naloxone and Abdominal-Pain

Endogenous opioid peptides have been implicated in the regulation of pain perception, behaviour, gastrointestinal activity and other physiological responses. However, the functional role of these peptides in the horse has yet to be elucidated. The opioid antagonist, naloxone, is often administered to infer endogenous opioid effects. In the present study, naloxone (0.75 mg/kg bodyweight) was administered to eight Thoroughbred racehorses and a number of behavioural and autonomic responses were measured. Naloxone produced rapid onset diarrhoea, restlessness, abdominal checking, tachycardia, tachypnoea, paradoxical yawning and diaphoresis. These responses described an acute abdominal distress syndrome similar to spasmodic colic. Results from this study suggest that, in the horse, endogenous opioids: 1) influence behaviour, 2) modify intestinal activity and sensation, and 3) if perturbed, may be involved in pathophysiology of colic.

Topics: Abdominal Pain; Animals; Behavior, Animal; Colic; Defecation; Diarrhea; Gastrointestinal Diseases; Heart Rate; Horse Diseases; Horses; Naloxone; Respiration; Syndrome; Yawning

Use of strong opioids like morphine as analgesics for painful conditions in haematological malignancies is a challenging task. We report a unique case of chronic myelomonocytic leukaemia presenting with opioid toxicity overlapping with tumour lysis syndrome. The patient was on hydroxyurea-based chemotherapy for the primary disease. She was receiving oral morphine for abdominal pain due to splenomegaly. She was brought to the emergency in unresponsive state with pinpoint pupils. Opioid overdose leading to unconsciousness was suspected as the first diagnosis. Further workup revealed a final diagnosis of tumour lysis syndrome overlapping with opioid overdose. The patient was ventilated and started on naloxone infusion, and supportive measures for managing tumour lysis were added. The patient gradually improved and was extubated on the fifth day of ventilation. This case presents several learning points for the treating physician. Haematological malignancies have a dynamic course of disease with waxing and waning tumour burden during the course of chemotherapy. This fact should be kept in mind when prescribing strong opioids like morphine on outpatient basis to these patients. Massive tumour cell lysis during the course of chemotherapy may precipitate tumour lysis syndrome and may lead to renal dysfunction which makes the patient susceptible to morphine-related adverse effects. Pain physician should keep a watch for therapy-related adverse effects to avoid diagnostic and therapeutic dilemma associated with coexisting features of these two fatal conditions.

Topics: Abdominal Pain; Aged; Analgesics, Opioid; Drug Overdose; Female; Humans; Leukemia, Myelomonocytic, Chronic; Morphine; Naloxone; Splenomegaly; Treatment Outcome; Tumor Lysis Syndrome

Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional disorder of the gastrointestinal (GI) tract. The major IBS-D symptoms include diarrhea, abdominal pain and discomfort. High density of opioid receptors (ORs) in the GI tract and their participation in the maintenance of GI homeostasis make ORs ligands an attractive option for developing new anti-IBS-D treatments. The aim of this study was to characterize the effect of methyl-orvinol on the GI motility and secretion and in mouse models mimicking symptoms of IBS-D.. In vitro, the effects of methyl-orvinol on electrical field stimulated smooth muscle contractility and epithelial ion transport were characterized in the mouse colon. In vivo, the following tests were used to determine methyl-orvinol effect on mouse GI motility: colonic bead expulsion, whole GI transit and fecal pellet output. An antinociceptive action of methyl-orvinol was assessed in the mouse model of visceral pain induced by mustard oil.. Methyl-orvinol (10. Methyl-orvinol could become a promising drug candidate in chronic therapy of functional GI diseases such as IBS-D.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Abdominal Pain; Analgesics; Analgesics, Opioid; Animals; Colon; Diarrhea; Disease Models, Animal; Gastrointestinal Motility; Gastrointestinal Transit; Irritable Bowel Syndrome; Male; Mice; Mice, Inbred BALB C; Muscle Contraction; Muscle, Smooth; Naloxone; Naltrexone; Receptors, Opioid; Thebaine

