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M M Puig

Publications and source records attributed to M M Puig.

At least 37 records · Page 2Linked to original sources
PubMed1998

Peripheral effects of opioids in a model of chronic intestinal inflammation in mice.

The study describes a model of chronic intestinal inflammation in mice. Inflammation was induced by the administration of one dose of croton oil (CO) (acute CO) or two doses (chronic CO) of intragastric CO, whereas controls received saline (SS); GI transit was measured with charcoal. Chronic CO induced intestinal inflammation substantiated by optical microscopy, weight loss (20%) and a 25% increase in GI transit. The ED50 values in SS animals were 1.67 +/- 0.13 mg/kg for morphine and 0.038 +/- 0.006 mg/kg for fentanyl; chronic CO significantly decreased the ED50 values to 0.16 +/- 0.03 mg/kg (morphine) and 0.006 +/- 0.0005 mg/kg (fentanyl). Thus the potency of morphine increased 10.4 times and that of fentanyl 6.3 times. The effects of enkephalin, but not those of U-50488H, were also significantly enhanced during chronic CO. The antitransit effects of p.o. loperamide increased 11.7 times during chronic CO. All effects were reversed by specific antagonists. The fraction of the active opioid receptor that mediates the antitransit effects of morphine was evaluated using beta-funaltrexamine. In chronic CO, the doses of beta-funaltrexamine needed to antagonize 1 mg/kg of morphine were significantly higher than in SS and acute CO, and the ED50/KA ratio was 20 times lower. These results suggest an increase in the active concentration of mu-opioid receptors during chronic inflammation.

Animals↗
PubMed1997

Ondansetron facilitates neuromuscular transmission in the guinea-pig ileum.

The effects of ondansetron on the neuromuscular function of the guinea-pig ileum were investigated in vitro. Ondansetron, but not tropisetron or MDL 72222 (1alpha-H-3alpha-5alpha-H-tropan-3-yl-3,5-dichlo robenzoate), enhanced submaximal electrically induced contractions (EC50) = 1.3 x 10(-5) M). Desensitization with 5-hydroxytryptamine (1 x 10(-5) M) or 2-methyl-5-HT (1 x 10(-5) M) abolished this facilitatory response, which remained unaltered after desensitization with 5-methoxytryptamine (1 x 10(-5) M) or addition of tropisetron, MDL 72222, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan, SB203186 (1-piperidinylethyl-1H-indole-3 carboxylate hydrochloride), pirenzepine or hexamethonium. At higher concentrations, ondansetron decreased the electrically induced contractions (EC50 = 1 x 10(-4) M); the inhibitory response was unaffected by (-)-naloxone (1 x 10(-6) M) or idazoxan (1 x 10(-6) M). We conclude that, in the guinea-pig ileum, ondansetron elicits a biphasic response: facilitation of neuromuscular transmission mediated by a serotonergic receptor distinct from the 5-HT3, 5-HT4 or putative 5-HT1P receptors, and an inhibitory response that does not involve opiate or alpha2-adrenoceptors.

5-Methoxytryptamine↗
PubMed1997

Reversal of tolerance to the antitransit effects of morphine during acute intestinal inflammation in mice.

