A Case of Acute Cholangitis Due to Opioid-induced Dysfunction of Sphincter of Oddi in the Patient with Breast Cancer

Opioids are known to cause dysfunction of the sphincter of Oddi. However, there are no reports on acute cholangitis due to opioid-induced dysfunction of the sphincter of Oddi. A 75-year-old woman with breast cancer, who had been prescribed oxycodone for lower abdominal pain due to unknown causes for 8 years, suddenly developed hypochondriac pain. We diagnosed the patient as having acute cholangitis and performed endoscopic retrograde pancreatography and technetium hepatobiliary iminodiacetic acid scan. The cause of acute cholangitis was considered to be opioid-induced dysfunction of the sphincter of Oddi. Six and nine days after admission, endoscopic sphincterotomy was performed, after which her upper abdominal pain resolved. Opioids increase biliary pressure and delay bile flow into the duodenum in patients after cholecystectomy. However, the actual clinical outcomes of using opioids for acute cholangitis and pancreatitis remain unknown. Thus, although opioid-induced dysfunction of the sphincter of Oddi is uncommon, it should be assessed in patients who are prescribed opioids.

Observation on therapeutic effect and mechanism research of acupuncture on headache in the recovery phase of ischemic stroke / 中国针灸

OBJECTIVE@#To explore the clinical therapeutic effect and mechanism of acupuncture on headache in the recovery phase of ischemic stroke.@*METHODS@#A total of 97 patients with headache in the recovery phase of ischemic stroke were randomized into an acupuncture group (57 cases) and a western medication group (40 cases). In the western medication group, flunarizine hydrochloride capsule was taken orally 5 mg each time, once a day. In the acupuncture group, acupuncture was applied at Qiuxu (GB 40), Zulinqi (GB 41), Xuanli (GB 6), Shuaigu (GB 8), Fengchi (GB 20) and Baihui (GV 20) for migraine; Chongyang (ST 42), Neiting (ST 44), Jiexi (ST 41), Zusanli (ST 36), Hegu (LI 4), Cuanzhu (BL 2) and Baihui (GV 20) for forehead pain; Jinggu (BL 64), Kunlun (BL 60), Tianzhu (BL 10), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for occipital headache; Taichong (LR 3), Yongquan (KI 1), Sanyinjiao (SP 6), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for parietal headache. The needles were retained for 30 min each time, once a day and 5 times a week. Both of the two groups were given consecutive treatment for 14 days. The visual analogue scale (VAS) and the headache scores before and after treatment and the recurrence rate 1 month after treatment were observed to evaluate the therapeutic effect, before and after treatment, the contents of substance P (SP), dopamine (DA), serotonin (5-HT), alpha-endorphin (α-EP) and beta-endorphin (β-EP) in plasma were determined by ELISA in the two groups.@*RESULTS@#Compared before treatment, the VAS scores, the headache scores and the contents of SP, DA and 5-HT in plasma were reduced and the contents ofα-EP andβ-EP in plasma were increased in the two groups (all <0.01). After treatment, the changes of the VAS score, the headache score and the contents of pain-related factors and endogenous opioid peptides in plasma in the acupuncture group were larger than the western medication group (all <0.05). The total effective rate in the acupuncture group was 84.2% (48/57), which was superior to 62.5% (25/40) in the western medication group, and the recurrence rate in the acupuncture group was lower than the western medication group (both <0.01).@*CONCLUSION@#The therapeutic effect of acupuncture on headache in the recovery phase of ischemic stroke is superior to flunarizine hydrochloride capsule, and the mechanism may relate to down-regulate the pain-related factors and up-regulate endogenous opioid peptides in plasma.