Topics: Abdominal Pain; Analgesics, Opioid; Delayed-Action Preparations; Female; Humans; Middle Aged; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Oxycodone; Portal Vein; Stomach Neoplasms; Substance Withdrawal Syndrome; Treatment Outcome; Venous Thrombosis

Topics: Abdominal Pain; Acetaminophen; Administration, Oral; Adult; Cataract Extraction; Cholecystectomy; Codeine; Contraindications; Drug Combinations; Female; Glaucoma; Humans; Meperidine; Middle Aged; Naloxone; Premedication; Spasm; Sphincter of Oddi; Time Factors

The study examined the antinociceptive potency of dipeptide compound GB-115 (amide N-6-phenylhexanoyl-glycyl-L-tryptophan) during thermal and chemical noxious stimulation of mice. Peroral administration of GB-115 (0.1-20 mg/kg) decreased the incidence of abdominal contractions induced with intraperitoneal acetic acid (0.75%). This effect was comparable to that of sodium diclofenac (20 mg/kg); it was only partially antagonized with naloxone indicating the presence of significant non-opioid component in analgesic effect of GB-115. Ability of this dipeptide to moderate the nociceptive response in tail flick test under a non-selective blockade of the opioid receptors with naloxone and the absence of similar analgesic potency assessed in the hot plate test attest to predominant effect of GB-115 on spinal opioid receptors.

Topics: Abdominal Pain; Acetic Acid; Administration, Oral; Analgesics; Analysis of Variance; Animals; Dipeptides; Hot Temperature; Male; Mice; Naloxone; Pain Measurement; Statistics, Nonparametric; Stimulation, Chemical

Carvacrol (5-isopropyl-2-methylphenol) is a monoterpenic phenol which is present in the essential oil of oregano and thyme. We have investigated the behavioural effects of carvacrol in animal models of pain, such as acetic acid-induced abdominal constriction, formalin and hot-plate tests in mice. The spontaneous motor activity of animals treated with carvacrol was investigated using open-field and rotarod tests.. Carvacrol was administered orally, at single doses of 50 and 100 mg/kg while indometacin (5 mg/kg), morphine (7.5 mg/kg) and diazepam (2 mg/kg) were used as standard drugs. Naloxone (1 mg/kg) and l-arginine (150 mg/kg) were used to elucidate the possible antinociceptive mechanism of carvacrol on acetic acid-induced abdominal constriction and formalin tests.. The results showed that carvacrol produced significant inhibitions on nociception in the acetic acid-induced abdominal constriction, formalin and hot-plate tests. In the open-field and rotarod tests carvacrol did not significantly impair the motor performance. The effect of the highest dose of carvacrol in mice in the acetic acid-induced abdominal constriction and formalin tests were not reversed by naloxone or l-arginine.. Based on these results, it has been suggested that carvacrol presents antinociceptive activity that may not act through the opioid system nor through inhibition of the nitric oxide pathway.

Topics: Abdominal Pain; Acetic Acid; Analgesics; Animals; Arginine; Behavior, Animal; Cymenes; Disease Models, Animal; Formaldehyde; Hot Temperature; Male; Mice; Mice, Inbred Strains; Monoterpenes; Motor Activity; Naloxone; Narcotic Antagonists; Oils, Volatile; Origanum; Pain; Phytotherapy; Plant Extracts; Thymus Plant