1. The aim of investigation was to establish and compare the reversibility of tolerance to the antitransit effects of morphine by three different procedures: (a) acute inflammation of the gut, (b) lorglumide a cholecystokininA (CCKA) receptor antagonist, or (c) MK-801, an N-methyl-D-aspartate (NMDA) receptor ion channel blocker. The type of interaction between morphine and lorglumide or MK-801 on the inhibition of gastrointestinal transit (GIT) in naive animals was also evaluated. 2. Male Swiss CD-1 mice were implanted with 75 mg of morphine base or placebo pellets. Gastrointestinal transit was assessed with a charcoal meal and results expressed as % inhibition of GIT. Inflammation was induced by the intragastric (p.o.) administration of croton oil (CO), while controls received castor oil (CA) or saline (SS). Morphine was administered by subcutaneous (s.c.) or intracerebroventricular (i.c.v.) injection, to naive and tolerant animals treated with CO, CA or SS. Dose-response curves for s.c. morphine were also performed in naive and tolerant mice receiving 5.2 or 7.4 nmol (s.c.) lorglumide or MK-801, respectively. 3. The ED50 values for inhibition of GIT by s.c. morphine were: 45.9 +/- 2.7 and 250.1 +/- 3.1 nmol in naive and tolerant animals, respectively, demonstrating a five fold decrease in the potency of morphine. In naive animals, inflammation (CO) decreased the ED50 of morphine three times (14.4 +/- 2.2 nmol). However, no tolerance to s.c. morphine (ED50 16.4 +/- 2.6 nmol) was manifested during intestinal inflammation. After i.c.v. administration, a similar degree of tolerance to morphine was observed (4.8 fold decrease in potency). Intestinal inflammation had no effect on the ED50 values of i.c.v. morphine in naive and tolerant animals, showing that reversal of tolerance is related to local mechanism/s. Mean values for intestinal pH were 6.9 +/- 0.04 and 6.2 +/- 0.04 in SS and CO treated mice, respectively. In addition, morphine was 74 times more potent by the i.c.v. than by the s.c. route (naive-SS). 4. Morphine and lorglumide interacted synergistically in naive animals; in addition, the administration of lorglumide reversed tolerance to s.c. morphine. No interaction (additivity) was observed in naive animals when morphine and MK-801 were administered in combination. However, the drug completely reversed tolerance to the antitransit effects of morphine. 5. The present investigation shows that acute inflammation of the gut reverses tolerance to the antitransit effects of s.c. morphine by a peripheral mechanism. Qualitatively similar results were obtained after the administration of lorglumide or MK-801. Our results suggest that a local decrease in pH could play an important role during inflammation, while antagonism of endogenous compensatory systems would explain the reversal of tolerance induced by lorglumide or MK-801.

Acute Disease↗
PubMed1996

Comparative assessment of the anaesthetic and analgesic effects of intramuscular and epidural clonidine in humans.

PURPOSE: The aim of the study was to assess and compare in analogous controlled experimental conditions, the anaesthetic sparing and analgesic effects of the same dose of clonidine administered by the intramuscular (im) and epidural (ep) routes. METHODS: We used a randomized, double blind and placebo controlled protocol. Sixty patients undergoing abdominal hysterectomy were distributed into three groups who, 30 min before surgical incision, received: 300 micrograms ep clonidine plus im saline; ep saline plus 300 micrograms im clonidine; or ep and im saline (ss). General anaesthesia was maintained with 60% N2O in O2, and isoflurane administered at concentrations to maintain mean arterial pressure (MAP) and heart rate (HR) within 20% of basal values. Isoflurane requirements (mass spectrometry), cardiovascular variables (MAP, HR), and plasma concentrations of glucose, cortisol and prolactin were evaluated at critical time points. In the recovery room (RR), sedation (Ramsay) and pain intensity (VAS) were estimated at the time of analgesia request (TAR). RESULTS: Intramuscular and ep clonidine decreased isoflurane requirements similarly by about 85% (P < 0.001). Patients in the ep group had lower MAP (P < 0.03) and HR (P < 0.001) than in the im group, but im and ep clonidine similarly blunted the plasma prolactin increase induced by intubation. In RR, ep but not im clonidine (P < 0.01) induced postoperative analgesia demonstrated by a prolonged TAR 80.8 +/- 7.3 (ep) 35.9 +/- 3.2 (im) and 44.5 +/- 5.1 (ss) min and a lower VAS (P < 0.05). CONCLUSIONS: Epidural and intramuscular clonidine decreased isoflurane requirements similarly, but only the epidural route provided postoperative analgesia, suggesting a spinal site for the analgesic action.

Adult↗
PubMed1996

Spinal anesthesia with bupivacaine and fentanyl in geriatric patients.

