Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caffeine potentiation of ketorolac-induced antinociception in the pain-induced functional impairment model in rats was assessed. Caffeine alone was ineffective, but increased the effect of ketorolac without affecting its pharmacokinetics. Intra-articular administration of adenosine and N6-cyclohexyladenosine (CHA, an adenosine A1 receptor agonist), but not 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680, an adenosine A2A receptor agonist), significantly increased ketorolac antinociception. This effect was not local, as contralateral administration was also effective. Ipsilateral and contralateral administration of adenosine and CHA also increased antinociception by ketorolac-caffeine. Intra-articular 8-Bromo-adenosine cyclic 3',5'-hydrogen phosphate sodium or 8-Bromo-guanosine-3',5'-cyclophosphate sodium (cGMP) given ipsilaterally or contralaterally did not affect ketorolac-induced antinociception. Nevertheless, ipsilateral, but not contralateral, administration of 8-Br-cGMP significantly increased antinociception by ketorolac-caffeine, suggesting a local effect. The results suggest that caffeine potentiation of ketorolac antinociception is mediated, at least partially, by a local increase in cGMP and rule out the participation of adenosine receptor blockade.
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PMID:Effect of coadministration of caffeine and either adenosine agonists or cyclic nucleotides on ketorolac analgesia. 1045 27

More than 2200 subjects were enrolled in the MorphiDex (MS:DM) development program, with a 1:1 (weight:weight) ratio of morphine sulfate (MS) to dextromethorphan hydrobromide (DM). Of the 1400 subjects exposed to MorphiDex, more than 350 subjects were treated for at least 6 months, and over 200 subjects were treated for a year or longer. The clinical population comprised an approximately equal number of men (46.2%) and women (53.8%), ranging in age from 16 to 96 years, and mostly Caucasian (91.8%). The most frequent (54.8%) daily dose of MorphiDex for subjects enrolled in the clinical program was 120 mg or less. Slow DM metabolizers took significantly lower daily doses of MorphiDex than rapid metabolizers without a significant difference in the incidence of adverse events. Plasma bromide concentrations were low and showed a wide margin of safety for both slow and rapid DM metabolizers. There were no clinically significant treatment-related changes in clinical laboratory tests, neurological examinations, or vital signs. The most common adverse events seen in the multiple dose controlled studies were nausea, dizziness, vomiting, somnolence, constipation, confusion, asthenia, headache, and pruritus. With long-term treatment, the prevalence of adverse events was greatest during the first month of MorphiDex exposure and then decreased over time. The incidence of constipation remained fairly constant over time.
J Pain Symptom Manage 2000 Jan
PMID:Long-term safety of MorphiDex. 1068 40

Experimental studies have shown that otilonium bromide (OB) inhibits both baseline and chemically or physically stimulated gastrointestinal motility. The spasmolytic activity of OB in the gastrointestinal tract occurs at doses that do not affect gastric secretion or produce typical atropine-like side-effects. The mechanism of action is composite: interference with calcium ion movement from intra- and extracellular sites; blockade of calcium channels; and binding to muscarinic receptors and tachykinin neurokinin-2 receptors. Pharmacokinetic studies have shown that OB accumulates in the lower intestine and has poor systemic absorption. Clinical studies have confirmed OB as a potent spasmolytic drug with a good tolerability profile. Studies in patients with irritable bowel syndrome demonstrated OB to be superior to placebo and reference drugs in parameters such as pain, abdominal distension and motility. The composite and local mechanism of OB action reduces hypermotility and modulates visceral sensation: factors thought to be responsible for pain improvement recorded in clinical trials. The compound is marketed worldwide and no serious adverse events have been reported as yet, confirming its excellent tolerability.
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PMID:Otilonium bromide: a selective spasmolytic for the gastrointestinal tract. 1068 27