Pluchea sagittalis, an herbaceous plant widely distributed in South America, is used in folk medicine for the treatment of digestive diseases and inflammation.. This study was designed to investigate the antinociceptive and gastroprotective effects of the ethanolic extract (EE) of aerial parts from Pluchea sagittalis in rodents.. The antinociceptive effects of EE was evaluated in mice after oral administration in chemical tests (acetic-acid, glutamate and formalin) or by biting behavior following intrathecal administration of cytokines such as interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in mice. Furthermore, rats were treated with EE and subsequently exposed to acute gastric lesions induced by 80% ethanol. Afterwards the gastric lesion extension and the mucus levels of gastric mucosa were measured.. The oral administration of EE showed a dose-dependent inhibition of acetic acid-induced abdominal constrictions and glutamate-induced pain in mice, with ID(50) values of 624.0 (523.0-746.0) mg/kg and 368.0 (216.0-628.0) mg/kg, respectively. In the formalin test, the EE also produced significant inhibition of the inflammatory phase, with an ID(50) value of 411.0 (183.0-721.0) mg/kg; however, it was ineffective in the neurogenic phase caused by formalin. In addition, oral treatment with EE caused a significant inhibition of biting behavior induced by i.t. injection of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). The antinociception caused by the EE (300 mg/kg, p.o.) was not reversed by naloxone (1 mg/kg, i.p.) when assessed in the acetic acid writhing test. The EE (300-1000 mg/kg, p.o.) did not affect the motor coordination of animals in an open-field model. Oral treatment with the EE protected rats against gastric lesions induced by ethanol, with an ID(50) value of 55.0 (46.6-64.9) mg/kg, and increased the mucus levels of gastric mucosa to levels found in the non-lesioned group.. The mechanism by which the extract produced antinociception still remains unclear, but this effect seems to be primarily related to the modulation or inhibition of the action of pro-inflammatory mediators. Furthermore, these data support, at least in part, the ethnomedical use of Pluchea sagittalis.

Topics: Abdominal Pain; Analgesics; Animals; Anti-Inflammatory Agents; Asteraceae; Behavior, Animal; Dose-Response Relationship, Drug; Gastric Mucosa; Gastrointestinal Agents; Inflammation; Male; Mice; Naloxone; Phytotherapy; Plant Components, Aerial; Plant Extracts; Rats; Rats, Wistar; Stomach Diseases

We have investigated the antinociceptive activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith, in acetic acid-induced abdominal writhing test and hot plate test in mice. 1 given by intraperitoneal route produced significant dose-dependent antinociceptive effect in all the test models used. In addition, the antinociceptive effect of 1 in the hot plate test was reversed by the non-selective opioid receptor antagonist naloxone, suggesting that the opioid system is involved in its analgesic mechanism of action.

Topics: Abdominal Pain; Acetic Acid; Analgesics; Animals; Dose-Response Relationship, Drug; Hot Temperature; Male; Mice; Mice, Inbred BALB C; Naloxone; Narcotic Antagonists; Phytotherapy; Plant Extracts; Sesquiterpenes; Zingiberaceae

Abdominal pain is common in the general population and, in patients with irritable bowel syndrome, is attributed to visceral hypersensitivity. We found that oral administration of specific Lactobacillus strains induced the expression of mu-opioid and cannabinoid receptors in intestinal epithelial cells, and mediated analgesic functions in the gut-similar to the effects of morphine. These results suggest that the microbiology of the intestinal tract influences our visceral perception, and suggest new approaches for the treatment of abdominal pain and irritable bowel syndrome.

Topics: Abdominal Pain; Administration, Oral; Analgesics, Opioid; Animals; Cannabinoid Receptor Antagonists; Colon; Dose-Response Relationship, Drug; HT29 Cells; Humans; Indoles; Intestines; Lactobacillus acidophilus; Male; Mice; Mice, Inbred BALB C; Morphine; Naloxone; Narcotic Antagonists; Probiotics; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid; Receptors, Opioid; Receptors, Opioid, mu; Rectum

Dragon's blood, the red sap from Croton urucurana Baill. (Euphorbiaceae) has a profound history of traditional use in conditions such as inflammation, diarrhoea and gastrointestinal distress. Previous studies established its anti-inflammatory, antidiarrhoeal and analgesic properties and in this study we verified its potential to suppress visceral pain, using capsaicin- and cyclophosphamide-induced models of visceral nociception. Mice that received intra-colonic capsaicin (0.3%, 50 microl/animal) or intraperitoneal injection of cyclophosphamide (400 mg/kg) manifested spontaneous nociceptive behaviors or crises, which were significantly suppressed in animal groups treated with red sap (200 and 400 mg/kg, p.o.) or that received N-acetylcysteine (750 mg/kg, i.p.) or morphine (7.5 mg/kg, s.c.), as positive controls. In capsaicin model, the antinociception produced by 200 mg/kg red sap was found to be naloxone-sensitive (2 mg/kg, i.p.), suggesting an opioid mechanism. In tests of open-field and pentobarbital-sleeping time, mice received 200mg/kg red sap showed no significant alterations in either locomotion frequency or on sleeping time, indicating that the observed antinociception is not a consequence of sedation or motor abnormality. These findings highlight the visceral antinociceptive property of Croton urucurana sap and further support its ethno-medical use to alleviate pain associated with gastrointestinal and other related disorders.

