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PubMed1990

Evaluation of analgesic agents in recurring headache compared with other clinical pain models.

The efficacy of three preparations (placebo, analgesic agent, and analgesic plus antihistaminic agent) were compared in a double-blind crossover study in subjects with recurring headaches. It was confirmed that headache as a pain model does not show the usual return of pain with as the effects of a single analgesic dose wear off. Consequently, there is no "peak effect," and the rationale for comparing treatments by "area under the curve" calculations is weakened. Greater efficacy was demonstrated for the analgesic over the placebo and for the analgesic and antihistaminic combined over the analgesic alone in several parameters. Slopes of straight lines derived as a quadratic function of pain versus time data proved to be a more effective discriminator between treatments than area under the curve calculations from the same data.

Acetaminophen↗
PubMed2003

Analgesic use and pain coping among patients with haemophilia.

Pain is an important consequence of bleeding episodes in haemophilia. Previous research has included pain frequency and severity among measures of illness-related disability and quality of life in haemophilia, but little systematic evidence exists about analgesic use and pain coping in haemophilia. This paper reports cross-sectional findings from a national survey of patients with severe haemophilia type A and type B. Respondents provided information about pain frequency, pain coping strategies (using the haemophilia-adapted CSQ), use of analgesics and other drugs, and described any concerns they had about their drug use. Participants registered with comprehensive care haemophilia centres did not differ from the rest of the sample on any of the factors recorded. Over one-third of participants expressed concerns about their drug use, the most frequent of which were about dependence on prescribed analgesics. Pain frequency was the most important predictor of analgesic use, but pain coping, and specifically negative thoughts about pain, was associated with concerns about drug use independently of other factors, including analgesic use and pain frequency. Further research will be needed to evaluate possible interventions to promote more effective pain coping in haemophilia, and to examine the possible effects of pain coping on illness outcomes beyond analgesic use, such as well-being and quality of life.

Adaptation, Psychological↗
PubMed2003

A QSAR analysis to explain the analgesic properties of Aconitum alkaloids.

Aconitum roots are traditionally prescribed for the management of different types of painful affections in Asiatic countries. A quantitative structure-activity relationship (QSAR) analysis was performed to study the effect of chemical substitutes in the analgesic potency of alkaloids available in Chinese Aconitum roots. Using the CAChe program package for biomolecules, molecular modelling was performed in 12 alkaloids previously tested in a model of acetic acid-induced writhing in rats. The ED50 (micromol/kg) was used as the activity parameter. Structural parameters were compared between alkaloids with an aroyl/aroyloxy group at R14 and alkaloids with the aroyloxy group at R4. Single linear regression analyses were performed in order to find the parameters explaining activity. Alkaloids with an aroyl/aroyloxy group at R14 exhibited the highest potency (significantly less ED50). The stability parameters were different between groups, e.g. total energy was -8.0 +/- 0.4 in the potent analgesic alkaloids and -6.7 +/- 0.3 in the weak analgesic alkaloids (P = 0.001). The reactivity index of C2', C3' and C5' of the aromatic ring was also different between groups, e.g. the reactivity index of C5' was 40.8 +/- 0.6 in potent analgesic alkaloids and 48.1 +/- 0.6 in weaker analgesic alkaloids (P < 0.001). Several structural parameters explained analgesic activity of alkaloids, being the reactivity index of C5' on the aromatic group the most important factor (r = 0.89; P < 0.001).

Aconitum↗
PubMed1998

Derangement of serotonin system in migrainous patients with analgesic abuse headache: clues from platelets.