The effect of pinaverium bromide in controlling gastrointestinal symptoms in 61 patients with irritable bowel syndrome was studied, as an open trial. Individually, there was significant relief in abdominal discomfort/pain as well as in bowel symptoms in most of the patients. Abdominal pain was reduced in 49%, stool consistency improved in 74%, straining and urgency decreased in 71% and mucus decreased in 64%. Tolerance to the drug administered was good and side-effects reported were few.
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PMID:Role of pinaverium bromide in south Indian patients with irritable bowel syndrome. 1127 20

Low intrathecal (i.t.) doses of the nitric oxide (NO)-donor 3-morpholinosydnonimine (SIN-1) (0.1-2.0 microg/10 microl) reduced, while higher doses had no effect (5 or 100 microg/10 microl) or increased (10 and 20 microg/10 microl) the mechanical allodynia induced by chronic ligature of the sciatic nerve in rats. SIN-1 (0.1-100 microg/10 microl; i.t.) produced only antinociceptive effect in the rat tail flick test. The inhibitor of guanylate cyclase, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (4 microg/10 microl; i.t.), abolished the antinociceptive effects of SIN-1 in both tests and reduced the effect of high doses of SIN-1 in neuropathic rats. Hemoglobin (100 microg/10 microl; i.t.), a NO scavenger, inhibited the effect of low dose of SIN-1 and reduced the effect of high dose of SIN-1 in neuropathic rats. 8-Bromo-cGMP (125-500 microg/10 microl; i.t.), reduced the mechanical allodynia in neuropathic rats. The NO-synthase inhibitors, NG-nitro-L-arginine (L-NOARG) and NG-monomethyl-L-arginine (L-NMMA) (75-300 microg/10 microl; i.t.) reduced the mechanical allodynia evoked by nerve injury and increased the tail-flick latency, respectively. These effects were reduced and inhibited, respectively, by previous i.t. ODQ. The effect of L-NOARG was enhanced in a non-significant manner by hemoglobin. These results indicate that SIN-1 and NO-synthase inhibitors reduce pain through a spinal mechanism that involves activation of guanylate cyclase. The effects of SIN-1 vary depending on the dose and pain model utilized, but its most sensitive effect seems to be antinociception. However, high doses of the NO-donor can intensify ongoing pain.
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PMID:The dual effect of a nitric oxide donor in nociception. 1128 53