We assessed the risks and benefits of the administration of fentanyl during spinal anesthesia in the elderly. Forty patients (70-83 yr) undergoing knee or hip replacement were studied. Preoperatively, cognitive function (minimental state examination [MMSE]), associated pathology, medications, and treatment were evaluated. Patients had spinal anesthesia with 12.5 mg bupivacaine plus saline (SS; n = 21) or 25 micrograms fentanyl (FN; n = 19). The number of ailments and drugs per patient were 2.5 and 2.3, respectively; 35%-44% of disorders were untreated, 16%-26% were symptomatic, and 33% were adequately treated. Groups were comparable regarding demographic data and characteristics of the spinal block. Group FN had more pruritus (P < 0.02) and lower SaO2 (P < 0.007), but prevalence of side effects was similar. Pain intensity (visual analog scale [VAS], facial expression test [FET] at the time of analgesia request (TAR) was lower in Group FN (P < 0.01). A poor correlation between VAS and FET (range 0.42-0.58) was obtained. MMSE at hospital discharge was no different from preoperative values. Our results show that 25 micrograms of spinal fentanyl do not modify spinal anesthesia in the elderly, but induces pruritus and O2 desaturation. The decrease in postoperative pain intensity and the preservation of cognitive function would justify the use of spinal fentanyl in the elderly.

Aged↗
PubMed1996

Interaction of morphine and clonidine on gastrointestinal transit in mice.

BACKGROUND: Combinations of drugs are frequently used to achieve effective analgesia while minimizing side effects. Although the analgesic effects of morphine and clonidine seem to be synergistic, few studies have investigated other effects. Their role in inhibiting gastrointestinal transit was evaluated using different methods of analysis. METHODS: Percentage inhibition of transit induced by morphine, clonidine, or their combination was measured in mice that had been given an intragastric charcoal meal. Dose-response curves were obtained for each drug individually; for morphine:clonidine at 1:3, 1:1, and 1:0.33 ratios; and for morphine in the presence of 0.0138 mg/kg clonidine. The interaction was evaluated by isobolograms, combination indexes, and fixed-dose analysis. RESULTS: Each drug and their combinations inhibited transit in a dose-related manner. Combinations of morphine and clonidine produced interaction that depended on the ratio and level of response. The interaction analyzed by isobolograms and combination indexes showed that combinations in 1:1 and 1:3 proportions were synergistic at the median effective doses or less and were antagonistic at larger doses. Fixed-dose analysis using different ratios showed similar results. The effects of the combination (median effective dose at 1:1 ratio) were antagonized by efaroxan but not by naloxone, suggesting a predominant role of alpha-2-mediated effects. CONCLUSIONS: Investigations into drug interactions should include several levels of response and combinations at different ratios. Isobolographic analysis permits the statistical evaluation of results without making assumptions about mechanisms of action of the drugs or their interactions. In this study, the combination of morphine and clonidine should produce synergy, antagonism, or no interaction depending on the relative doses and the level of effect.

Adrenergic alpha-Antagonists↗
PubMed1996

Effects of subarachnoid lidocaine, meperidine and fentanyl on somatosensory and motor evoked responses in awake humans.

Although the effects of local anaesthetics (LA) on motor and sensory transmission in the spinal cord have been described, the effects of opioids are controversial. Our aim was to evaluate the action of clinically relevant doses of subarachnoid (SA) meperidine (MP) and fentanyl (FN), on somatosensory (SSEP) and cortical motor evoked responses (CMER) in awake subjects. Thirty ASA I-II patients scheduled for infra umbilical surgery received SA (N = 10/group): 1 mg/kg lidocaine (LD), 1 mg/kg MP or 25 mu g FN. SSEP elicited by stimulation of the posterior tibial nerve at the ankle, and cortical motor evoked response at rest (r-CMER) and during facilitation (f-CMER) were obtained prior and 30 min after treatment. Conduction at the proximal segment of the motor nerve (F-wave) was evaluated by stimulation of the posterior tibial nerve at the popliteal fossa. Motor/sensory block and side effects were clinically assessed. LD completely abolished SSEP and CMER. At the same dose, MP abolished SSEP in 40% of the patients, while r-CMER and f-CMER were absent in 70% and 30%, respectively; in addition, the F-wave was absent in 50% of the patients. Fentanyl induced small changes in the latencies of SSEP and F-wave; however, a 28% decrease in the amplitude of the f-CMER (P<0.05) was observed. Pruritus was present in 60% of patients in the FN group (P<0.006). Our results show that while LD and MP block sensory and motor conduction at the spinal roots, FN seems to decrease the excitability of the spinal interneurons in the corticospinal tract.