Accumulating evidence indicates that serotonin (5-HT) may be involved in the process of analgesic-induced headache transformation. In order to clarify this hypothesis, we investigated the 5-HT system in migraine patients with analgesic abuse headache by using platelets as a neuronal model. Our results revealed a significant decrease in platelet 5-HT content in these patients compared to migraine patients and nonheadache controls (179.24 +/- 10.18, 451.22 +/- 14.35, and 480.22 +/- 13.98 ng/10(9) platelets, respectively; P < 0.001). This biochemical result was well correlated with a significant decrease (P < 0.001) in platelet dense body number observed in these patients (5.9 +/- 0.4 and 9.2 +/- 0.6 granules/10 platelets. For migraine patients with and without analgesic abuse headache, respectively). Beside the 5-HT depletion, the presence of numerous large intracytoplasmic vacuoles formed from the surface-connecting canaliculi system was found in this condition. Such a finding has not been previously described. The total area occupied by these vacuoles was significantly greater (P < 0.01) in migraine patients with analgesic overuse than in migraine patients and nonheadache controls (249.2 +/- 19.5, 164.1 +/- 19.5, and 183.1 +/- 20.3 nm2/cells, respectively). As this canaliculi system plays a significant role in the platelet secretory response, such dilatation may imply an excessive release of substances from this system. Based on this platelet model, we suggest that excessive use of analgesics alters the central 5-HT system by depleting 5-HT from its storage sites and results in the hyposerotonergic state. This analgesic-induced 5-HT alteration may be a possible mechanism of headache transformation observed in this condition.

Adult↗
PubMed2002

Pharmacology of systemic analgesics.

Systemic administration of analgesic drugs is still the most widely used method for providing pain relief in acute painful situations. Opioids may be selected on the basis of their physicochemical characteristics and their diffusion index to the brain. But in clinical practice, their very steep concentration-analgesic effect relationship remains a critical aspect of opioid therapy. Thus, small fluctuations in plasma concentrations of opioids may lead to profound fluctuations in analgesic effect when their plasma and effect-site concentrations are near the minimum effective analgesic concentration (MEAC). Combining drugs acting on different mechanisms of nociceptive modulation offers benefits from additive/synergistic effects and will decrease the incidence of their adverse effects. Evidence-based reviews showed that effective pain relief using non-opioid analgesics relied on paracetamol supplemented with non-steroidal anti-inflammatory drugs (NSAIDs). The role of COX-2 selective inhibitors (CSIs) in acute pain relief still requires further evaluation. NSAIDs, CSIs and paracetamol share the property of morphine sparing in situations of severe (post-operative) pain. CSIs may be beneficial in patients in whom post-operative bleeding is a major surgical risk as the effects of NSAIDs on coagulation may last for days. Finally, low-dose ketamine infusions remain a worthwhile addition to opioid therapy. Analgesic concentrations of ketamine are 1/5th to 1/10th the anaesthetic concentration and exert significant inhibition on N-methyl-d-aspartate (NMDA) receptor activation.

Acetaminophen↗
PubMed2003

Synthesis and evaluation of analgesic, anti-inflammatory and antimicrobial activities of 6-acyl-3-piperazinomethyl-2-benzoxazolinones.

In this study, 16 new 6-difluorobenzoyl-3-piperazinomethyl-2-benzoxazolinones were synthesized by Mannich reaction. Their chemical structures were proven by IR, 1H-NMR and elemental analysis. The compounds were screened for their analgesic and anti-inflammatory activities. A modified Koster test, using acetylsalicylic acid (ASA, CAS 50-78-2) as the reference drug, was used to assess analgesic activity. The anti-inflammatory activity was evaluated by the carrageenan induced hind-paw oedema test. The analgesic activities of all compounds were higher than their anti-inflammatory activities and therefore the prominent analgesic actions of the compounds are thought to be due to a central effect. The microbiological effects of the compounds were evaluated in vitro against various pathogenic fungi and bacteria using the microdilution method. Most of the compounds were found to be inactive against bacteria and fungi. One of the compounds (31) possessed considerable analgesic activity as well as moderate antibacterial activity against S. aureus. Another compound (3m) showed analgesic and antifungal activities comparable to those of ASA and fluconazole (CAS 86386-73-4), respectively.

Analgesics, Non-Narcotic↗
PubMed1987

[Analgesic consumption in the Federal Republic of Germany. The extent and the risk groups].

An analysis of still unpublished sales statistics shows that during 1976-1983 the annual sales of all analgesic package units remained relatively stable (about 115 million units per year), while the consumption of large packings mostly preferred by analgesic abusers increased from 8.13 to 11.28 million (units of 100 tablets). The annual per capita consumption of analgesic substances (1983) was 18.2 g. Among these, drugs containing salicylate and phenazone headed the list, whereas phenacetin consumption is increasingly on the downgrade (0.87 g per capita). 95% of all analgesics are used outside of the clinics. Furthermore, 80% of them are purchased on the prescription-free market. High consumption of analgesics can be assumed in 5% of the normal population. Analgesic abuse is more prevalent in women, especially in some industrial areas.