La melatonina induce la síntesis y liberación de las encefalinas en el cerebro de la rata / Melatonin induces enkephalins synthesis and release in the rat brain

Since enkephalins discovery in 1975, several opioid peptides have been included in neuroscience research. Enkephalins have been involved in the homeostasis maintenance of the organism, mostly with cellular and molecular mechanisms implicated in antinociception and narcotic responses. Moreover, enkephalins have been shown to be involved in the control of stress, regulation of cardiovascular functions, modulating primary immune responses, in addition to cellular differentiation processes. As opioid peptides appear to modulate several bioactivities and physiological responses in organisms, this posits that several modifications should occur during their synthesis, cell release, and receptor binding in target cells. At present, it has been demonstrated that the endogenous opioid system (EOS), displays a circadian rhythm, in which its tissue content, presynaptic release, and receptor's number reaches its maximal concentration during the dark phase (24:00h) and the minimal during the early morning (05:00 h). Recently, our group reported that functional pinealectomy disrupts the enkephalin circadian rhythm and significantly reduces the tissue content of opioid peptides in the rat brain. However, the effect was shown to be specific to the hour along the 24h daytime. There were no significant changes during the light period, only during the dark period (01:00h), when the enkephalin tissue content decreased in the experimental group. The effect was reverted when pinealectomized rats were injected with single doses of melatonin (MEL) (150µg/kg i.p.). If the lack of melatonin in the rat brain significantly reduced the enkephalin tissue content, and its exogenous administration re-established the enkephalin tissue levels, it is possible that the hormone is involved in the enkephalin synthesis. In this paper we provide further evidence that supports the relation between melatonin and opioid peptides synthesis and release. In addition, we studied the effect of darkness and melatonin administration in enkephalin tissue levels. Finally, we analyzed the luzindole effect as a melatonin receptor antagonist in the pinealectomized rat brain. Material and methods Subjects: Male Wistar rats were housed in a light and temperature controlled room. Water and pellet food were available ad libitum. This group was subdivided in: 1. Functional pinealectomy group (FP). Rats were housed individually during 15 days in a room with continuous light (<50lux). 2. FP rats were housed in a dark room during four or six hours. 3. FP rats were injected with melatonin (150, 300, 600µg/kg s.c.). 4. FP rats were injected with Luzindole (187.5, 375, 750µg/kg i.p.). After 30 min, the animals were injected with melatonin (150µg/kg). 5. FP rats were injected with melatonin (800µg/ kg) and subjected to the in vitro release processes. The rats were sacrificed by decapitation and the blood collected for melatonin serum determination. The brains were removed and processed for an analytical preparative procedure for the enkephalin determination by radioimmunoassay technique. The in vitro release methodology was performed as follows: tissue samples were homogenized by applying 8 strokes with a Thomas grinder system. The homogenates were centrifuged at 4,000rpm, 4°C during 10 min. Supernatants were recovered and centrifuged at 12,000rpm at 4°C for 20 min. Supernatants were discarded and pellets were resuspended in the homogeneization buffer (1:9 w/v). Samples were placed on top of a Percoll gradient density (23%, 15%, and 10%) and centrifuged at 20,000 rpm at 4°C for 25min. The synaptosomal enriched fraction (15-23%) was obtained and diluted in 1mL of Krebs buffer (mM: NaCl 119, KCl 4.6, CaCl2·2H2O 1.25, KH2PO4 0.85 MgSO4 0.84, NaHCO3 24.8, sucrose 10). Buffer was gasified with a mixture of C0(2) 95% and O2 5%, pH 7.4. 800µL aliquots were placed into plastic chambers. After 20 min of stabilization with Krebs buffer, three different superfusates were collected: 1. basal, 2. potassium [50mM], and 3. post-stimulus (Krebs buffer without potassium). Samples were collected into HCl 0.1N, boiled and subsequently loaded into Amberlite XAD-2 columns (8 × 0.7cm) for solid-phase peptide extraction. The flow rate was held constant at 0.5 mL min-1 and elution of the whole peptide fraction was carried out using a continuous gradient with absolute methanol. Eluted samples were lyophilized and resuspended in 2mL of distilled water and finally stored at -20°C for further quantification of IR-Enkephalin using standard radioimmunoassay procedures. The results showed that functional pinealectomy reduced the opioid tissue content in the different brain structures assayed. The lack of melatonin significantly decreased the enkephalin tissue content when compared to the control group. However, tissue levels of enkephalin material were completely restored after four and six hours of administration of different doses of exogenous melatonin administration to the rats. As continuous light decreases the melatonin content in the brain, darkness should be able to counteract the aforementioned effect. Our results showed that tissue levels of enkephalin material were increased over 200% and 300%, after exposing animals to a four or six-hour period of darkness, when compared to animals exposed to continuous light. Luzindole was used to abolish any melatonin activity via activation of its membrane brain receptors. Our experiments showed that different doses of the antagonist were not able to obliterate the increased content of opioid peptides induced with melatonin administration in the tested brain tissues.

