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

Epidurally administered morphine is useful in the management of postoperative or cancer pain, and a reliable method which can produce prolongation of analgesia with a single dose may be very useful. We synthesized a polyethylene glycol-morphine (PEG-morphine) composites and examined the duration of analgesia after a single epidural administration dose of this agent in the rat. The molecular weight of PEG was functionally evaluated. PEG-morphine was injected surgically along the epidural space. Morphine in doses of 2.5, 5.0 and 7.5 mg and PEG only were administered. A second group of animals received intramuscular injections of PEG-morphine (5.0mg). Animals were then tested for analgesia using the tail-flick test. The antinociceptive effect of 7.5mg was significantly longer than that of 2.5mg or 5.0mg. Neither PEG alone nor intramuscular administration of PEG-morphine induced antinociceptive effect. Sensory blockade was reversible and the animal appeared to have normal sensory perception. We conclude that the antinociceptive effect of morphine is dose-dependent and its duration can be prolonged when administered as a PEG-morphine composite in the epidural space.
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PMID:[Prolonged antinociceptive effect after epidural injection of polyethylene glycol-morphine composites in rats]. 884 82

Poly(ethylene glycol), or PEG, conjugation to proteins and peptides is a growing technology used to enhance efficacy of therapeutics. This investigation assesses pharmacodynamic and pharmacokinetic characteristics of PEG-conjugated [D-Pen2,D-Pen5]-enkephalin (DPDPE), a met-enkephalin analog, in rodent (in vivo, in situ) and bovine (in vitro) systems. PEG-DPDPE showed increased analgesia (i.v.) compared with nonconjugated form (p < 0.01), despite a 172-fold lower binding affinity for the delta-opioid receptor. [125I]PEG-DPDPE had a 36-fold greater hydrophilicity (p < 0.01) and 12% increase in the unbound plasma protein fraction (p < 0.01), compared with [(125)I]DPDPE. [125I]PEG-DPDPE had a 2.5-fold increase in elimination half-life (p < 0.01), 2.7-fold decrease in volume of distribution (p < 0.01), and a 7-fold decrease in plasma clearance rate (p < 0.01) to [125I]DPDPE. Time course distribution showed significant concentration differences (p < 0.01) in plasma, whole blood, liver, gallbladder, gastrointestinal (GI) content, GI tract, kidneys, spleen, urine, and brain (brain, p < 0.05), between the conjugated and nonconjugated forms. Increased brain uptake of [(125)I]PEG-DPDPE corresponded to analgesia data. [125I]PEG-DPDPE in brain was shown to be 58.9% intact, with 41.1% existing as [125I]DPDPE (metabolite), whereas [125I]DPDPE was 25.7% intact in the brain (at 30 min). In vitro P-glycoprotein affinity was shown for [125I]DPDPE (p < 0.01) but not shown for [125I]PEG-DPDPE. In vitro saturable uptake, with 100 microM DPDPE, was shown for [125I]PEG-DPDPE (p < 0.05). In this study, PEG-conjugated DPDPE seems to act as a prodrug, enhancing peripheral pharmacokinetics, while undergoing hydrolysis in the brain and allowing nonconjugated DPDPE to act at the receptor.
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PMID:Pharmacodynamic and pharmacokinetic characterization of poly(ethylene glycol) conjugation to met-enkephalin analog [D-Pen2, D-Pen5]-enkephalin (DPDPE). 1145 51

The objectives of this study were to examine the effect of poly(ethylene glycol) (PEG) conjugation on the tyrosine residues of biphalin to determine the proper size PEG for optimal efficacy and investigate the antinociceptive profile of PEG-biphalin against biphalin via three routes of administration. All antinociception evaluations were made using a radiant-heat tail flick analgesia meter. (2 kDa)(2) PEG-biphalin was identified as the optimal size of PEG to enhance the antinociceptive profile following intravenous administration of 685 nmol kg(-1) of biphalin or PEG-biphalin [(1 kDa)(2), (2 kDa)(2), (5 kDa)(2), (12 kDa)(2), (20 kDa)(2)]. (2 kDa)(2) PEG-biphalin displayed an area under the curve (AUC) approximately 2.5 times that of biphalin with enhanced analgesia up to 300 min postinjection. (2 kDa)(2) PEG-biphalin was equipotent to biphalin following intracerebroventricular administration (0.4 nmol kg(-1)). Both biphalin and (2 kDa)(2) PEG-biphalin were effectively antagonized with naloxone (10 mg kg(-1)) and a partial antagonistic effect was seen following pretreatment with naltrindole (20 mg kg(-1)). (2 kDa)(2) PEG-biphalin showed significantly increased potency (A(50)) when administered intravenously and subcutaneously. Additionally, (2 kDa)(2) PEG-biphalin demonstrated a significantly enhanced antinociceptive profile (AUC) via all routes of administration tested. These findings indicate that PEG conjugation to biphalin retains opioid-mediated effects observed with biphalin and is a valuable tool for eliciting potent, sustained analgesia via parenteral routes of administration.
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PMID:Conjugation of low molecular weight poly(ethylene glycol) to biphalin enhances antinociceptive profile. 1282 Jan 42

