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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In response to concerns over the clinical relevance of analgesic testing paradigms which involve acute nociceptive stimuli, the present research examined the utility of the conditioned place preference (CPP) paradigm as a novel approach for determination of analgesic drug efficacy against chronic nociception. Rats display preferences for environments that have been previously paired with positively reinforcing drugs; whether place preference to the negatively reinforcing effects of analgesic drugs in an animal model of chronic pain occurs is yet unknown. The present research sought to determine whether animals experiencing chronic pain would display a place preference for an environment paired with analgesic drug treatment. Persistent inflammatory nociception was induced by unilateral injections of complete Freund's adjuvant (0.1 ml) into the rat hind paw. Place preference to the opiate agonist morphine, the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the non-steroidal anti-inflammatory drug (NSAID) indomethacin was examined in 3 separate experiments. Rats received 8 counter-balanced conditioning trials (4 drug, 4 no-drug) of 60 min each with various drug doses (morphine: 3.0 and 10.0 mg/kg; indomethacin: 2.5 and 5.0 mg/kg; MK-801: 0.03, 0.1 and 0.3 mg/kg, i.p.) or vehicle serving as the reinforcing stimuli in a 3 compartment (2 stimuli, 1 neutral) place preference apparatus. In general, morphine place preference was observed in both inflamed and non-inflamed groups; inflamed groups exhibited enhanced morphine place preference than non-inflamed groups. MK-801 produced a low-dose place preference in inflamed animals; higher doses of MK-801 produced a place aversion in both inflamed and non-inflamed groups. Indomethacin failed to produced place preference in either inflamed or non-inflamed groups. These data demonstrate that the negatively reinforcing properties of analgesic drugs can be assessed via the CPP paradigm. In addition, this paradigm offers greater clinical relevance as animals determine drug efficacy without the involvement of high-intensity, phasic nociceptive stimulation.
Pain 1994 Sep
PMID:Conditioned place preference paradigm: a novel approach for analgesic drug assessment against chronic pain. 783 85

Eicosanoids may be important factors for tumor cell proliferation, metastatic formation, and development of cancer cachexia. The present study has evaluated the effect of anti-inflammatory treatment on tumor progression in clinical cancer. Patients (n = 135) with insidious or overt malnutrition due to generalized malignancy (various kinds of solid tumors) and an expected survival of more than 6 months were randomized by a computer-based algorithm to receive placebo, prednisolone (10 mg twice daily), or indomethacin (50 mg twice daily) p.o. until death. Patient groups were stratified in the randomization procedure for sex, tumor type, stage, nutritional state, and previous tumor treatment, and biochemical, physiological, and some functional variables (Karnowsky index, fatigue and pain score). A majority of these variables was then registered during the follow-up. Indomethacin and prednisolone treatment maintained Karnowsky index, while placebo-treated patients experienced a decreased index. Indomethacin-treated patients suffered less pain and consumed less additional analgetics compared to the other patient groups. Indomethacin prolonged mean survival compared to placebo-treated patients from 250 +/- 28 days to 510 +/- 28 days (P < 0.05). Survival analysis on observations from all patients treated with either indomethacin or prednisolone demonstrated a significantly prolonged survival by anti-inflammatory treatment compared to placebo treatment (log rank, P < 0.03). The results suggest that not only may prostaglandin synthesis inhibition offer palliative support to patients with solid advanced cancer, but it may also impact on pathways that ultimately determine outcome.
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PMID:Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. 792 4

There is experimental evidence that inhibition of cyclooxygenase with nonsteroidal anti-inflammatory drugs may decrease cholesterol gallstone formation and mitigate biliary pain in gallstone patients. The mechanisms by which NSAIDs exert these effect are unclear. In a prospective, controlled clinical trial we examined the effects of oral indomethacin on the composition of human gallbladder bile. The study included 28 patients with symptomatic cholesterol or mixed gallstones. Of these, 8 were treated with 3 x 25 mg indomethacin daily for 7 days prior to elective cholecystectomy while 20 received no treatment and served as controls. Bile and tissue samples from the gallbladder were obtained during cholecystectomy. Indomethacin tissue levels in the gallbladder mucosa, as assessed by HPLC, were 1.05 +/- 0.4 ng/mg wet weight, a concentration known to inhibit effectively cyclooxygenase activity. Nevertheless, no differences between the treated and untreated groups were found in the concentrations of biliary mucus glycoprotein (0.94 +/- 0.27 versus 0.93 +/- 0.32 mg/ml) or total protein (5.8 +/- 0.9 versus 6.4 +/- 1.3 mg/ml), cholesterol saturation (1.3 +/- 0.2 versus 1.5 +/- 0.2), or nucleation time (2.0 +/- 3.0 versus 1.5 +/- 2.0 days). However, biliary viscosity, measured using a low-shear rotation viscosimeter, was significantly lower in patients receiving indomethacin treatment (2.9 +/- 0.6 versus 5.6 +/- 1.2 mPa.s; P < 0.02). In conclusion, in man oral indomethacin decreases bile viscosity without alteration of bile lithogenicity or biliary mucus glycoprotein content.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indomethacin decreases viscosity of gallbladder bile in patients with cholesterol gallstone disease. 831 87