En la actualidad se reconoce que el Sistema Endógeno Opioide (SEO) participa en la regulación y control de la homeostasis; por lo tanto se requiere que los procesos bioquímicos que dan lugar a su síntesis, liberación y unión a receptores se encuentren reguladas de manera endocrina. Diversas líneas de investigación han demostrado que la concentración y liberación presináptica de las encefalinas no permanece constante durante un ciclo de 24 horas. Por el contrario, su síntesis y liberación alcanzan su máxima concentración durante la fase de oscuridad y la mínima durante las primeras horas de la mañana. Recientemente, nuestro grupo de trabajo ha demostrado que la ausencia de melatonina (MEL), por efecto de la pinealectomía funcional, rompe el ritmo circádico y reduce significativamente la concentración de las encefalinas durante la fase de oscuridad. Si la ausencia de la hormona abate la concentración de opioides, es factible que la MEL se encuentre involucrada en la síntesis de las encefalinas. En el presente trabajo se muestran los resultados del efecto de la pinealectomía funcional sobre la concentración tisular y la liberación de los opioides, así como el efecto de la administración exógena de MEL y de su antagonista el luzindol (LZ). Diseño experimental Control Naive. Se utilizaron ratas macho de la cepa Wistar (200-250g), que permanecieron en un cuarto con un ciclo de luz y oscuridad controlada. La fase de luz duró 12 horas y comenzó a las 06:00h. A su vez, este grupo fue subdividido en: 1. Luz Continua (LC): Para abatir la concentración sérica de la hormona, se usó el modelo experimental conocido como pinealectomía funcional. 2. Luz Continua + Oscuridad: La luz abate la concentración de MEL y la exposición a la oscuridad revierte dicho efecto. Un grupo de ratas sometido a la luz continua se colocó en un cuarto con oscuridad durante cuatro y seis horas. 3. Luz continua+melatonina: Para analizar el efecto de la MEL sobre el contenido tisular de opioides, se administró una dosis de MEL (150, 300 y 600µg/Kg s.c.). 4. Luz continua+luzindol (LZ)+MEL: Si la melatonina ejerce su mecanismo de acción al unirse a sus receptores presentes en la membrana plasmática, entonces su efecto podría ser revertido por la presencia del LZ. Por lo tanto, a tres grupos de ratas sometidas a la pinealectomía funcional se les inyectó con LZ a una dosis de 187.5, 375, 750 µg/kg. s.c. Después de transcurridos 30min., los animales fueron inyectados con MEL (150µg/kg. s.c.). 5. Liberación: Se utilizaron tres grupos de ratas: a) control, b) luz continua y c) luz continua+MEL (800µg/kg. s.c.). Post mortem la amígdala fue sometida al proceso preparativo para la obtención de los sinaptosomas. Resultados Los resultados obtenidos en el presente trabajo nos muestran que la pinealectomía funcional reduce significativamente la concentración de encefalinas en todas las estructuras cerebrales analizadas. Sin embargo, el efecto es revertido tanto por la administración exógena de MEL, como por la exposición a la oscuridad. Las diferentes dosis administradas del LZ bloquearon parcialmente el efecto estimulante de la MEL sobre la síntesis de los opioides. Por último, la pinealectomía funcional redujo significativamente la liberación presináptica de encefalinas, misma que se pudo reestablecer con la administración exógena de la hormona. Discusión Las evidencias experimentales del presente trabajo sugieren que la MEL se encuentra relacionada con la síntesis y la liberación de las encefalinas. Por un lado, la pinealectomía funcional redujo significativamente el contenido tisular de encefalinas, pero el efecto fue revertido tanto con la administración exógena de la hormona como con la exposición a la oscuridad. La administración del LZ sólo fue capaz de bloquear parcialmente el efecto estimulante de la MEL sobre la síntesis de encefalinas. El efecto de la MEL sobre la liberación de opioides pone de manifiesto la relación funcional entre ambos sistemas. A menor cantidad de opioides por efecto de la pinealectomía, menor liberación presináptica y por el contrario, una vez administrada la hormona los valores de la síntesis-liberación se restablecen. Conclusión La MEL puede estar involucrada en la síntesis y la liberación de los péptidos opioides.