The appropriate choice of anesthesia for patients (pts) undergoing renal transplantation (Ktx) requires minimal toxicity and accurate monitoring for pts at high risk for metabolic, cardiovascular, and respiratory perioperative complications. We evaluated the anesthetic management and postoperative follow-up in pediatric Ktx performed in the last 12 years in our institution. From 1988 to 1999, 75 ASA class II-III pts (45 males, 22 females) younger than 18 years scheduled for Ktx were studied: 49 received a graft from a cadaveric donor (CD) and 26 from a living donor (LD). All pts were treated with dialysis within 24 h before the procedure. Standard monitoring consisted of an electrocardiogram, central venous pressure, non-invasive arterial pressure, pulse oximetry, and inspiratory and expiratory gas analysis. If necessary, an arterial cannula and pediatric pulmonary catheter were introduced. Anesthesia was induced with sodium thiopental, propofol, halothane, or sevoflurane and maintained with isoflurane and/or fentanyl and droperidol in O2:N2O (FiO2 0.4%). As muscle relaxants atracurium or cisatracurium besilate were used, except in allergic pts, in whom vecuronium or rocuronium bromide was administered. Dopamine, 20% mannitol, and furosemide were used to increase diuresis. Continuous morphine and ketoralac infusions were used for postoperative pain relief. The surgical technique was the same in all cases. Complications and renal-function (RF) recovery were evaluated relating to CD and LD using the chi-square test; differences in mean anesthesia and surgical time were evaluated by Student's t-test; survival curves were calculated from the day of Ktx to death or last follow-up and estimated by the Kaplan-Meier method. Values of P below 0.05 were considered significant. Postoperative immunosuppressive therapy was based on cyclosporine together with other conventional drugs. Mean anesthesia time was 228 +/- 65 min. Mean kidney ischemia time for CD was 16.5 +/- 4 h. Four pts (3 CD, 1 LD) died within 72 h postoperatively: 3 due to cardiac failure and 1 to metabolic coma. Six pts showed cardiovascular and 3 had infective complications, all successfully treated. Three pts (2 CD, 1 LD) died within 2 to 12 months after, surgery; 10 (6 CD, 4 LD) had graft failure and are still alive on dialysis; 58 (38 CD, 20 LD) are alive in good health after a mean follow-up of 57.6 +/- 36.6 months (range 12-120 months). Fifteen of 26 pts younger than 12 years (21 CD and 5 LD) recovered RF intraoperatively (10 CD, 5 LD); 1 with CD and 1 with LD showed postoperative graft failure and 2 with CD died within 72 h postoperatively, 22 (18 CD and 4 LD) are alive in good health. This group showed no statistical difference compared to pts older than 12 years. Of 16 pts (15 CD and 1 LD) with body weight (BW) less than 25 kg, 6 showed intraoperative (5 CD, 1 LD) recovery of RF. The 3 deaths were all in CD pts, 2 within 72 h and one 2 months after surgery; only 1 LD had postoperative graft failure. Twelve pts (75%) (12 CD, 80%) are alive in good health. Compared to pts with BW of 25 kg or more, this group showed lower intraoperative recovery of RF (P < or = 0.05). No peri- and postoperative complications occurred in all 26 LD pts (100%). Recent advances in surgery, anesthesia, immunosuppression, and antimicrobial prophylaxis have made Ktx a more predictable procedure even in pediatric pts. For high-risk pts, mortality and morbidity can be controlled by accurate surgical, anesthetic, and postoperative management. Pts younger than 12 years and with BW less than 25 kg are more likely to develop peri- and postoperative complications.
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PMID:Pediatric renal transplantation: anesthesia and perioperative complications. 1131 82

Temporomandibular joint (TMJ) pain conditions are poorly understood. Since formalin is a noxious stimulus widely used in animal behavioral experiments for studying pain mechanisms, the aim of this study was to develop a behavioral model to study the TMJ pain conditions by characterizing the nociceptive behavioral responses induced by the injection of formalin into the TMJ region of rats. NaCl (0.9%) or different concentrations of formalin (0.5, 1.5, 2.5 or 5%) were administrated into the TMJ region. The formalin-induced behavioral responses characterized by moving the mandible, rubbing the orofacial region and flinching the head quickly were quantified for 45 min. The TMJ injection of formalin significantly increased the asymmetrical orofacial rubbing and head flinching behaviors, but not the movement of the mandible with concentrations of 1.5% and above (P<0.05, Dunn's test) when compared with the NaCl (0.9%) injection. These responses were significantly reduced (P<0.05, Mann-Whitney test) by the co-application of lidocaine N-ethyl bromide quaternary salt, QX-314 (2%), and by the administration of intraperitoneal morphine (4 mg/kg) 30 min prior to the TMJ formalin injection. This study demonstrates that the injection of formalin into the TMJ region of rats produces quantitative nociceptive behaviors constituting a novel behavioral model for TMJ pain.
Pain 2001 Nov
PMID:Development of a behavioral model of TMJ pain in rats: the TMJ formalin test. 1169 Jul 32

A 30-year-old man developed paresthesia in the feet, unstable gait and blepharoptosis subsequent to pharyngeal pain while working in a warehouse of imported fruit and vegetable fumigated with methyl bromide and cyanate. Neurological examination showed bilateral blepharoptosis, diplopia, ataxic gait and paresthesia below the inguinal region. The serum concentration of thiociane, a metabolite of cyanide, was within normal limits, but that of bromide was elevated (43.7 mg/l, normal: 3.7-8.6). Thus we diagnosed the patient as intoxication of methyl bromide. Magnetic resonance imaging of the brain (MRI) revealed bilateral symmetrical lesions of high signal intensity in the posterior region of the putamen, the subthalamic nuclei, the dorsal medulla oblongata corresponding to inferior cerebellar peduncles and vestibular nuclei, the inferior colliculi and the periaqueductal gray matter surrounding the oculomotor nucleus of the midbrain. As far as we know, this is the first report of MRI detected cerebral lesions in a case with intoxication of methyl bromide.
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PMID:[A case of chronic methyl bromide intoxication showing symmetrical lesions in the basal ganglia and brain stem on magnetic resonance imaging]. 1180 54