Analgesics↗
PubMed2001

Laparoscopic nephroureterectomy to exclude upper urinary tract malignancy associated with analgesic nephropathy.

BACKGROUND AND PURPOSE: Analgesic abuse is a potential cause of end-stage renal disease. Such patients bear an elevated risk of developing malignancies, predominantly transitional-cell carcinoma. We report our experience with laparoscopic nephroureterectomy carried out in patients with analgesic nephropathy to exclude upper urinary tract malignancy. All patients were scheduled to be put on the waiting list for cadaveric renal transplantation. PATIENTS AND METHODS: Since 1996, nine women and two men with a long-term history of analgesic abuse have undergone laparoscopic nephroureterectomy at our hospital. The median age was 63 years (range 51-70 years). All patients had developed end-stage renal failure secondary to heavy analgesic abuse with a median duration of 14 years (range 7-40 years). The median interval from the beginning of hemodialysis to laparoscopic nephroureterectomy was 36 months (range 6-76 months). RESULTS: The median operative time was 99 minutes (range 55-170 minutes). There were no conversions to open surgery. Two complications occurred, and three patients required blood transfusions. The median hospital stay lasted 5 days (range 2-12 days), and the median convalescence was 20 days (range 6-44 days). In seven patients, histopathologic examination of the kidney revealed changes attributable to analgesic abuse. None of the patients had a transitional-cell carcinoma, but in two patients, a renal-cell carcinoma stage pT1cN0cM0 grade 2 was detected. CONCLUSION: Patients with analgesic nephropathy bear an elevated risk for the development of transitional-cell or renal-cell carcinoma. In these patients, laparoscopic nephroureterectomy combines minimally operative invasiveness with a maximum of diagnostic safety.

Aged↗
PubMed1989

Patterns of PRN analgesic drug administration in children following elective surgery.

Conducted chart review study of 114 4- to 14-year-olds hospitalized for elective surgery to investigate analgesic medication patterns. Correcting for body weight and different drug potencies, correlations were examined between analgesics, child age, painfulness of recovery, and seriousness of surgical procedure. Weight-adjusted analgesics prescribed and delivered PRN were unrelated to painfulness of procedure and age. Expert ratings of the seriousness of anticipated sequelae were found to be a modest but significant predictor of analgesics. Results suggest that PRN prescription of analgesics in children essentially guarantees very low drug delivery without achieving individualized pain management. Possible interpretations and suggestions for research into effects of practitioner attributions of seriousness on clinical decision making are discussed, along with implications for other explanations of inadequate analgesic practices.

Adolescent↗
PubMed1998

Adding ketamine in a multimodal patient-controlled epidural regimen reduces postoperative pain and analgesic consumption.

UNLABELLED: We designed this double-blind study to evaluate the effect of adding small-dose ketamine in a multimodal regimen of postoperative patient-controlled epidural analgesia (PCEA). Ninety-one patients, ASA physical status I-III, undergoing major surgery, received a standardized general anesthesia and epidural catheterization in an appropriate intervertebral space after surgery. A PCEA device was programmed to deliver a regimen of morphine 0.02 mg/mL, bupivacaine 0.8 mg/mL, and epinephrine 4 microg/mL, with the addition of ketamine 0.4 mg/mL (ketamine, n = 45) or without (control, n = 46). The mean visual analog pain scale (VAS) scores during cough or movement for the first 3 days after surgery were higher in the control group than in the ketamine group (P < 0.05), whereas the mean VAS score at rest for the first 2 days were higher in the control group than in the ketamine group (P < 0.05). Furthermore, patients in the control group consumed more multimodal analgesics than patients in the ketamine group for the first 2 days (P < 0.05). The sedation scores and the incidence of side effects (pruritus, nausea, emesis, sleep deprivation, motor block, and respiration depression) were similar between the two groups. We conclude that adding ketamine 0.4 mg/mL in a multimodal PCEA regimen provides better postoperative pain relief and decreases consumption of analgesics. IMPLICATIONS: Many studies have evaluated one or a combination of two analgesics for postoperative pain control, but few have examined a multimodal approach using three or four different epidural analgesics. This study demonstrates an additive analgesic effect when ketamine is added to a multimodal analgesic treatment.