Effects of orphanin FQ On simple and norepinephrine-activated cardiac function in isolated rat heart / 中华麻醉学杂志

Objective To investigate the effects of orphanin FQ (OFQ) on simple and norepinephrineactivated cardiac function in isolated rat heart.Methods Male SD rats aged 3-4 months weighing 250-280 g were anesthetized with intraperitoneal 25% urethane 1.4-1.8 ml.Their hearts were excised and passively perfused with K-H solutionin a Lanngendorff apparatus.A fluid-filled latex balloon was inserted into left ventricle for measurement of developed pressure.Left ventricular systolic pressure(LVSP),left ventricular end-diastofic pressure(LVEDP),left ventricular developed pressure(LVDP=LVSP-LVEDP),HR and±dp/dtmax were measured.Sixty isolated rat hearts were randomly divided into 10 groups(n=6 each):Ⅰ control group (group C);Ⅱ,Ⅲ,Ⅳ OFQ1,OFQ2,OFQ3 group--OFQ 10-6,10-7,10-8 mol/L were administered via perfusion system respectively;Ⅴ OFQ+UFP group--OFQ 10-6 mol/L+UFP-101 (all OFQ antagonist) 10-6 mol/L were administered;Ⅵ NE group--norepinephrine 10-5 mol/L;Ⅶ,Ⅷ,Ⅸ NE+OFQ groups--NE 10-5 mol/L+OFQ 10-6,10-7,10-8 mol/L were administered respectively;Ⅹ NE+OFQ+UFP group--NE 10-5 mol/L+OFQ 10-6mol/L+UFP-101 10-6mol/L.Results LVSP,LVDP and±dp/dtmax were significantly increased while HR was significantly decreased in the 3 OFQ groups as compared with control group.LVSP,LVDP±dp/dt max and HR were significantly increased in the 3 NE+OFQ groups as compared with NE group.Conclusion OFQ has positive inotropic action and negative chronotropic effect on the isolated rat heart.OFQ Can enhance the positive inotropic and chronotropic effect of NE on the heart.

Molecular mechanisms of opioid peptides in myocardial ischemic preconditioning / 医学研究生学报

Through G protein coupling and intracellular signal transmission, opioid peptides and its receptors in myocardial tissues participate in IPC have the function of early and delayed protection. The molecular mechanism of ”trigger-regulatory medium-effector” is of great significance in the study of the pathogenesis of IPC, as well as exploring the new idea for CHD prevention and cure.

Effects of exogenous brain-derived neurotrophic factors on concentrations of cerebral endogenous opioid peptides in neonatal rats subject to with hypoxic-ischemic brain injury / 中华物理医学与康复杂志

Objective To explore the effects of brain derived neurotrophic factors (BDNF) on concentrations of cerebral endogenous opioid peptides(EOP)in neonatal rats subject to with hypoxic ischemic brain injury (HIBI). Methods Seven day old Sprague Dawley rats were randomly divided into a HIBI+BDNF group (group A),a HIBI group (group B) and a sham operation group (group C). Models of HIBI were established by use of permanent ligation of the left common carotid artery followed by 2.5 hours ofinhalation of 8%O 2+92%N 2, then 0.5 ?g BDNF was injected into the parietal cerebral ventricle in group A immediately. Contents of dynorphin A 1 13 like, ? endorphin like and leu enkaphalin like immunoreactivities (ir DynA 1 13 , ir ? EP and ir LEK) in cortex and hippocampus were measured at 0, 60, 120 min after administration of BDNF. Results The concentrations of ir DynA 1 13 and ir ? EP in the cortex and hippocampus in group B were increased significantly than those in group C at most time points( P

