Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insect neurotransmitter proctolin can affect different behavioural parameters in rats after intracerebroventricular administration. Proctolin decreased the horizontal exploratory activity and induced a long-lasting analgesia in a hot-plate test. Proctolin lenghthened the passive avoidance latency of rats after post-trial treatment and also in the pre-retention test situation. The self-stimulation rate of rats was significantly diminished after i.c.v. proctolin administration. Proctolin also induced in rat and mouse ileum in vitro a dose-dependent contraction of the gut smooth-muscle that can be blocked by atropine. The results show that an invertebrate neuropeptide (or its fragments) can also be active in mammals. The physiological relevance of the effects observed recently is unknown.
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PMID:The insect neuropeptide proctolin can affect the CNS and the smooth=muscle of mammals. 611 30

A series of ceruletide analogues were tested in order to evaluate the structural requirements for activity on gut and brain. The effects studied were: contraction of the guinea pig gallbladder and stimulation of the exocrine pancreatic secretion in the dog after intravenous (IV) administration, for activity on the gut; analgesia (hot plate test) and sedation (reduction of spontaneous rearing activity) in mice by subcutaneous (SC) route, for activity on the brain. The structural requirements were roughly the same for central and peripheral activities. Possible mechanisms for the antinociceptive effects of ceruletide in humans were proposed.
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PMID:Structural requirements of ceruletide-like peptides for activity on gut and brain. 628 98

Opiate receptors in the central nervous system may be classified according to pharmacological, behavioural, or binding studies. Classical mu-receptors probably have beta-endorphin as an endogenous ligand, and seem to be involved in the modulation of pain perception, low-frequency acupuncture analgesia, and the stimulation of prolactin, growth hormone and thyroid-stimulating hormone release. Met-enkephalin is likely to be an endogenous ligand for the delta-receptors, which predominate in the basal ganglia and limbic systems; such receptors may tonically inhibit the release of corticotrophin-releasing factor. It has been suggested that the newly-described kappa-receptors may inhibit the release of vasopressin and gonadotrophin-releasing factor; dynorphin may be their endogenous ligand. Endogenous opiates controlling cardiovascular and respiratory reflexes are likely to activate mu-receptors, while high-frequency acupuncture may alleviate the symptoms of opiate withdrawal by allowing an increase in Met-enkephalin to activate delta-receptors. In the periphery, beta-endorphin is concentrated in the corticotrophs of the anterior pituitary, and is cosecreted with ACTH and related peptides. Circulating Met-enkephalin originates in the gut, sympathetic nervous system and adrenal medulla. Met-enkephalin may also be extracted from carcinoid tumours and phaeochromocytomas. Elevations in circulating Met-enkephalin may occur in certain disease states with cardiovascular and psychiatric manifestations. However, manipulation of endogenous or exogenous opiates has as yet no certain place in any clinical situation.
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PMID:Opiate receptors: enkephalins and endorphins. 630 48

In a double-blind study using patients' subjective reports as indices of analgesia, the relative analgesic potency of intramuscular and oral nalbuphine was determined in 104 postoperative patients. Effects of single doses of 3 and 9 mg of intramuscular nalbuphine were compared with those of 15- and 45-mg oral doses of nalbuphine by means of a parallel study design (26 patients per treatment group). When both intensity and duration of analgesia are considered (i.e., total analgesic effect), oral nalbuphine is 1/4 to 1/5 as potent as intramuscular nalbuphine. In terms of peak effect, however, oral nalbuphine is only 1/10 as potent. The oral/parenteral potency ratio for total effect is close to those obtained by Houde et al. in studies of morphine (1/6), metopon (1/5), hydromorphone (1/5), and oxymorphone (1/6) and suggests that oral nalbuphine undergoes substantial biotransformation on first pass through gut mucosa and liver. Since intramuscular nalbuphine is approximately equipotent to morphine, it should be feasible to equal the analgesia induced by the usual intramuscular doses of morphine with reasonable oral doses of nalbuphine. Although nalbuphine is a mixed agonist/antagonist analgesic, no psychotomimetic reactions were observed.
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PMID:Analgesic effect of intramuscular and oral nalbuphine in postoperative pain. 700 84

