone during phases 1 and 2 in the formalin test. This potentiated analgesia by morphine with BLF was reversed by a mu-opioid receptor antagonist, d-Phe-Cys-Tyr-d-Trp-Orn-Thr-NH2, or by NG-nitro-l-arginine methyl ester. In the tail-flick test, continuous spinal infusion of morphine via an osmotic minipump over 6 days resulted in development of tolerance by day 4, but no tolerance of BLF was observed throughout the experiment. These results suggest that BLF acts as an enhancer of the spinal opioidergic system via an NO-mediated mechanism.

Topics: Analgesics; Animals; Dose-Response Relationship, Drug; Drug Tolerance; Formaldehyde; Lactoferrin; Male; Morphine; Narcotics; Nitric Oxide; Nitric Oxide Synthase; Pain; Rats; Rats, Inbred Strains; Spinal Cord

Topics: Animals; Drug Tolerance; Humans; Lactoferrin; Narcotics; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Pain