Analgesia, Epidural↗
PubMed2001

A systematic review of the peripheral analgesic effects of intraarticular morphine.

The analgesic effects of intraarticular morphine are controversial. To systematically evaluate the effects, we performed a review of the literature and a metaanalysis of the peripheral effects of morphine injected intraarticularly. Research databases were searched to identify articles in which peripheral analgesic effects of morphine were studied in patients undergoing arthroscopic knee procedures under local, regional, or general anesthesia. The review was performed on three issues: does morphine injected intraarticularly produce analgesia, is it a dose-dependent effect, and, if so, is the effect systemic or mediated via peripheral opioid receptors? Visual analog score (VAS) and analgesic consumption were studied during the early phase (0-2 h), intermediate phase (2-6 h), and late phase (6-24 h) postoperatively after injection of morphine intraarticularly. Metaanalysis of these effect variables was performed by the weighted-analysis technique, and the essential homogeneity assumption was tested by the chi(2) test. Forty-five articles could be identified in which the effects of morphine were studied in a prospective, randomized manner, and 32 of these studies included a placebo control. Pooled analyses of data from 19 studies suitable for metaanalysis showed an improvement in analgesia after morphine compared with placebo in the order of 12-17 mm on the VAS during all three phases of treatment. Studies with high quality scores showed somewhat smaller improvements. Total analgesic consumption could not be analyzed statistically, but the number of studies showing decreased analgesic consumption or no differences between groups was identical (six and six). No clear dose-response effect was seen when VAS was used as a measure of pain, but it was seen when area under the curve was used as a measure of pain. A systemic effect of peripherally-injected morphine was not possible to exclude because of the very limited data available. We conclude from this metaanalysis that intraarticularly administered morphine has a definite but mild analgesic effect. It may be dose dependent, and a systemic effect cannot be completely excluded.

Analgesics, Opioid↗
PubMed1995

Role of pertussis toxin-sensitive G-proteins in the analgesic and anesthetic actions of alpha 2-adrenergic agonists in the rat.

BACKGROUND: alpha 2 Adrenoceptors are coupled to G-proteins sensitive to pertussis toxin (PTX) in the locus coeruleus. At this site, the hypnotic response to dexmedetomidine, an alpha 2 agonist, can be blocked by pretreatment with PTX. G-proteins sensitive to PTX may also be involved in the transduction of anesthetic and analgesic responses to alpha 2 agonists at supraspinal or spinal sites. To address this question the effects of pretreatment with PTX administered intracerebroventricularly, intrathecally, or a combination of the two were examined on the MAC for halothane, and the anesthetic-sparing and analgesic effects of a systemically administered alpha 2 agonist, dexmedetomidine. METHODS: Rats were cannulated intracerebroventricularly, intrathecally, and with a combination of intracerebroventricular/intrathecal and treated with PTX (0 and 2.5 micrograms intracerebroventricularly; 0 or 0.5 microgram intrathecally; 0 + 0 or 2.5 + 0.5 intracerebroventricular-intrathecal)). After 7 days, either the analgesic (tail-flick latency) or the MAC-sparing effects of a calculated 50% effective dose of dexmedetomidine were measured. To confirm that intracerebroventricularly administered PTX was effective, ribosylation of G-proteins was assessed in periventricular brain tissue. RESULTS: The analgesic action of dexmedetomidine was blocked by PTX intrathecally but not by PTX via the intracerebroventricular route. The MAC-sparing action of dexmedetomidine was not blocked by PTX via the intrathecal or intracerebroventricular routes alone or in combination. Yet, intracerebroventricularly administered PTX effectively ribosylated the G-proteins. CONCLUSIONS: Taken together with the authors' previous report, these data suggest that the hypnotic and the analgesic responses to dexmedetomidine are transduced via PTX-sensitive G-protein-coupled alpha 2 adrenoceptors but at separate sites (analgesic-spinal; hypnotic-locus coeruleus). Further studies are needed to localize the precise site(s) for the MAC-sparing effect of dexmedetomidine and to establish whether PTX-sensitive G-proteins are involved in this response.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1999

The relationship between the visual analog pain intensity and pain relief scale changes during analgesic drug studies in chronic pain patients.