Adult↗
PubMed1996

The inhibitory effects of alpha(2)-adrenoceptor agonists on gastrointestinal transit during croton oil-induced intestinal inflammation.

1. The peripheral effects of alpha(2)-adrenoceptor agonists were investigated in a model of intestinal inflammation induced by intragastric administration of croton oil (CO). Our hypothesis was that inflammation would 'sensitize' adrenoceptors in peripheral and/or central terminals of myenteric and submucous plexus neurones, and enhance systemic effects of alpha(2)-adrenoceptor agonists. 2. Male swiss CD-1 mice, received intragastrically CO (0.05 ml), castor oil (CA, 0.1 ml) or saline (SS) 3 h before the study: gastrointestinal transit (GIT) was evaluated 20 min afterwards with a charcoal meal. The presence of inflammation was assessed by electron microscopy. 3. The intragastric administration of CA or CO caused an increase in GIT and weight loss, but only CO induced an inflammatory response. Both clonidine (imidazoline1/alpha(2)-agonist) and UK-14304 (alpha(2)-agonist) produced dose-related inhibitions of GIT in all groups. During inflammatory diarrhoea (CO), potencies of systemic (s.c.) clonidine and UK-14304 were significantly increased 3.5 and 2.1 times, respectively, while potencies remained unaltered in the presence of diarrhoea without inflammation (CA). The effects were reversed by administration (s.c.) of receptor-specific adrenoceptor antagonists, but not by naloxone. 4. Clonidine was 8.3 (SS) and 2.8 (CO) times more potent when administered intracerebroventricularly (i.c.v.), than when administered s.c. Inflammation of the gut did not alter the potency of i.c.v. clonidine, demonstrating that enhanced effects of s.c. clonidine are mediated by peripheral receptors. During inflammation, i.c.v. efaroxan did not antagonize low doses of s.c. clonidine (ED20 and ED50S), but partially reversed ED80S, further supporting the peripheral effects of the agonists in CO treated animals. 5. The results demonstrate that inflammation of the gut enhances the potency of alpha(2)-adrenoceptor agonists by a peripheral mechanism. The results also suggest that the inflammatory response induces an up-regulation or sensitization of alpha(2)-adrenoceptors and/or imidazoline receptors.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1996

Effects of morphine and liposomal morphine in a model of intestinal inflammation in mice.

We have investigated the antitransit effects of free and liposomal morphine in a model of intestinal inflammation. Mice received saline or croton oil orally, 3 h prior to evaluation, and gastrointestinal transit was measured 20 min afterwards. Peak/duration of effects, potency (ED50) and antagonism by naloxone and naloxone methiodide were evaluated. Peak effects occurred 30 and 40 min after administration of morphine and liposomal morphine, respectively. Encapsulated morphine had a more pronounced and prolonged effect than morphine. Comparison of the ED50S demonstrated that the potency of liposomal morphine was 3.5 times higher than that of morphine during inflammation; in addition, inflammation increased the potency of morphine and liposomal morphine, 3 and 9.2 times, respectively. The effects of morphine and liposomal morphine in croton oil-treated mice were reversed by naloxone and naloxone methiodide. The results show that during inflammation, the potency and duration of the antitransit effects of morphine are significantly enhanced by encapsulation.

Animals↗
PubMed1996

Peripheral effects of opioids in a model of intestinal inflammation in mice.