Topics: Abdominal Pain; Acetylcysteine; Administration, Oral; Adrenergic alpha-Agonists; Animals; Behavior, Animal; Capsaicin; Clonidine; Croton; Cyclophosphamide; Dose-Response Relationship, Drug; Hypnotics and Sedatives; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Mice; Morphine; Motor Activity; Naloxone; Narcotic Antagonists; Narcotics; Pentobarbital; Plant Extracts; Sleep; Time Factors

To establish a visceral pain model via colorectal distension (CRD) and to evaluate the efficiency of behavioral responses of CRD by measuring the score of abdominal withdrawal reflex (AWR) in rats.. Thirty-eight male SD rats weighing 180-240 g were used to establish the visceral pain model. The rat was inserted intra-anally with a 7 cm long flexible latex balloon under ether anesthesia, and colorectal distensions by inflating the balloon with air were made 30 min after recovering from the anesthesia. Five AWR scores (AWR0 to AWR4) were used to assess the intensity of noxious visceral stimuli. It was regarded as the threshold of the minimal pressure (kPa). For abdominal flatting was induced by colorectal distension.. A vigorous AWR to distension of the descending colon and rectum was found in 100% of the awake rats tested. The higher the pressure of distension, the higher the score of AWR. The distension pressures of 0, 2.00, 3.33, 5.33 and 8.00 kPa produced different AWR scores (P<0.05). The pain threshold of AWR was constant for up to 80 min after the initial windup (first 1-3 distensions), the mean threshold was 3.69+/-0.35 kPa. Systemic administration of morphine sulfate elevated the threshold of visceral pain in a dose-dependent and naloxone reversible manner.. Scoring the AWR during colorectal distensions can assess the intensity of noxious visceral stimulus. Flatting of abdomen (AWR 3) to CRD as the visceral pain threshold is clear, constant and reliable. This pain model and its behavioral assessment are good for research on visceral pain and analgesics.

Topics: Abdominal Pain; Analgesics; Animals; Behavior, Animal; Catheterization; Colon; Dilatation, Pathologic; Disease Models, Animal; Male; Morphine; Naloxone; Narcotic Antagonists; Pain Threshold; Rats; Rats, Sprague-Dawley; Rectum; Reflex; Reproducibility of Results; Time Factors; Viscera

The endogenous opioid system is involved in modulating the experience of pain, the response to stress, and the action of analgesic therapies. Recent human imaging studies have shown a significant tonic modulation of visceral pain, raising the question of whether endogenous opioids tonically modulate the pain of visceral cancer.. Transgenic mice expressing the first 127 amino acids of simian virus 40 large T antigen, under the control of the rat elastase-1 promoter, that spontaneously develop pancreatic cancer were used to investigate the role of endogenous opioids in the modulation of pancreatic cancer pain. Visceral pain behaviors were assessed as degree of hunching and vocalization.. Although mice with late-stage pancreatic cancer displayed spontaneous, morphine-reversible, visceral pain-related behaviors such as hunching and vocalization, these behaviors were absent in mice with early-stage pancreatic cancer. After systemic administration of the central nervous system (CNS)-penetrant opioid receptor antagonists naloxone or naltrexone, mice with early-stage pancreatic cancer displayed significant visceral pain-related behaviors, whereas systemic administration of the CNS-nonpenetrant opioid antagonist naloxone-methiodide did not induce an increase in visceral pain behaviors.. Our findings suggest that a CNS opioid-dependent mechanism tonically modulates early and late-stage pancreatic cancer pain. Understanding the mechanisms that mask this pain in early stage disease and drive this pain in late-stage disease may allow improved diagnosis, treatment, and care of patients with pancreatic cancer.

