Fentanyl as a synthetic opioid works by binding to the mu-opioid receptor (MOR) in brain areas to generate analgesia, sedation and reward related behaviors. As we know, cerebellum is not only involved in sensory perception, motor coordination, motor learning and precise control of autonomous movement, but also important for the mood regulation, cognition, learning and memory. Previous studies have shown that functional MORs are widely distributed in the cerebellum, and the role of MOR activation in cerebellum has not been reported. The aim of the present study was to investigate the effects of fentanyl on air-puff stimulus-evoked field potential response in the cerebellar molecular layer using in vivo electrophysiology in mice. The results showed that perfusion of 5 μmol/L fentanyl on the cerebellar surface significantly inhibited the amplitude, half width and area under the curve (AUC) of sensory stimulation-evoked inhibitory response P1 in the molecular layer. The half-inhibitory concentration (IC
Animals ; Cerebellum ; Evoked Potentials ; Fentanyl/pharmacology* ; Interneurons ; Mice ; Physical Stimulation

BACKGROUND: Patient-controlled analgesia (PCA) is a widely used method of postoperative analgesia with the advantage of tailored dosing for each individual. In spite of its popularity, there have been few reports on the current state of PCA in Korea. In this study, the data on PCA management and PCA regimens of medical institutions in Korea were collected and analyzed. METHODS: Members of the Korean Society for Anesthetic Pharmacology were questioned as to the state of postoperative PCA management, such as acute pain services (APS) and pain assessment. A list of PCA regimens for each institution was also requested and analyzed. RESULTS: Among 65 hospitals, APS was run in 30 and the severity of postoperative pain was assessed in 60. The safety and efficacy of PCA was evaluated only in 9 hospitals. A total 518 PCA regimens were reported (414, 95 and 9 regimens for intravenous, epidural and other routes, respectively). For intravenous PCA, fentanyl only and fentanyl-ketorolac regimens comprised 33.8 and 30.9% of treatments, respectively. In 95.9% of the regimens, background infusion was used. For epidural PCA, fentanyl-ropivacaine or fentanyl-levobupivacaine regimens made up the majority (47.4 and 13.7%, respectively). CONCLUSIONS: In Korea, APS was used in less than 50% of the hospitals and the evaluation of the safety and efficacy of PCA is not carried out in the majority. Background infusion, known to have little advantage in most cases, was widely used in intravenous PCA.
Analgesia ; Analgesia, Patient-Controlled* ; Fentanyl ; Korea* ; Pain Clinics ; Pain Measurement ; Pain, Postoperative ; Passive Cutaneous Anaphylaxis ; Pharmacology

Analgesia ; Atrial Fibrillation ; surgery ; Catheter Ablation ; methods ; Conscious Sedation ; Fentanyl ; pharmacology ; Humans ; Hypnotics and Sedatives ; pharmacology ; Midazolam ; pharmacology ; Propofol ; pharmacology ; Prospective Studies

Adult ; Analgesics, Opioid ; pharmacology ; Female ; Fentanyl ; pharmacology ; Humans ; In Vitro Techniques ; Interleukin-6 ; blood ; Male ; Morphine ; pharmacology ; Narcotics ; pharmacology ; Tumor Necrosis Factor-alpha ; analysis

BACKGROUNDOpioid switching is a therapeutic maneuver to improve analgesic response and/or reduce adverse side effects although the underlying mechanisms remain unknown. The µ-opioid receptor (MOR) has an important role in mediating the actions of morphine and other analgesic agents. This study is aimed at exploring the changes of MOR in the periaqueductal gray (PAG) in rats when morphine is substituted for equianalgesic fentanyl.

METHODSForty rats were randomly assigned to five treatment groups: 7 days normal saline group (N group), 7 days fentanyl group (F group), 7 days morphine group (M group), 7 days morphine and 7 days fentanyl-switching group (MF group), and 14 days morphine group (MM group). Rats repeatedly received subcutaneous injections of morphine sulfate (10 mg/kg) or equianalgesic fentanyl sulfate (0.1 mg/kg) twice daily. Rats' antinociceptive response to thermal pain was evaluated by the tail flick latency assay. MOR mRNA and protein expression in the PAG were measured using RT-PCR and Western blotting analyses respectively.