The study evaluates the peripheral component of the antitransit effects of opioids during acute intestinal inflammation induced by the intragastric administration of croton oil (CO) in mice. Gastrointestinal transit was measured 3 h after CO or saline (SS) administration with a charcoal meal. In both groups, the effects of mixed (morphine, fentanyl, U-50488H) and peripherally acting (N-methylmorphine, PL017, ICI-204448) opioids and their antagonism by naloxone and naloxone methiodide were established. During inflammation, the potencies of morphine and N-methylmorphine increased 3 times, and those of fentanyl and PL017, 1.9 times. The effects were reversed by naloxone (0.1 mg/kg) and naloxone methiodide (0.3 mg/kg). No dose-response relationships could be elicited with U-50488H or ICI-204448, and their antitransit effects were analogous in SS- and CO-treated animals. These results show that during inflammation the enhanced antitransit effects of opioids are primarily mediated by interaction with opioid receptors located at peripheral sites. In addition, inflammation of the gut seems to induce a sensitization of mu-but not kappa-opioid receptors.

Animals↗
PubMed1996

Respiratory and analgesic effects of meperidine and tramadol in patients undergoing orthopedic surgery.

The respiratory and analgesic effects of i.v. meperidine, tramadol and their correlation with plasma concentrations of meperidine, tramadol and O-demethyltramadol were determined. Forty-eight patients after total hip or knee replacement were randomly distributed into 3 groups (n = 16 each). At the time of analgesia request, they received in a double-blind manner, i.v. single doses of 100 mg meperidine, 100 mg tramadol, or saline. Thirty minutes after treatment, patients who requested additional analgesia were rescued with 75 mg diclofenac and morphine as required. Patients were evaluated at the time of analgesia request and at set intervals during 4 h. Meperidine induced sedation (p < 0.05), respiratory depression (tidal volume, p < 0.047; respiratory rate, p < 0.004; % O2 Sat, p < 0.036), and hypercapnia (PaCO2, p < 0.002). Incidence of nausea and vomiting was higher with tramadol (p < 0.02). For the first 30 min, meperidine produced lower pain intensity scores than tramadol or saline (p < 0.05). At this time, 14/16 patients on saline, 8/16 on meperidine and 11/16 on tramadol were rescued. Onset for meperidine analgesia was 10 min and > 30 min for tramadol. Both opioids produced similar degree of analgesia in patients who were not rescued. A negative correlation (r = -0.99) between analgesia and tramadol concentrations and a poor positive correlation (r = +0.54) with O-demethyltramadol (a metabolite of tramadol) was observed. Pain intensity differences correlated negatively with meperidine plasma concentrations during the first 30 min (r = -0.97) and positively thereafter (r = +0.92). In the present study, meperidine and tramadol produced comparable analgesia, with a different time course profile, but meperidine induced sedation and respiratory depression while tramadol did not.

Aged↗
PubMed1995

Pharmacological evidence for the involvement of the endogenous opioid system in the response to local inflammation in the rat paw.

We have investigated the role of the endogenous opioid system (EOS) on the inflammatory response induced by subplantar (s.p.) injection of saline (SS) and carrageenan (CA) in the hindpaw of the rat. The administration of intraperitoneal (i.p.) naloxone was used in order to unmask the effects of endogenous opiates released during peripheral inflammation. Three groups of rats received one of the following s.p. treatments: SS, CA, or no injection (NI). Pain pressure threshold (PPT), paw volume (edema) and local temperature were evaluated in baseline conditions and 3 h after treatment. In each group, the effects of i.p. vehicle, naloxone and (+)-naloxone (0.1 mg/kg) were also investigated. Both SS and CA induced a significant inflammatory response with hyperalgesia, edema and local hyperthermia. The i.p. administration of naloxone but not that of (+)-naloxone 15 min prior to testing, significantly increased edema in all groups of treatment (P < 0.05), without altering PPT or local temperature. Two-way ANOVA revealed that treatment and drugs, as well as their interaction, had a significant impact on edema which was related to the effects of CA and naloxone. Our findings illustrate the involvement of the EOS in the physiological response to local injury, regulating microvascular leakage in the inflamed tissues.

Animals↗
PubMed1995

Effects of interpleural bupivacaine on respiratory muscle strength and pulmonary function.