BACKGROUND: Most analgesic drug studies in humans quantify drug action based on verbal reports of pain intensity and pain relief. Although measures of pain intensity and pain relief show a good overall correlation, it is not known if they relate to each other consistently over time Such consistency is necessary if both measures are used to depict analgesic drug action versus time. This study examined in chronic pain patients if the relationship between visual analog pain intensity and pain relief scores was consistent during two analgesic drug studies. METHODS: Data from two independently performed analgesic drug studies were analyzed using linear regression. Data were split into pain intensity and pain relief scores recorded before and after patients' experience of maximum analgesia (>90% of maximum pain relief). The slopes of the linear regression line depicting pain intensity versus pain relief scores before and after maximum analgesia were statistically compared. RESULTS: The slope of the linear regression line before and after maximum analgesia was significantly different in both drug studies (nonoverlapping 95% confidence intervals), -2.16+/-0.57 versus -1.05+/-0.10 and -1.47+/-0.26 versus -1.09+/-0.07, respectively. These results are compatible with the observation that patients indicating the same pain intensity before and after maximum analgesia reported a different magnitude of pain relief. CONCLUSIONS: The relationship between visual analog pain intensity and pain relief scores changed systematically during both analgesic drug studies. The authors hypothesize that patients' interpretation of the pain relief scale had changed during the studies and therefore suggest using the pain intensity scale to quantify analgesic drug action over time.

Adult↗
PubMed2006

Multifactorial preoperative predictors for postcesarean section pain and analgesic requirement.

BACKGROUND: The study aimed to determine predictive factors for postcesarean pain and analgesia using an assessment of pain threshold and suprathreshold thermal stimuli as well as degree of somatization and anxiety. METHODS: Thirty-four healthy parturients scheduled for cesarean delivery under subarachnoid anesthesia were enrolled. Preoperative thermal pain threshold, intensity, and unpleasantness to heat stimuli applied to arm and lower back, State Trait Anxiety Inventory, and patient expectation for postoperative pain and need for analgesia were assessed. After surgery, overall, resting, and movement pain and analgesic consumption were recorded. Prediction of pain and analgesic use outcomes was made by principal component factor analysis, followed by stepwise linear regression. RESULTS: Resting pain was predicted by two factors, thermal pain and unpleasantness and patient expectation (r2 = 0.26, P < 0.01), evoked pain by thermal pain threshold in the back (r2= 0.20, P < 0.009), composite pain by thermal pain and unpleasantness and preoperative blood pressure (r2 = 0.28, P < 0.008), intraoperative analgesic need by preexisting pain (r2 = 0.22, P < 0.006), recovery room analgesia by thermal pain threshold and State Trait Anxiety Inventory (r2 = 0.27, P < 0.01), and total analgesic need by State Trait Anxiety Inventory (r2 = 0.22, P < 0.01). These models predicted the upper twentieth percentile of composite pain scores and analgesic requirement with sensitivity of 0.71 to 0.80 and specificity of 0.76 to 0.80. CONCLUSIONS: The authors' results suggest a meaningful combination of preoperative patient responses from physical and psychological tests yields a valid multifactorial predictive model for postoperative pain and analgesic requirement with significant improvements over individual predictive variables.

Analgesics↗
PubMed2001

Analgesic domains of interferon-alpha.

Interferon-alpha (IFNalpha) is not only an immunoregulatory factor, but is also an analgesic molecule. We ever reported that there exist distinct domains in IFNalpha molecule that mediate immune and analgesic effects respectively and inferred that the analgesic domain locates around the 122nd Tyr residue of IFNalpha molecule in the tertiary structure. After the 36th Phe residue, which was located closely to the 122nd Tyr residue in the tertiary structure, was mutated to Ser using site-directed mutagenesis, the analgesic activity of this mutant lost completely, but the antiviral activity of IFNalpha still maintained 40.5% of wild type IFNalpha. The results suggest that the 36th Phe residue is one of the constituent for the analgesic domain of IFNalpha and inferred that the analgesic domain of IFNalpha consists of the 122nd Tyr and the residues around the 122nd in the tertiary structure, which include the 36th Phe.

Analgesics↗
PubMed1997

Is decreased use of analgesics in Alzheimer disease due to a change in the affective component of pain?