Ingestion of placenta or amniotic fluid by rats has been shown to enhance ongoing opioid-mediated antinociception, but does not, by itself, produce antinociception. This enhancement is produced by an active substance(s) in placenta and amniotic fluid that we have termed POEF for placental opioid-enhancing factor. Previous research has shown that enhancement requires mediation by the gastrointestinal system: gastric vagotomy blocks enhancement produced by ingested placenta; amniotic fluid injected SC or IP does not produce enhancement. The present study was designed to distinguish between two possible explanations for the blockade of the POEF effect produced by gastric vagotomy: that afferent information arising in vagal gastric receptors conveys the critical information to the CNS, or that disruption of vagal efferent action on digestion blocks the manufacture or activation of the POEF molecule in the gut. Famotidine is an H2-histamine receptor antagonist that reduces gastric acid and pepsin secretion to an extent at least as great as gastric vagotomy. Rats treated with either famotidine or a vehicle were fed placenta or a control substance, then stimulated with vaginal/cervical probing to produce antinociception that is partly opioid mediated. Famotidine did not block POEF enhancement of vaginal/cervical stimulation-induced analgesia in a tail flick latency test. These results suggest that enhancement by POEF does not require normal digestive processes or other processes inhibited by famotidine.
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PMID:Blockade of digestion by famotidine pretreatment does not interfere with the opioid-enhancing effect of ingested amniotic fluid. 771 1

Loperamide effects on hepatobiliary function, analgesia and gut transit were studied in mice. Varying doses of the antidiarrheal drug, loperamide, were administered to mice by intracerebroventricular, intravenous, subcutaneous and intragastric routes. Gut motility was determined by intestinal transit of India ink, analgesia by warm water tail flick latency, and hepatobiliary function by retention of the anionic dye, sulfobromophthalein in plasma and liver. When given by all routes at modest doses, loperamide slowed intestinal transit. Analgesia, a centrally mediated opiate effect, was only detected after intracerebroventricular or subcutaneous loperamide at high, near-toxic doses. Elevations of plasma and liver sulfobromophthalein were noted at routes and doses which slowed gut transit, well below those needed for analgesia. Intragastric loperamide at one fortieth its LD50 caused marked elevation of sulfobromophthalein levels and gut slowing, but no analgesia. Sulfobromophthalein elevation and gut slowing by intragastric loperamide were not affected by spinal cord transection but were reversed by naltrexone, an opiate antagonist. Non-toxic doses of loperamide slow gut transit and modify hepatobiliary function in mice by opiate actions at peripheral sites.
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PMID:Loperamide effects on hepatobiliary function, intestinal transit and analgesia in mice. 817 10

Advances in ventilator technology and recent findings in pathophysiological mechanisms have resulted in a remarkable decrease in classical volume controlled and pressure controlled ventilation modes as treatment for severe acute respiratory insufficiency. New modes of ventilatory support enabling and encouraging patients' spontaneous breathing, such as Biphasic Positive Airway Pressure (BIPAP) and Airway Pressure Release Ventilation (APRV), make it possible to adapt ventilatory support better and more easily to suit patients' needs than conventional modes of controlled ventilation. Preservation and support of patients' spontaneous breathing improves pulmonary gas exchange and reduces stress imposed by mechanical ventilation. The 'invasiveness' of mechanical ventilation is reduced and patients' comfort is less disturbed. Through this, the need for sedation and analgesia is considerably reduced and this may minimize systemic side-effects and complications from analgo-sedation and mechanical ventilation. The drugs should be administered in an adequate, individually adapted manner. Routinely-ordered and fixed combinations of drugs administered continuously are not adequate adequate as they further carry the risk of overdosing a different single drug with the corresponding side-effects (depression of respiratory drive, gut motility, etc.).
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PMID:[Ventilation modes and strategies in intensive care medicine]. 917 39