RESULTSThis study showed that after morphine was substituted with fentanyl on day 8, the tail flick latency (TFL) increased from (3.9 ± 0.4) seconds to (11.4 ± 0.4) seconds. The results also demonstrated that both MOR mRNA and protein expression in the PAG of rats in the MF group were less than that in the M group (P < 0.05) but more than that in MM group (P < 0.05).

CONCLUSIONSEquianalgesic fentanyl was still antinociceptive effective in rats with morphine tolerance, which may be due to the switching from morphine to fentanyl attenuating the decline of MOR expression in the PAG of rats.

Analgesics, Opioid ; pharmacology ; Animals ; Drug Tolerance ; Fentanyl ; pharmacology ; Male ; Morphine ; pharmacology ; Periaqueductal Gray ; chemistry ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar ; Receptors, Opioid, mu ; analysis ; genetics

BACKGROUND: Epidural clonidine reduces pain after surgery. The aim of this study was to evaluate the effect of adding low-dose clonidine to continuous epidural local anesthetics and fentanyl on pam relief. METHODS: 100 patients scheduled for gynecologic low abdominal surgery were investigated. All patients were given 10cc of 0.25% bupivacaine with fentanyl 100 ug through epidural catheter. Group I was infused with combined 0.15% bupivacaine and fentanyl 5 ug/ml at a rate of 2cc/hr. Group II was infused with combined 0.15% bupivacaine and fentanyl 5 ug/ml and 150 ug of clonidine at a rate of 2cc/hr. Pain was assessed on a visual analogue pain scale for 2 postoperative days. Changes in blood pressure, heart rate, and incidence of side effects were observed. RESULTS: VAS observed 20min, 1hr, 1day, 2days after operation were significantly lower in Group II than Group I . Blood pressure and heart rates were significantly changed in Group II but not in Group I for 2 hours after epidural injection. The incidence of side effects was similar between Group I and Group II. CONCLUSIONS: Continuous low-dose epidural clonidine infusion reduces blood pressure and heatt rates significantly but enhances postoperative analgesic effect of combined epidural bupivacaine and fentanyl without increased side effects.
Anesthetics ; Anesthetics, Local ; Blood Pressure ; Bupivacaine* ; Catheters ; Clonidine* ; Fentanyl* ; Heart Rate ; Humans ; Incidence ; Injections, Epidural ; Pain Measurement ; Pharmacology

OBJECTIVETo investigate the effect of dexmedetomidine on oxygenation function in adult patients with balanced anesthesia by propofol-fentanyl under one-lung ventilation (OLV).

METHODSTwenty-two patients undergoing thoracic operation were randomly divided into the study group and control group, both receiving propofol and fentanyl balanced anesthesia. In the study group, additional infusion of dexmedetomidine (0.3 µg/kg loading dose, 0.3 µg·kg(-1)·h(-1) maintenance dose) was administered, and the patients in the control group received only normal saline. Arterial blood samples were obtained at 4 time points from each patient during anesthesia for blood gas analysis.

RESULTSIn the study group, the pH values remained stable, the oxygenation index tended to decline progressively, but the incidence of hypoxemia was low; in the control group, the pH value and oxygenation index both declined progressively with a higher incidence of hypoxemia.

CONCLUSIONDexmedetomidine can better maintain the oxygenation function of OLV patients in balanced anesthesia by propofol and fentanyl, and its mechanism may be related to the decreased dose of propofol used.

Adult ; Balanced Anesthesia ; Blood Gas Analysis ; Dexmedetomidine ; pharmacology ; Female ; Fentanyl ; Humans ; Male ; Middle Aged ; One-Lung Ventilation ; Propofol