The aim of this study was to demonstrate significant factors behind elevated resting energy expenditure in weight-losing cancer patients. Therefore, weight-losing cancer patients (n = 60), with normal liver and kidney function tests, were randomized to receive one of four drug treatments for 5 days: (a) Propranolol 80 mg x 2 (beta-adrenoceptor blockade); (b) Indomethacin 50 mg x 2 (prostaglandin synthesis inhibition); (c) Morphine 5 mg x 3 (pain relief) or (d) Placebo x 2. A reference group of healthy well-nourished individuals were examined outside the formal randomization protocol and they received Propranolol 80 mg x 2. The cancer patients were randomized by a computer based algorithm stratifying for measured resting energy expenditure (REE), body composition, biochemical tests, previous therapy, tumour type and tumour stage. Resting energy expenditure was measured by indirect calorimetry in the morning after an overnight fast before and after drug treatment. beta-blockade reduced REE significantly in cancer patients from 1416 +/- 95 kcal day-1 to 1160 +/- 63 kcal day-1 (P < 0.02) and from 1472 +/- 69 vs, 1398 +/- 63 kcal day-1 (P < 0.01) in the well-nourished reference individuals. The reduction found in cancer patients (10%) was significantly larger than that in the group of reference patients (5%), (P < 0.01). Indomethacin, morphine or placebo did not induce any significant alteration in energy expenditure in our cancer patients. Propranolol treatment was associated with a significant reduction in plasma concentrations of free fatty acids (FFA), but not in plasma glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of mechanisms behind elevated energy expenditure in cancer patients with solid tumours. 838 58

Indomethacin commenced before operation was compared with postoperative indomethacin administration for pain relief in patients after elective thoracic surgery. In addition to indomethacin, all patients received i.v. opioids titrated to their individual requirements. There was no significant difference between the two groups in quality of pain relief, in cumulative opioid requirement or in the incidence of adverse effects. The quality of pain relief compared well with previous similar studies using this technique.
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PMID:Preoperative indomethacin for pain relief after thoracotomy: comparison with postoperative indomethacin. 847 73

The clinical features of idiopathic stabbing headache ("jabs and jolts syndrome") were studied in 38 patients who were diagnosed throughout a 1-year period. Mean age at the onset of symptoms was 47.1 years +/- 14.5 (SD), and a clear female preponderance was demonstrated (female/male ratio = 6.6). Painful attacks were ultrashort, i.e. virtually all attacks in more than two thirds of cases lasted only one second. The frequency of attacks varied immensely, ranging from 1 attack per year to 50 attacks daily. The pain paroxysms usually occurred with an irregular or sporadic temporal pattern. The localization of painful attacks was reported frequently as unifocal, usually in the orbital area, but also multifocal patterns were observed, the attacks frequently changing location from one area to the next. The majority of attacks occurred spontaneously, and accompanying phenomena were reported only rarely. Indomethacin treatment (75 mg daily) seemed to have a complete or partial effect in most patients treated as such (n = 17).
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PMID:Idiopathic stabbing headache (jabs and jolts syndrome) 866 81

Indomethacin is the drug of first choice in chronic paroxysmal hemicrania with clear relief of pain as a diagnostic criterion. In a few cases, indomethacin is not tolerated because of side effects. Therefore, the efficacy of carbamazepine, verapamil, sumatriptan, acetylsalicylic acid, and oxygen as drugs in the prophylactic or acute treatment of chronic paroxysmal hemicrania was studied in a prospective open trial with 10 patients suffering from chronic paroxysmal hemicrania. The trial results, in accordance with a review of the literature, suggest that acetylsalicylic acid (and probably naproxen and diclofenac) and verapamil are the most effective drugs of second choice in chronic paroxysmal hemicrania. The efficacy of sumatriptan in this condition needs still to be clarified, although there is evidence for partial efficacy. Carbamazepine and oxygen did not show any significant influence on chronic paroxysmal hemicrania.
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PMID:Alternatives in drug treatment of chronic paroxysmal hemicrania. 878 75