Microemulsion systems possessing a potentially improved skin bioavailability of lidocaine were designed and explored for some characteristics. The existence of microemulsion regions was investigated in quaternary systems composed of glyceryl oleate+polyoxyl 40 fatty acid derivatives (surfactants)/tetraglycol (co-surfactant)/isopropyl palmitate/water by constructing pseudo-ternary phase diagrams at fixed co-surfactant/surfactants (CoS/S) ratios. Light scattering measurements used to determine the diameter of the internal phase revealed that lidocaine in the microemulsions increased the droplet size, implying a drug tendency to accumulate in the interfacial layers. Percutaneous penetration studies using rat skin in vitro showed that the transdermal flux of lidocaine was significantly improved by microemulsion composed of the glyceryl oleate-PEG-40 stearate combination rather than glyceryl oleate-PEG-40 hydroxylated castor oil. Two principal factors were found to govern the transdermal penetration of lidocaine from the microemulsion: water content and the CoS/S ratio. By analyzing skin layers (epidermis and dermis) for lidocaine content, significantly higher concentrations were found after rats were treated in vivo with liquid microemulsions (CoS/S=1.8, 30 wt.% water) or patches compared to those measured after application of EMLA cream. It has been suggested, therefore, that these microemulsions loaded with lidocaine would provide adequate analgesia in relatively shorter periods of time.
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PMID:New microemulsion vehicle facilitates percutaneous penetration in vitro and cutaneous drug bioavailability in vivo. 1498 Jul 66

The aim of this study was to examine the effect of ketoprofen used in preemptive analgesia on the intensity of pain and requirement for analgesics in the perioperative period. Sixty patients scheduled for elective lumbar disc prolapse surgery were randomly divided into two groups. In the PRE group (n = 30) ketoprofen was administered one hour before incision. In the POST group ( n = 30) ketoprofen was used immediately after the surgery. The operation was performed under general anesthesia. Postoperative analgesia was realized by NCA (Nurse Controlled Analgesia) and the "required" dose of ketoprofen was 100 mg. After the operation, pain intensity was measured using visual-analog scale (VAS), ketoprofen requirements, the time to the first dose of ketoprofen, and levels of prostaglandin E(2) (PEG(2)) in blood serum were compared. There were no differences between the groups in the VAS pain scores, and levels of PGE(2) in blood serum. However, in patients of PRE group who had received preemptive analgesia, a significantly lower total consumption of ketoprofen, as compared with POST group, was observed between 12th and 36th postoperative hours. It was also found that the time which elapsed between the end of the operation and the first NCA activation was significantly shorter in the PRE group, as compared with the POST group. The results of our study confirm the possibility of modifying the nociception process in the perioperative period through preemptive analgesia by ketoprofen.
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PMID:Influence of pre-operative ketoprofen administration (preemptive analgesia) on analgesic requirement and the level of prostaglandins in the early postoperative period. 1559 42

The aim of this study is to evaluate oral administration of poly (butylcyanoacrylate) nanoparticulate delivery systems (PBCA-NDSs), double-coated with Tween 80 and poly (ethylene) glycol (PEG) 20000 for brain delivery of hexapeptide dalargin, an anti-nociceptive peptide that does not cross blood-brain barrier (BBB) by itself. Studies have proven the brain uptake of Tween 80 overcoated nanoparticles after intravenous administration, but studies for brain delivery of nanoparticles after oral administration had been limited due to reduced bioavailability of nanoparticles and extensive degradation of the peptide and/or nanoparticles by gastrointestinal enzymes. To address this problem, dalargin-loaded PBCA-NDS were successively double-coated with Tween 80 and PEG 20000 in varied concentrations of up to 2% each. Measurement of in vivo central anti-nociceptive effect of dalargin along with a dose response curve was obtained by the tail flick test following the oral administration of PBCA-NDSs to mice. Results from the tail flick test indicated that significant dalargin-induced analgesia was observed from PBCA-NDSs with double-coating of Tween and PEG in comparison with single-coating of either Tween or PEG. Hence, it could be concluded that surface coated PBCA-NDS can be used successfully for brain targeting of dalargin or other peptides administered orally. However, further studies are required to elucidate the exact transport mechanism of PBCA-NDSs from gastrointestinal tract to brain.
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PMID:Double-coated poly (butylcynanoacrylate) nanoparticulate delivery systems for brain targeting of dalargin via oral administration. 1585 53