Effects of progesterone on morphine-induced conditioned place preference and levels of endogenous opioid peptides in hypothalamus of rat brain / 中国药理学通报

Aim To investigate the effects of progesterone on morphine rewarding effect and levels of endogenous opioid peptides in hypothalamus of rat brain. Methods Conditioned place preference(CPP)test was used to investigate the morphine rewarding effect, and radioimmunoassay (RIA) was established to deter-mine levels of ?-endorphin(?-EP), leu-enkephalin(L-EK) and dynorphin A(DynA) in hypothalamus of rat brain.Results Compared with NS control group, 5 mg?kg-1 morphine successfully induced the formation of CPP(P

Influence of GnRH Agonist and Neural Antagonists on Stress-blockade of LH and Prolactin Surges Induced by 17 beta-estradiol in Ovariectomized Rats

In our previous study, we demonstrated that immobilization stress blocked estrogen-induced luteinizing hormone(LH) surge possibly by inhibiting the synthesis and release of gonadotropin-releasing hormone (GnRH) at the hypothalamic level and by blocking estrogen-induced prolactin (PRL) surge by increasing the synthesis of dopamine receptor at the pituitary level in ovariectomized rats. The present study was performed to determine whether immobilization stress affects pituitary LH responsiveness to GnRH, and whether endogenous opioid peptide (EOP) and dopamine systems are involved in blocking LH and PRL surges during immobilization stress. Immobilization stress was found to inhibit basal LH release and to completely abolish LH surge. However, the intravenous application of GnRH agonist completely restored immobilization-blocked LH surge and basal LH release. Treatment with naloxone did not exert any effect on immobilization-blocked LH surge but increased basal LH release during immobilization stress. Pimozide did not affect immobilization-blocked LH surge or basal LH release. Naloxone also decreased immobilization-induced basal PRL release, but had no effect on immobilization-blocked PRL surge. Immobilization-increased basal PRL levels were augmented by pimozide treatment and immobilization-blocked PRL surge was dramatically restored by pimozide. We conclude that immobilization stress does not impair pituitary LH response to GnRH, and that the immobilization stress-induced blockage of LH surge is probably not mediated by either the opioidergic or the dopaminergic system. However, immobilization-blockade of PRL surge may be partly mediated by the dopaminergic system.

Effects of low-dose naloxone on morphine analgesia and plasma leveb of opiold peptldes / 中华麻醉学杂志

Objective Low-dose naloxone has been shown to reduce side-effects of morphine while morphine analgesia is not antagonized and may even be enhanced. The purpose of this study was to evaluate the effects of low-dose naloxone infusion (50 ng? kg-1? h-1 ) on morphine analgesia and plasma levels of opioid peptides in patients after abdominal hysterectomy.Methods Forty-two ASA Ⅰ- Ⅱ patients aged 36-50 yrs, weighing 55-67 kg undergoing abdominal hysterectomy under combined spinal-epidural anesthesia were enrolled in this study. Spinal puncture was performed at L2-3 interspace. The patients received intrathecal 0.75% ropivacaine 2.0-2.6 ml. 2% lidocaine was used for epidural injection. The block height was maintained at T8-6 . For postoperative analgesia the patients were randomized to receive either intravenous morphine infusion at 10 ?g?kg-1 ?h-1 (group M, n = 21) or IV morphine infusion (10 ?g?kg-1?h-1)+ naloxone infusion at 50 ng?kg-1?h-1 (group MN, n = 21). Pain was assessed using VAS (0-10) with 0 representing no pain and 10 representing the worst possible pain. Blood samples were taken from peripheral vein before anesthesia (T0), at the end of surgery (T1) and at 6, 24, 48 h (T2,3,4) after operation for determination of plasma levels of ?-endorphin (?-EP), dynorphin A1-13 (Dyn) and leu-enkepholin (L-EK) .Results The patients were comparable with respect to, age, weight, occupation and duration of operation between the two groups. Two patients (1 patient in each group) were excluded from the study because of their refusal to have repeated blood samples taken. The analgesia was significantly better in group MN than that in group M in terms of VAS scores. Plasma level of ?-EP was significantly lower at 6 h after operation (T2 ) but significantly higher at 24 h postop. (T3 ) in group MN compared with that in group M ( P

