Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Degranulation of polymorphonuclear (PMN) granulocytes, complement activation, and the endocrine metabolic response to hysterectomy were compared in two groups of patients receiving either general anaesthesia (GA group) or combined epidural analgesia and general anaesthesia (GAE group). The B-leucocyte and the cortisol responses were attenuated in the GAE group. There was no sign of complement activation. The post-operative rise in elastase-alpha-1-proteinase levels 4 h post-operatively on the first, second and third post-operative days was similar in the two groups. Plasma lactoferrin values were significantly elevated 4 h post-operatively and reached pre-operative values on Day 1 in both groups. Attenuation of the surgical stress response during uncomplicated hysterectomy did not influence the post-operative increase in proteinase activity. Mediators generated at the site of surgical trauma may account for the PMN degranulation observed after major surgery.
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PMID:Attenuation of intra-operative surgical stress response has no influence on post-operative degranulation of polymorphonuclear granulocytes. 168 47

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.
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PMID:Lactoferrin enhances opioid-mediated analgesia via nitric oxide in the rat spinal cord. 1285 13

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.
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PMID:Oral administration of lactoferrin inhibits inflammation and nociception in rat adjuvant-induced arthritis. 1503 42

Lactoferrin (LF) is a multifunctional protein that is widely found in milk, blood, and other biological fluids. In the present study, we investigated the possibility that LF may block a tolerance to morphine-induced analgesia in the mouse. The nociceptive effect of bovine milk-derived LF (bLF) was estimated in the mouse tail-flick test. Although an intraperitoneal (100 mg/kg) or an oral (300 mg/kg) administration of bLF did not show remarkable analgesia, a combination with intraperitoneal administration of morphine (3 mg/kg) strikingly enhanced morphine-induced analgesia. Moreover, repeated administration of morphine at doses of 3 mg/kg (ip) or 5 mg/kg (ip) caused a tolerance to the morphine on the 5th or 7th day, respectively. In contrast, the combination of bLF (100 mg/kg, ip) with morphine (3 mg/kg, ip) retarded the development of tolerance to the 9th day, although bLF did not show any effect on the mice that had obtained tolerance to morphine. Furthermore, the potentiative effect of bLF was partially blocked by pre-treatment with N(G)-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) inhibitor, and completely blocked by 7-nitroindazole (7-NI), a selective neuronal NOS (nNOS) inhibitor. Methylene blue (MB), a guanylate cyclase (GC) inhibitor, also dose-dependently prevented the potentiative effect of bLF. These results suggest that bLF selectively activates nNOS and then accelerates NO production. The increased NO in turn modulates the GC activity and finally enhances the endogenous opioid system via cyclic guanosine monophosphate production. We conclude that bLF may block the development of tolerance to morphine in mice, possibly via the selective activation of nNOS.
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PMID:Milk-derived lactoferrin may block tolerance to morphine analgesia. 1638 99