We aimed at assessing the effect of using a "Funada-kit II" device during laparoscopy-assisted percutaneous endoscopic gastrostomy (Lap-PEG), by reviewing 29 cases of Lap-PEG we performed from 2001 to 2011. We started using the "Funada-kit II" (CREATE MEDIC CO., Kanagawa, Japan) device with two parallel needles to puncture the stomach and assist suturing the anterior gastric wall to the anterior abdominal wall during Lap-PEG in 2011 (F-PEG). By introducing a loop through the lumen of one needle which allows placement of a suture introduced through the lumen of the other needle. Once repeated, the stomach can be pexied at two points, approximately 2 cm apart. We compared Lap-PEG (n = 23) with F-PEG (n = 6) where the mean ages and weights at surgery and sex ratios were similar. All cases were uneventful without intraoperative complications, although one postoperative wound infection occurred in a Lap-PEG case. There were no differences in the duration of analgesia, time taken to commence tube feeding, and return to full feeding. However, mean operating time was significantly shorter in F-PEG (28.1 min) versus Lap-PEG (46.1 min) p < 0.05. As per results F-PEG would appear to be as safe as Lap-PEG, but much quicker.
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PMID:Laparoscopy-assisted percutaneous endoscopic gastrostomy using a "Funada-kit II" device. 2318 62

We have formulated hydrophobic curcurmin [1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] into stable nanoparticle suspensions (nanocurcumin) to overcome its relatively low bioavailability, high rate of metabolism, and rapid elimination and clearance from the body. Employing the curcumin nanoformulations as the platform, we discovered that curcumin has the potential to alleviate morphine tolerance. The two types of stable polymeric nanoparticles, poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), and the hybrid of the two were generated using flash nanoprecipitation integrated with spray drying. The optimized formulations have high drug loading (>45%), small particles size with narrow distribution, and controlled surface properties. Mice behavioral studies (tail-flick and hot-plate tests) were conducted to verify the effects of nanocurcumin on attenuating morphine tolerance. Significant analgesia was observed in mice during both tail-flick and hot-plate tests using orally administered nanocurcumin following subcutaneous injections of morphine. However, unformulated curcumin at the same dose showed no effect. Compared with PEGylated nanocurcumin, negatively charged PLGA nanoparticles showed better functionality.
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PMID:Orally administered nanocurcumin to attenuate morphine tolerance: comparison between negatively charged PLGA and partially and fully PEGylated nanoparticles. 2419 58

Peripheral nerve blockade (PNB) is a conventional strategy for the management of acute postoperative pain. However, the short duration of the associated analgesia and the potential systemic toxicity due to the low molecular weights of local anesthetics limit their application. Methods: An in situ forming injectable Gel-microsphere (Gel-MS) system consisting of PLGA-PEG-PLGA Gel (Gel) and Gel-immobilized bupivacaine-loaded microsphere (MS/BUP) was prepared for precision-guided long-acting analgesia. A series of in vitro characterizations, such as scanning electron microscopy, rheology analysis, confocal laser scanning microscopy, drug release, and erosion and degradation, were carried out. After that, the in vivo analgesia effect of the Gel-MS system, the immobilization effect of Gel on the MS, and biocompatibility of the system were evaluated using a sciatic nerve block model. Results: The BUP release from the Gel-MS system was regulated by both the inner MS and the outer Gel matrix, demonstrating sustained BUP release in vitro for several days without an initial burst release. More importantly, incorporation of the Gel immobilized the MS and hindered the diffusion of MS from the injection site because of its in situ property, which contributed to a high local drug concentration and prevented systemic side effects. In vivo, a single injection of Gel-MS/BUP allowed rats to maintain sensory and motor blockade significantly longer than treatment with MS/BUP (P < 0.01) or BUP-loaded Gel (Gel-BUP, P < 0.01). Histopathological results demonstrated the excellent biodegradability and biocompatibility of the Gel-MS system without neurotoxicity. Conclusion: This precision-guided long-acting analgesia, which provides an in situ and sustained release of BUP, is a promising strategy for long-acting analgesia, and could represent a potential alternative for clinical pain management.
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PMID:Precision-guided long-acting analgesia by Gel-immobilized bupivacaine-loaded microsphere. 2993 Jul 33