BACKGROUND: Several reports suggest that interpleural local anesthetics may have deleterious effects on respiratory function. The current study investigated the effects of interpleural bupivacaine on human respiratory muscles and lung function. METHODS: Thirteen patients (55 +/- 4 yr old) with normal respiratory function and scheduled for cholecystectomy entered the study before surgery. Respiratory parameters were compared before and after the interpleural administration of 20 ml 0.5% bupivacaine plus 1:200,000 epinephrine while patients were supine; we evaluated breathing pattern, dynamic and static lung volumes, airway conductance, maximal inspiratory pressures (at the mouth; at the esophagus [Pessniff]; at the abdomen [Pgasniff]; and transdiaphragmatic [Pdisniff]), functional reserve (tension-time index) of the diaphragm, and maximal expiratory pressures (at the mouth; at the esophagus [Pescough]; and at the abdomen [Pgacough]). Hemoglobin oxygen saturation by pulse oximetry, heart rate, and mean arterial pressure were continuously monitored. RESULTS: Respiratory rate (15 +/- 1 to 19 +/- 1 breaths/min; P < 0.01) and heart rate (78 +/- 3 to 83 +/- 3 beats/min; P < 0.01) were slightly increased. Dynamic and static lung volumes, airway conductance, hemoglobin saturation, and the remaining breathing pattern parameters were unchanged. Regarding respiratory muscles, maximal inspiratory pressure at the mouth, Pessniff, and tension-time index of the diaphragm did not change. Pdisniff decreased slightly (102 +/- 10 to 92 +/- 10 cmH2O; P < 0.05) because of a change in Pgasniff (24.2 +/- 7.4 to 18.4 +/- 6.8 cmH2O; P < 0.05). Maximal expiratory pressure at the mouth remained unaltered, but Pgacough decreased (108 +/- 10 to 92 +/- 8 cmH2O; P < 0.01), and Pescough showed a trend to decrease (92 +/- 13 to 78 +/- 10 cmH2O; P = 0.074). CONCLUSIONS: In our experimental conditions, interpleural bupivacaine did not significantly change lung function or inspiratory muscle strength but induced a slight decrease in abdominal muscle strength. Although this effect was minimal, its clinical relevance needs to be evaluated further in patients with impaired respiratory function.

Adult↗
PubMed1995

Peripheral effects of naloxone in mice with acute diarrhea associated with intestinal inflammation.

The aim of the study was to evaluate the effects of centrally and peripherally acting opioid antagonists such as naloxone (NX), naloxone methiodide, (+)-naloxone [(+)NX], (-)-a-5,9-diethyl-2'-hydroxy-2 (3-furylmethyl)-6,7-benzomorphan and naltrindole on gastrointestinal (GI) transit in mice with diarrhea associated with intestinal inflammation. Our hypothesis was that diarrhea/inflammation could induce a release of endogenous opioid peptides that would play an inhibitory role in the physiological response to intestinal inflammation; the administration of opioid antagonists would uncover the effects of the endogenous opioid peptides on the gut. Diarrhea associated with inflammation was induced in mice by administration of croton oil (CO) although control animals received saline (SS); GI transit was evaluated with a charcoal meal. The i.p. administration of 0.1 mg/kg NX or NXME, induced a significant increase in GI transit in CO but not in SS-treated animals (P < .005). At the same dose, (+)NX had no effect either in CO or SS groups. The kappa antagonist MR-2266 (1 and 3 mg/kg) had no effect on GI transit in SS or CO animals. However, the delta antagonist naltrindole (3 mg/kg), caused a small but significant (P < .01) increase in GI transit in the CO group. These results suggest that endogenous opioid peptides are released in CO-treated animals and exert an inhibitory control of intestinal motility, which is unmasked by opioid antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

The effect of clonidine on intra-operative requirements of fentanyl during combined epidural/general anaesthesia.