Study on the Application of Naloxone Hydrochloride in the Treatment of Acute Craniocerebral Trauma / 中国药房

OBJECTIVE:To assess the application value of large dose of naloxone hydrochloride in treating early stage craniocerebral trauma.METHODS:79craniocerebral trauma cases whose GCS scores were5to8scores were enrolled:38(control group)were randomly assigned to receive conventional therapy(dehydrating agent,glucocorticoid,antibacterials,nu?tritional brain cells,and so on),and41(naloxone group)to receive additional naloxone besides the conventional therapy as stated in the control group.Variations on GCS scores,serum?-endorphin(?-EP)level,indexes of respiration and circulation,and safe consciousness time of the2groups after treatment were observed.RESULTS:As compared with the control group,naloxone group had shorter safe consciousness time,lower incidences of respiration failure and circulatory failure,more and faster decrease of serum?-EP level(P

Effects of postnatal treatment with naloxone on plasma gonadotropin prolactin, testosterone and testicular functions in male rats.

Opioid peptides are implicated in the control of gonadotropin and prolactin secretion. The role of opioid antagonist naloxone and its effects on plasma gonadotropin, prolactin, testosterone levels and testicular hyaluronidase, acid phosphatase, [3H]uridine and thymidine incorporation, RNA, DNA and protein concentrations were evaluated in rats after administration of naloxone beginning day 1 through 21 and autopsied on 45, 60 and 90 days of age. Plasma gonadotropin and testosterone levels were significantly elevated after naloxone treatment. Testicular hyaluronidase and acid phosphatase activity increased till 60 days post treatment and declined thereafter. Concentrations of RNA and protein did not change significantly but the concentration of DNA declined at 45 and 60 days of age. These results suggest that endogenous opioid peptides exert regulatory influence on gonadotropin secretion which in turn control the testicular function in the male rat.

PRESSOR EFFECT OF NALOXONE IN ACUTE EXPERI-MENTAL RABBITS / 中国药理学通报

Experiments were carried out on the anesthetized, operated and paralyzed rabbits to study if endogenous opioids are involved in the cardiovascular activity in the acute experimental conditions under which many experiments of pharmacology & physiology were performed. In 6 rabbits, low dose naloxone (0.4 mg/kg, i.v. ) caused sevral temporary pressor waves in 2.9?1.1 min after the injection & apperance of the arrhythmias in 2 animals. In other 9 rabbits, high dose naloxone ( 5 mg/kg, i.v.) raised basal blood pressure in 13.9?7.4 min after the injection, and caused arrhythmias in 5 animals. When the pressor effect was the highest, monoamine metabolites did not change significantly in CSF sampled from the terminal of midbrain aquaduct. Our other experiment has showed that NA & MHPG of the CSF increased during the central stimulation-induced pressor effect. Thus, it is supposed that endogenous opioids play an inhibitory effect on the cardiovascular system in the conditions like present experiment, and the peripheral opioid receptors which are poorly sensitive to naloxone may be involved in the effect.

New achievement in the studies of opioid participation in the regulation of cardiovascular system / 中国药理学通报

The recent research of opioid receptors has achieved great progress, especially in the field of the protection of cardiac muscles in ischemic preconditioning, which makes people pay more attention to the relation ship between opioid receptors and cardiovascular system. This article summarizes the studies of opioid receptors, the measures they take to modulate cardiovascular system and the way they participate in ischemic proconditioning both at home and abroad.