Anesthesia during and after off-pump surgery is critical for the outcome of the procedure. Intubation time has been shown to correlate with ICU time and length of stay. This study is to evaluate the extubation time and predictors of prolonged extubation in this institution. One hundred and sixty consecutive patients during Jan 2001-June 2002, excluding pre-operative tracheostomy (n = 1) were retrospectively reviewed. Anesthetic agents include fentanyl, rocuronium Bromide, midazolam and sevoflurane. Phenylephrine and nitroglycerine were used to maintain adequate arterial pressures. Post-operative pain control was mainly with intravenous fentanyl and oral pain medications. The extubation time was divided into 4 groups; 0-2 h, n = 76, mean = 1.11 +/- 0.5 h; 2-4 h, n = 30, mean = 2.91 +/- 0.5 h; 4-24 h, n = 39, mean = 11.44 +/- 7.3 h; > 24 h, n = 5, mean = 33.3 +/- 21 h. The data were collected and analyzed following the guidelines of National STS cardiac surgery database. All pre-operative risk factors included: Age (> 70 yrs vs < or = 70 yrs), gender (male vs female), diabetes (yes vs no), hypertension (yes vs no), morbid obesity (yes vs no), renal insufficiency (yes vs no), chronic obstructive lung disease (yes vs no), history of cerebrovascular accident (yes vs no), smoking (yes vs no), dyslipidemia (yes vs no), history of myocardial infarction (MI) (yes vs no), history of congestive heart failure (CHF) (yes vs no), unstable angina (yes vs no), left ventricular ejection fraction (LVEF) (> 40% vs < or = 40%), left main (LM) lesion (LM > 50% vs LM < or = 50%), intra-aortic balloon pump (IABP) used (yes vs no) and time between operating and closing (> 4.30 h vs < or = 4.30 h) were used to predict failed early extubation (2 h). More than 50 per cent of the patients were extubated in less than 2 h (1.11 +/- 0.5 h) and only 5 patients were extubated after 24 h. Univariate analysis revealed old age, diabetes, MI, CHF, LVEF < or = 0.4 and the use of IABP are the predictors (p < 0.05) of failed early extubation. Multivariate analysis of these variables revealed old age with adjusted odds ratio of 4.6 (95% CI = 1.5-13.7) p < 0.01, diabetes with adjusted odds ratio of 3.2 (95% CI = 1.3-7.5) p < 0.01 and IABP used with adjusted odds ratio of 4.3 (95% CI = 1.3-14.6) p = 0.02 are the predictors of fail early extubation. The findings suggested early extubation is possible in OPCAB surgery and attention should be made when operate in patients who have old age, diabetes, and IABP used.
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PMID:Off-pump coronary artery bypass surgery: evaluation of extubation time and predictors of failed early extubation. 1286 66

The great majority of patients with duodenal ulcer (DU) given a single oral dose (50 mg) of dicetel (pinaverium bromide)--a selective blocker of calcium channels--showed optimization of vegetative reactivity and vegetative support of physical and mental activities. This contributes to relief of psychovegetative syndrome of the modulation of dysfunctions of proximal gastrointestinal tract (GIT). The addition of dicetel to combined treatment of PH shortened healing of DU, relieved pain, stopped gastric and intestinal dyspepsia, corrected motor-tonic defects of the proximal GIT caused by dysfunction of different links of the regulatory-adaptive system.
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PMID:[Effects of dicetel on gastrointestinal motility and vegetative dysfunction in patients with duodenal ulcer]. 1452 Sep 42


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