Topics: Abdominal Pain; Animals; Disease Models, Animal; Female; Immunohistochemistry; Male; Mice; Naloxone; Narcotic Antagonists; Neurotransmitter Agents; Opioid Peptides; Pain Measurement; Pancreatic Neoplasms; Severity of Illness Index; Treatment Outcome

Serotonin (5-HT) is known to be an important mediator in pain modulation. Some centrally acting agents, like selective serotonin reuptake inhibitors (SSRIs), modulate pain. Activation of the endogenous opioid mechanisms or potentiation of analgesic effect by serotonergic and/or noradrenergic pathways might be involved in antinociception of SSRIs. However, peripheral mechanisms of nociception are not clear. In this study, the antinociceptive effect of paroxetine, its interaction with the opioidergic system and serotonin receptors were tested using the writhing test in mice. Paroxetine (5, 10, 20 mg/kg) induced an antinociceptive effect following i.p. administration in writhing test. For the groups in which the antagonists were tested, the dose of paroxetine that caused a significant and equipotent analgesic effect similar to 0.5 mg/kg morphine was selected. Naloxone significantly antagonized the antinociceptive effects of both paroxetine and morphine in a similar pattern and magnitude. Ketanserin (5-HT(2)-receptor antagonist) or ondansetron (5-HT(3)-receptor antagonist) alone did not alter the nociceptive action of acetic acid. While the antinociceptive effect of paroxetine was highly potentiated by ketanserin, ondansetron reduced that antinociception. In conclusion, our results indicate that the antinociceptive effect of paroxetine mainly depends on central opioidergic and serotonergic mechanisms. Peripheral serotonergic mechanisms/receptors may contribute to this antinociceptive effect, especially by 5-HT(3)-receptor subtypes.

Topics: Abdominal Pain; Acetic Acid; Analgesia; Analgesics; Animals; Dose-Response Relationship, Drug; Drug Synergism; Female; Injections, Intraperitoneal; Ketanserin; Male; Mice; Mice, Inbred BALB C; Morphine; Naloxone; Ondansetron; Pain Measurement; Paroxetine; Receptors, Serotonin, 5-HT2; Receptors, Serotonin, 5-HT3

Tramadol (TRM) and metamizol (MTZ) are drugs with complex mechanisms of action, extensively used in combination in pain management. In the present investigation we have evaluated the interaction between MTZ:TRM in the ethacrinic acid writhing test in rats. Dose-response curves (s.c.) were obtained for each drug individually, combined in fixed potency ratios (1:0.3, 1:1, 1:3), and for MTZ in presence of a fixed-dose of TRM (3.5 mg/kg). Interactions were analysed using isobolograms, interaction indexes (INT-I) and ANOVA. We used naloxone (1 mg/kg s.c.) to determine the opioid-component of the effects (ED80). Isobolograms demonstrated antagonism at the ED20, for 1:0.3 and 1:3 mixtures (p<0.01), whereas 1:1 was additive. At the ED50 and ED80 all combinations showed synergy. Fixed-dose experiments demonstrated that treatment (p<0.0001), dose (p<0.0001), and their interaction (p<0.0001) were statistically significant. Naloxone partially antagonized TRM (67%), but not MTZ; the percentage reversal of the combinations was directly related to the dose of TRM in the combination. The results show that the MTZ:TRM interaction on antinociception is synergistic or antagonistic depending on the level of effect. Synergy is demonstrated at 50% or higher levels, thus supporting the results obtained in humans by our group. Below the ED50 antagonism or additivity is present depending on the ratio of the combination. The mechanisms of the interaction remain unknown.