The study evaluates the analgesic effects of epidural clonidine in patients undergoing abdominal hysterectomy under combined epidural/general anaesthesia. Forty ASA 1-2 patients were divided into two groups who received epidurally either clonidine 300 micrograms (group 1) or placebo (group 2). Anaesthesia was maintained with oxygen/nitrous oxide, a midazolam infusion, vecuronium, and boluses of fentanyl 100 micrograms administered as needed to maintain cardiovascular stability. The mean (SD) intraoperative fentanyl requirements were 2.05 (0.18) and 3.66 (0.3) micrograms.kg-1.h-1 for groups 1 and 2 respectively (p < 0.001). Patients in Group 1 had a lower heart rate after tracheal intubation and surgical incision (p < 0.02). In the recovery room, pain intensity was lower in group 1 (p < 0.003) and the mean (SD) time until analgesia request was increased from 48.5 (8.4) min in group 2 to 235.7 (33.2) min in group 1 (p < 0.001). Our results demonstrate that epidural clonidine produces decreased fentanyl requirements, improved cardiovascular stability, reduced pain intensity and effective postoperative analgesia in the recovery room.

Adult↗
PubMed1994

Diarrhea associated with intestinal inflammation increases the potency of mu and delta opioids on the inhibition of gastrointestinal transit in mice.

The aim of the study was to determine the effects of intestinal inflammation induced by croton oil on the antitransit action of systemically administered receptor-specific opioids. Our hypothesis was that inflammation would "sensitize" opioid receptors in peripheral and/or central terminals of myenteric and submucous plexus neurons and enhance the effects of exogenously administered opioids. Diarrhea was induced by p.o. administration of croton oil and was demonstrated by weight loss and increased gastrointestinal transit. Histologically, an increased number of clear vesicles in the cytoplasm of jejunal epithelial cells and enlarged spaces filled with fine granular material in the extravascular compartment were observed. Subcutaneous morphine and fentanyl produced dose-related inhibitions of gastrointestinal transit in saline-treated controls with ED50 values of 1.24 +/- 0.06 and 0.036 +/- 0.010 mg/kg, respectively. In animals with diarrhea, dose-response curves were parallel and shifted to the left with a significant decrease in ED50 values of 2.95 times for morphine and 1.89 for fentanyl. The effects of the delta agonist Tyr-D-Pen-Gly-Phe-D-Pen, but those of U50,488H [trans-3,4-dichloro-N-methyl-N-(2-(1-pyrrolydynil)cyclohexyl) benzeneazetamine] also were increased significantly during diarrhea associated with inflammation. Naloxone (0.1 mg/kg), MR-2266 [(-)-a-5,9-diethyl-2'-hydroxy-2-(3-furylmethyl)-6,7-benzomorphan] (3 mg/kg) and naltrindole (1 mg/kg) antagonized the effects of the receptor-specific opioid agonists used in the study. Our results show that the potency of s.c. mu and delta opioids is increased during inflammation of the gut and that the effect is mediated by the same type of opioid receptors present in the noninflamed tissue. These results support the view that a sensitization of opioid receptors occurs during acute inflammation of the gut.

Amino Acid Sequence↗
PubMed1993

Simultaneous changes in hypothalamic catecholamine levels and plasma corticosterone concentration in the rat after acute morphine and during tolerance.

The effects of morphine on plasma corticosterone and hypothalamic noradrenaline (NA) and dopamine (DA) content were studied in naive and in morphine-tolerant rats. Acutely administered morphine (30 mg/kg i.p.) significantly increased the plasma levels of corticosterone and significantly reduced the hypothalamic NA and DA content. In chronically morphine-treated rats (subcutaneously implanted with pellets for 7 days), a challenge dose of morphine (30 mg/kg intraperitoneally (i.p.)) did not modify the plasma corticosterone levels and inhibited the morphine-induced decreases in hypothalamic NA and DA content. These results suggest that: (1) In naive rats, the morphine-induced activation of hypothalamus-pituitary-adrenocortical (HPA) axis is mediated by catecholaminergic neurons in the hypothalamus; (2) In tolerant rats morphine did not modify the plasma corticosterone concentrations, presumably by attenuating hypothalamic noradrenergic and dopaminergic activity. (3) Hypothalamic catecholamines have a role in regulating the HPA axis during morphine tolerance.

Animals↗