The new class of antiinflammatory and analgesic drugs, the selective cyclooxygenase (COX-2) inhibitors, which promise to be devoid of the types of toxicity associated with nonsteroidal antiinflammatory drugs (NSAID), especially adverse gastrointestinal effects, are under clinical trial but are not yet available for use. All NSAID, including those most recently introduced, exhibit nonselectivity of action, producing therapeutic blood levels that inhibit constitutive COX-1 and deplete tissue protective prostaglandins. Among NSAID, the diclofenac/misoprostol combination (Arthrotec) is unique in possessing an active component, misoprostol, to help prevent NSAID induced gastrointestinal damage. Ulcer damage and associated serious complications probably represent only the tip of the iceberg in relation to clinically significant side effects associated with the use of NSAID. In this context, metaanalysis of 8 large multicenter studies reported here has shown that patients taking NSAID show a mean decrease in hemoglobin over 4 - 12 weeks' assessment, with some 10-20% of patients exhibiting clinically significant decreases (> or = 1 g/dl) early in treatment. Patients taking diclofenac/misoprostol showed significantly less of a decline in hemoglobin and up to 50% fewer clinically significant decreases than patients receiving diclofenac alone. The misoprostol component of diclofenac/misoprostol may also help to restore homeostasis in tissues other than the gut. Inhibition of the activity or release of various tissue damaging agents and inflammatory cytokines, e.g., thromboxane and interleukin 1, are described, as are in vivo animal studies that have revealed synergistic or potentiating analgesic and antiinflammatory activities between misoprostol and NSAID, particularly diclofenac. Clinical studies in postsurgical dental pain in more than 500 patients have now shown enhanced analgesia, with greater relief over a longer period, for the diclofenac/misoprostol combination compared with diclofenac alone. The relevance of these findings to pain and inflammation control in arthritis is discussed. Enhanced control of morning stiffness provided by diclofenac/misoprostol, possibly also the result of misoprostol/diclofenac synergy, is also reported, and the development of an objective system that measures 24 hour ambulatory activity is described. Using this Numact recorder, improved mobility in patients receiving diclofenac 75 mg/misoprostol 200 microg was observed compared with patients treated with diclofenac 75 mg slow release. Further studies are being performed employing magnetic resonance imaging both to assess antiinflammatory effects in joint soft tissue architecture and to assess whether the synergistic stimulatory effects of diclofenac and misoprostol on human osteoarthritic cartilage that have been reported in vitro are clinically evident. A growing body of evidence supports the view that the diclofenac/misoprostol combination provides an improved therapeutic ratio over diclofenac alone, not only by improving gastrointestinal safety but also by enhancing analgesic/antiinflammatory effects.
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PMID:Diclofenac/misoprostol: novel findings and their clinical potential. 959 52

2-Arachidonoyl-glycerol (2-Ara-GI) has been isolated from various tissues and identified as an endogenous ligand for both cannabinoid receptors, CB1 and CB2. Here we report that in spleen, as in brain and gut, 2-Ara-GI is accompanied by several 2-acyl-glycerol esters, two major ones being 2-linoleoyl-glycerol (2-Lino-Gl) and 2-palmitoyl-glycerol (2-Palm-Gl). These two esters do not bind to the cannabinoid receptors, nor do they inhibit adenylyl cyclase via either CB1 or CB2; however, they significantly potentiate the apparent binding of 2-Ara-Gl and its apparent capacity to inhibit adenylyl cyclase. Together these esters also significantly potentiate 2-Ara-Gl inhibition of motor behavior, immobility on a ring, analgesia on a hot plate and hypothermia caused by 2-Ara-Gl in mice. 2-Lino-Gl, but not 2-Palm-GI, significantly inhibits the inactivation of 2-Ara-Gl by neuronal and basophilic cells. These data indicate that the biological activity of 2-Ara-Gl can be increased by related, endogenous 2-acyl-glycerols, which alone show no significant activity in any of the tests employed. This effect ('entourage effect') may represent a novel route for molecular regulation of endogenous cannabinoid activity.
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PMID:An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity. 972 Oct 36

Tramadol and morphine were compared for treatment of severe chronic pancreatitis pain and their interaction with gut motor function. Oral tramadol or morphine doses were titrated double-blinded and randomized for five days in 25 patients and pain, side effects, bowel function, orocecal and colonic transit, anal resting pressure, and rectal distension thresholds were measured. Pain intensities (mean+/-SD, 0 = none, 100 = unbearable) before treatment and on day 4 were 75+/-19 and 8+/-13 with tramadol (P < 0.001), and 65+/-21 and 5+/-6 with morphine (P < 0.001). On day 4, 67% of patients with tramadol and 20% with morphine rated their analgesia as excellent (P < 0.001) with mean respective doses of 840 mg (range: 80-1920) and 238 mg (20-1125). Orocecal transit was unchanged after five days of tramadol, but increased with morphine (P < 0.05). More patients had prolonged colonic transit times with morphine by day 5 (P < 0.05). Rectal distension threshold pressures increased only with tramadol (P < 0.01). It is concluded tramadol and morphine are potent analgesics in severe chronic pancreatitis pain when individually titrated. Tramadol interfered significantly less with gastrointestinal function and was more often rated as an excellent analgesic than morphine.
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PMID:Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis. 1038 80


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