Topics: Abdominal Pain; Acute Disease; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dipyrone; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Antagonism; Drug Interactions; Drug Synergism; Ethacrynic Acid; Male; Naloxone; Narcotic Antagonists; Pain Measurement; Rats; Rats, Sprague-Dawley; Tramadol; Visceral Afferents

Nefopam is a clinically effective analgesic agent used to control mild to moderate pain, whose mechanism of action is unknown. We have investigated the antinociceptive activity of nefopam in the mouse abdominal constriction assay and tail immersion test (48 degrees C). Nefopam was found to possess a high degree of potency against acetic acid-induced visceral nociception (ED50 2.5 mg kg(-1)). In the presence of the opioid receptor antagonists, naloxone or naltrindole, the resulting nefopam dose-response relationships were shifted to the right. Naloxone or naltrindole had no effect upon aspirin (ED50 32.1 mg kg(-1)) or clonidine (ED50 0.061 mg kg(-1)) induced antinociception. Acetorphan (10 mg kg(-1); s.c.), an inhibitor of neutral endopeptidase (EC 3.4.24.11) was able to potentiate nefopam's antinociceptive activity (ED50 1.5 mg kg(-1)). The alpha2-adrenoceptor antagonist, 2-[2-(2-methoxy-1,4-benzodioxanyl)]imidazoline hydrochloride (RX821002; 1 mg kg(-1); s.c.), shifted the dose-response curves for clonidine (ED50 7.1 mg kg(-1)) and nefopam (ED50 5.3 mg kg(-1)) to the right in this assay. Additionally, centrally administered RX821002 (1 microg/5 microl/animal; i.c.v.) reduced both clonidine (ED50 7.2 mg kg(-1)) and nefopam's ED50 15.5 mg kg(-1)) efficacy in the abdominal constriction assay. Nefopam (3 and 7.5 mg kg(-1); s.c.) produced significant antinociceptive effect in the thermal assay. Aspirin and RX821002 were devoid of any significant activity in the tail immersion test. Nefopam was shown to possess RX821002-reversible antinociceptive activity in both the tail immersion test and the abdominal constriction assay. These data suggest the involvement of an opioidergic and noradrenergic component to nefopam's antinociceptive activity in the mouse abdominal constriction assay and tail immersion test. However, the present results are unable to determine if the opioidergic component of nefopam antinociception is through a direct and/or indirect activation of opioid receptors.

Topics: Abdominal Pain; Acetic Acid; Adrenergic alpha-Antagonists; Analgesics; Analgesics, Non-Narcotic; Animals; Clonidine; Dose-Response Relationship, Drug; Drug Interactions; Idazoxan; Injections, Intraventricular; Male; Mice; Naloxone; Naltrexone; Narcotic Antagonists; Nefopam; Pain Measurement; Receptors, Adrenergic; Receptors, Opioid

The effect of a leukotriene D(4) receptor antagonist, (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl(3-dimethyl amino-3-oxo propyl)thio)methyl)thio) propanoic acid (L-660,711; MK-571), was investigated on nociceptive responses in mice using three different assays: acetic-acid-induced abdominal constrictions, formalin response and tail-flick test. MK-571 (8-32 mg/kg, i.v.) produced dose-dependent protection against acetic-acid-induced abdominal constriction (ED(50)=30 mg/kg). The compound (10-80 mg/kg, i.p.) was also effective, in a dose-dependent manner, on the second phase of the formalin response (ED(50)=26 mg/kg). However, it had no effect on the first phase of the formalin response and in the tail-flick test. Naloxone (1 mg/kg, i.v.), an opioid antagonist, almost completely blocked the antinociceptive effect of MK-571 in both acetic-acid-induced abdominal constriction and the second phase of the formalin test. These results provide evidence for an antinociceptive action of MK-571 at peripheral sites and suggest that opioid mechanisms are involved.

Topics: Abdominal Pain; Acetates; Analgesics; Animals; Body Temperature; Leukotriene Antagonists; Male; Membrane Proteins; Mice; Naloxone; Narcotic Antagonists; Pain Measurement; Propionates; Quinolines; Receptors, Leukotriene; Receptors, Opioid