Relatively low use of nonsteroidal anti-inflammatory drugs (NSAIDs) and other analgesics has been noted in patients with probable Alzheimer disease (AD). Although this finding has been explained by a decline in patients' capacities to communicate about pain, self-report on pain of cognitively impaired elderly have been shown to be just as reliable as those of cognitively unimpaired elderly. However, previously published studies were aimed primarily at quantifying pain. Considering the various limbic areas affected in AD, a change also in the more qualitative, affective component of pain might be the cause of the low use of analgesics. Because affective disorders are highest in the early and middle stages of AD and decrease in the final stage, it was hypothesized in the present study that not only would the number of AD patients using analgesics would be lower than among a control group but, moreover, analgesic use would be lower in the early and middle stages of AD than in the final stage. The hypothesis was tested by comparing drug use (NSAIDs and analgesic non-NSAIDs) among 66 AD patients with that among 70 elderly people without dementia. The percentage of AD patients using analgesics was indeed significantly lower than among controls, but drug use was not dependent on the stage of AD. Consequently, our findings only partly support the hypothesis.

Aged↗
PubMedDate not supplied

Over-the-counter analgesics: a toxicology perspective.

The decision to use any analgesic is a balance of benefit and risk. In the case of analgesics, it is important to balance the therapeutic benefit against both the risk in therapeutic use and the risk (and ease of treatment) in overdose. Paracetamol in therapeutic dose carries little risk of adverse events. Less than 0.1% of the estimated 30 million paracetamol users in the United Kingdom attend hospital with a paracetamol overdose each year, and approximately 200 people die, most of whom presented late or did not receive antidote, N-acetylcysteine, within 12 hours. Nonsteriodal anti-inflammatory drugs (NSAIDs) have greater adverse effects in therapeutic use than paracetamol but also have a lower incidence of severe features or death in overdose. There is no antidote available for NSAID poisoning. Aspirin carries both significant adverse effects in therapeutic dose and a substantial risk in overdose, for which there is no antidote. Its risk-benefit profile is probably the poorest of all analgesics currently available over-the-counter (OTC); this is reflected in current trends both in analgesic use and overdose figures. Although a number of options to reduce deaths from poisoning by OTC analgesics have been considered, few are practical, and all must take account of the public health benefits provided by these drugs. A perspective should be retained that the vast majority of the population in Australia, the United States, the United Kingdom, and Denmark derive therapeutic benefit from OTC analgesics and do not take them in overdose. The majority of those who do take overdoses come to little or no harm. Management of serious poisoning by paracetamol, aspirin, or NSAIDs remains a medical challenge.

Acetaminophen↗
PubMedDate not supplied

The effect of sunlight on postoperative analgesic medication use: a prospective study of patients undergoing spinal surgery.

OBJECTIVE: Exposure to natural sunlight has been associated with improvement in mood, reduced mortality among patients with cancer, and reduced length of hospitalization for patients who have experienced myocardial infarction. Our aim was to evaluate whether the amount of sunlight in a hospital room modifies a patient's psychosocial health, the quantity of analgesic medication used, and the pain medication cost. METHODS: A prospective study of pain medication use was conducted in 89 patients undergoing elective cervical and lumbar spinal surgery where they were housed on either the "bright" or "dim" side of the same hospital unit. Analgesic medication was converted to standard morphine equivalents for interpatient comparison. The intensity of sunlight in each hospital room was measured daily and psychologic questionnaires were administered on the day after surgery and at discharge. RESULTS: Patients staying on the bright side of the hospital unit were exposed to 46% higher-intensity sunlight on average (p = .005). Patients exposed to an increased intensity of sunlight experienced less perceived stress (p = .035), marginally less pain (p = .058), took 22% less analgesic medication per hour (p = .047), and had 21% less pain medication costs (p = .047). Age quartile was the only other variable found to be a predictor of analgesic use, with a significant negative correlation (p <.001). However, patients housed on the bright side of the hospital consistently used less analgesic medications in all age quartiles. CONCLUSION: The exposure postoperatively of patients who have undergone spinal surgery to increased amounts of natural sunlight during their hospital recovery period may result in decreased stress, pain, analgesic medication use, and pain medication costs.

Age Factors↗