PURPOSE: Fentanyl was reported to inhibit the alpha1-adrenoceptor agonist-induced contraction. The goal of this in vitro study was to identify the alpha1-adrenoceptor subtype primarily involved in the fentanyl-induced attenuation of phenylephrine-induced contraction in isolated endothelium-denuded rat aorta. MATERIALS AND METHODS: Aortic rings were suspended in order to record isometric tension. Concentration-response curves for phenylephrine (10-9 to 10-5 M) were generated in the presence or absence of one of the following drugs: fentanyl (3x10-7, 10-6, 3x10-6 M), 5-methylurapidil (3x10-8, 10-7, 3x10-7 M), chloroethylclonidine (10-5 M) and BMY 7378 (3x10-9, 10-8, 3x10-8 M). Phenylephrine concentration-response curves were generated in the presence or absence of fentanyl in rings pretreated with either 3x10-9 M prazosin, 10-9 M 5-methylurapidil or 3x10-9 M BMY 7378. RESULTS: Fentanyl (10-6, 3x10-6 M) attenuated phenylephrine-induced contraction in the rat aorta. 5-Methylurapidil and BMY 7378 produced a parallel rightward shift in the phenylephrine concentration-response curve. The pA2 values for 5-methylurapidil and BMY 7378 were estimated to be 7.71 +/- 0.15 and 8.99 +/- 0.24, respectively. Fentanyl (10-6 M) attenuated phenylephrine-induced contraction in rings pretreated with 10-9 M 5-methylurapidil, but did not alter the rings when pretreated with 3x10-9 M BMY 7378. Pretreatment of the rings with chloroethylclonidine showed a 72.9 +/- 2.3% reduction in phenylephrine-induced maximal contraction. CONCLUSION: The results suggest that fentanyl attenuates phenylephrine-induced contraction by inhibiting the pathway involved in the alpha1D-adrenoceptor-mediated contraction of the rat aorta.
Adrenergic alpha-Agonists/*pharmacology ; Adrenergic alpha-Antagonists/*pharmacology ; Animals ; Aorta/*drug effects ; Clonidine/analogs & derivatives/pharmacology ; Fentanyl/*pharmacology ; Male ; Phenylephrine/*pharmacology ; Piperazines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/*drug effects

OBJECTIVETo investigate the roles of sympathetic and vagus nerves in hypotension and bradycardia induced by fentanyl.

METHODSFourteen rabbits were divided into 2 groups: normal and vagotomized rabbits. Rabbits were anesthetized, paralyzed, and artificial ventilated. Right renal sympathetic nerve was exposed and prepared for recording electrical activity. Fentanyl was injected intravenously in incremental doses of 1, 4, 15, 30, and 50 microg/kg at 10 minutes intervals.

RESULTSFentanyl significantly reduced the spontaneous activity of renal sympathetic nerve, mean arterial pressure, and heart rate above a total dose of 20 microg/kg in both normal and vagotomized rabbits. However, normal rabbits spontaneous sympathetic nerve activity and mean arterial pressure were more depressed than vagotomized rabbits at total doses of 50 and 100 microg/kg. There were no significant difference in the reduction of heart rate between normal and vagotomized rabbits.

CONCLUSIONFentanyl induction of bradycardia and hypotension in rabbits is mainly due to depression of sympathetic nerve activity.

Analgesics, Opioid ; pharmacology ; Animals ; Blood Pressure ; drug effects ; Fentanyl ; pharmacology ; Heart Rate ; drug effects ; Kidney ; innervation ; Rabbits ; Sympathetic Nervous System ; drug effects ; physiology ; Vagotomy

OBJECTIVETo study the analgesic effect and safety of fentanyl in neonates receiving mechanical ventilation.

METHODSThirty neonates receiving mechanical ventilation between December 2010 and February 2011 were randomized into drug intervention group and control group (n=15 each). In addition to the conventional treatment for both groups, the drug intervention group received fentanyl as the analgesic treatment. Heart rate, respiratory rate, blood pressure changes, and premature infant pain profile (PIPP) score before treatment and at 30 minutes, 2 hours, and 4 hours after treatment were recorded in both groups. Follow-up visits were performed for these infants after discharge, and the CDCC intellectual development scale for infants was applied to measure mental development index (MDI) and psychomotor development index (PDI) at 3, 6, 9, and 12 months of age.

RESULTSThe respiratory rate and heart rate decreased in the drug intervention group after fentanyl treatment compared with the control group (P<0.05), and the PIPP scores in the drug intervention group was significantly lower than in the control group (P<0.05). The results of follow-up visits showed no significant differences in MDI and PDI at 3, 6, 9 and 12 months of age between the drug intervention and control groups (P>0.05).

CONCLUSIONSFentanyl can relieve the pain response in neonates receiving mechanical ventilation, with no long-term adverse effects on neurodevelopment.

Analgesics, Opioid ; pharmacology ; Child Development ; drug effects ; Female ; Fentanyl ; pharmacology ; Heart Rate ; drug effects ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Respiration ; drug effects ; Respiration, Artificial