Indomethacin-responsive headaches can present in the orofacial region. According to the classification of headache by the International Headache Society, indomethacin-responsive headaches include chronic paroxysmal hemicrania, hemicrania continue, benign cough headache, benign exertional headache, and sharp, short-lived headache pain syndrome. The mechanism by which indomethacin produces its therapeutic effects in these headache disorders remains speculative. A review of indomethacin-responsive headaches and eight cases in which the presenting symptom was orofacial pain are reported. Because these headache disorders are rare but may present as facial pain, they should be considered in the differential diagnosis of orofacial pain. A comprehensive evaluation prior to performing irreversible treatments is essential when an idiopathic facial pain presents to the dental clinician.
J Orofac Pain 1995
PMID:Benign indomethacin-responsive headaches presenting in the orofacial region: eight case reports. 899 27

A 31-year-old woman had left-sided miosis, ptosis, and hypopigmented iris probably since birth. At 22, she developed intermittent headaches, always in the left frontotemporal region. These headaches lasted from 1 to 2 days and recurred every 1-2 months. Pain attacks were pressing-pulsatile in character, moderate in intensity, and frequently accompanied by nausea, vomiting, and moderate phono- and photophobia. Various treatment alternatives, such as conventional analgesics and ergotamine failed to improve the attacks. Pizotifen was partially effective. The results of pupillometry and evaporimetry studies were consistent with a 3rd neuron sympathetic hypofunction on the symptomatic side. Autonomic studies and clinical features were consistent with a congenital Horner's syndrome. Conceivably, a sympathetic hypofunction may play a role in the pathogenesis of such headache or in its lateralization. Indomethacin and sumatriptan both seemed to provide absolute pain relief. Some clinical features, the fact that the IHS criteria for migraine are fulfilled and that sumatriptan is efficient, demonstrate the similarity to migraine. The coexistence of strict unilaterality of pain and the probable, complete response to indomethacin indicate a similarity to hemicrania continua in its remitting form. Further information on the effect of sumatriptan in hemicrania continua will help clarify the position of this case vs. hemicrania continua. At this stage, it is probably not possible to classify this case properly.
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PMID:Congenital (?) Horners syndrome and ipsilateral headache. 921 66

Prostaglandins and thromboxanes are products of arachidonic acid metabolism via the cyclooxygenase (CO) enzyme and are responsible for the pain and swelling common to sites of inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the production of these substances and are used in the treatment of inflammatory diseases such as arthritis. However, one of the major side-effects of NSAID therapy is gastric ulceration. It is possible that inhibition of prostaglandin production and a related increase in the formation of leukotrienes via the 5-lipoxygenase (5-LO) enzymatic pathway are responsible for attracting inflammatory cells, causing local sites of inflammation and producing ulceration. To determine the effects of 5-LO inhibition on this hypothesis, studies were performed in rats to evaluate the effects of tepoxalin, a dual CO/LO inhibitor on leukotriene B4 levels in gastric mucosa and neutrophil adhesion in mesenteric venules. In rats, chronic oral administration of an NSAID, indomethacin (2 mg/kg daily over 4 days), resulted in 40% mortality, accompanied by intestinal adhesions and perforations when evaluated 24 h after the fourth dose of drug. Additionally, neutrophil adhesion was increased in the mesenteric venules and cell infiltration was evident in the mesenteric interstitium. These gastrointestinal side-effects were inhibited in a separate group of rats administered tepoxalin (20 mg/kg, p.o) 30 min prior to each daily indomethacin treatment. Further studies were performed to determine tepoxalin's effects on early events associated with NSAID-induced gastrointestinal inflammation, including neutrophil adhesion, lipid peroxide generation and LTB4 production. Indomethacin (100 mg/kg, p.o.) produced elevated levels of LTB4 in rat gastric mucosa 90 min after administration. Additionally, neutrophil adhesion in mesenteric venules was increased at this dose and with the administration of another NSAID, naproxen. No generation of lipid peroxides was evident in the gastric mucosa at this timepoint. Tepoxalin (up to 400 mg/kg, p.o.) did not have an effects on gastric mucosal LTB4 generation and lipid peroxide levels. A decrease in neutrophil adhesion was observed at the highest dose. In another study, pretreatment with tepoxalin (ED50=7.5 mg/kg, p.o.) or the selective 5-LO inhibitor zileuton (100 mg/kg, p.o.) prevented the increases in gastric mucosal LTB4 levels and neutrophil adhesion induced by indomethacin (100 mg/kg, p.o.). These data suggest that LO inhibition may play a vital role in the prevention of NSAID-induced gastric inflammation, providing insight into the lack of ulcerogenicity with tepoxalin and new approaches to anti-inflammatory therapy which may prevent gastric side effects.
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PMID:Effects of tepoxalin, a dual inhibitor of cyclooxygenase/5-lipoxygenase, on events associated with NSAID-induced gastrointestinal inflammation. 922 51


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