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PubMed1996

Relation of cognitive coping and catastrophizing to acute pain and analgesic use following breast cancer surgery.

This study investigated the relation of cognitive coping and catastrophizing to acute postoperative pain and analgesic use. Fifty-nine women who had just undergone breast cancer surgery rated their pain on 3 consecutive days and completed a self-report measure of cognitive coping and catastrophizing prior to hospital discharge. Analgesic use over the 3-day period was tabulated from pharmacy records. Based on prior research, it was hypothesized that increased catastrophizing and decreased use of cognitive coping strategies would be associated with greater pain and analgesic use. Results partially confirmed these hypotheses. Catastrophizing, but not cognitive coping, was associated with individual differences in pain intensity and analgesic use. Additional analyses indicated that age was a significant predictor of both catastrophizing and postoperative pain. Specifically, younger patients were more likely to catastrophize and to report increased postoperative pain. Theoretical and clinical implications of these findings are discussed.

Adaptation, Psychological↗
PubMed1980

Animal pharmacology of oxapadol (MD 720111), a new non-narcotic analgesic.

Oxapadol is a non-narcotic analgesic with an unusual chemical structure. It possesses analgesic activity in 4 species similar to that of other non-narcotic reference analgesics. It also shows antipyretic and antiinflammatory effects and in the analgesic dose range is devoid of undesirable neurological, gastro-intestinal and cardiovascular side-effects.

Analgesics↗
PubMed2000

Wound closure tramadol administration has a short-lived analgesic effect.

PURPOSE: To evaluate the effects of tramadol administration at wound closure on postoperative pain and analgesic requirements in patients undergoing laparoscopic cholecystectomy. METHODS: In a prospective, randomized, double-blind study 80 patients were allocated into two groups (n = 40 in each) to receive either 200 mg tramadol or placebo i.v. at the time of wound closure. Postoperatively, all patients received tramadol from a patient-controlled analgesia (PCA) device. Pain, analgesic consumption, vital signs and side effects were recorded postoperatively for 24 hr. RESULTS: Administration of 200 mg tramadol at the time of wound closure was associated with a short-lived (60 min) reduction in pain scores and PCA consumption compared with placebo. Although the time to first request for analgesia after surgery was longer in patients who received tramadol at wound closure, there was no difference between the two groups with respect to pain scores or to the requirements of postoperative analgesia over the next 23 hr. The cumulative PCA consumption of tramadol in 24 hr was 139.4+/-108 and 102.4+/-106 mg in the placebo and tramadol groups, respectively (P = 0.06). CONCLUSIONS: Wound closure administration of 200 mg tramadol had a short-lived (60 min) analgesic effect but did not affect the long-term pain scores or analgesic requirements after laparoscopic cholecystectomy.

Adult↗
PubMed1999

Use of sedatives, analgesics and neuromuscular blocking agents in Danish ICUs 1996/97. A national survey.

OBJECTIVE: To assess the use of sedatives, analgesics and neuromuscular blocking agents (NMBAs) in patients requiring mechanical ventilation in Danish Intensive Care Units (ICUs). DESIGN: Questionnaires were mailed in December 1996 to all Departments of Anaesthesiology listed in the Annual Directory of Danish Hospitals. The questionnaires asked about the use of sedatives, analgesics and NMBAs in patients on mechanical ventilation in the ICU. RESULTS: Forty-nine questionnaires were received from a possible 53 ICUs with ventilators (response rate 92.5%). Sedatives and analgesics were given to patients on mechanical ventilation at virtually all the ICUs surveyed (60% used the combination routinely). The frequency of use was influenced by both the level of ventilatory support and the type of underlying disease. Opioids, benzodiazepines and propofol were employed most commonly, in particular by continuous infusion. NMBAs were used in 65% of the ICUs surveyed in less than 20% of the total number of patients in the respective ICU. Overall 98% of the ICUs reported the occurrence of some kind of side effect secondary to the sedative treatment, but in most ICUs they were reported to occur in less than 20% of the patients. CONCLUSION: Sedatives and analgesics are widely used in patients requiring mechanical ventilation in Danish ICUs. NMBAs are only used in a few patients. The frequency of use is correlated to the level of ventilatory support required and to the kind of respiratory disease.

Analgesics↗
PubMed2003

Systematic evaluation of pain in neonates: effect on the number of intravenous analgesics prescribed.

OBJECTIVE: To document the effect of systematic evaluation of pain in neonates on prescription of intravenous analgesics in a level-III neonatal intensive care unit (NICU) as a marker of increased awareness of treating and preventing pain. METHODS: Retrospective analysis of the number of yearly prescribed vials of intravenous analgesics in a level-III NICU during a period before (1996-1999) and after (2000 to August 2002) introduction of a multidimensional pain scale. Correction was carried out by multiple regression analysis for clinical co-variables (admissions, days on parenteral nutrition, days on respiratory support, surgical procedures), which also might explain changes in prescription of analgesics. Postoperative length (hours) of administration of analgesics was calculated in a group of infants (1996-2001) who all received cryotherapy for threshold retinopathy of prematurity (ROP) before (1996-1999) and since (2000-2001) introduction of pain evaluation. RESULTS: The number of yearly prescribed vials increased from 3140+/-619 (mean+/-SD) to 5915+/-675 ( P<0.005). There is also a significant increase in the number of surgical interventions ( P<0.05) but not in days on respiratory support, days on parenteral nutrition or in number of admissions. After correction for the number of surgical procedures, the increase in prescribed vials remained significant ( P<0.05). In infants who received cryotherapy, a significant increase in length of postoperative analgesia (65-107 h, P<0.01) was documented. Even after correction for the increased postoperative length of ventilation, duration of postoperative analgesia remained significantly ( P<0.05) longer. CONCLUSIONS: Systematic evaluation of pain increased awareness of treating and preventing pain in neonates, even after correction for clinical co-variables. This increase was not associated with an increase in potential side-effects (length of respiratory support, length of parenteral nutrition).

Acetaminophen↗
PubMed2004

Dialogues on complex analgesic strategies for difficult pain syndromes.

Although the use of oral analgesics for the control of cancer pain has been demonstrated to be successful in most patients, some patients will fail to respond to pharmacological therapy or will suffer unacceptable adverse effects. Experience is accumulating that when adverse effects prevail with oral opioid administration, the analgesic response may be improved by changing the drug and/or the route of administration. Switching to an alternative opioid may further improve the balance between analgesia and adverse effects. Despite optimal systemic opioid treatment, in some complicated circumstances it is necessary to find different solutions, including the neuraxial administration of multiple drugs with different characteristics, which are difficult to manage. Three case reports illustrate how complex could be the analgesic approach using multiple analgesic regimens and different routes of administration to effectively manage complex pain syndromes commonly defined as unresponsive.

Administration, Oral↗
PubMed1985

The influence of analgesic drugs in road crashes.

The involvement in road crashes of two classes of drug referred to as analgesics is discussed. Evidence for the effect on traffic safety of each drug group is examined in terms of their behavioural pharmacology and of the available epidemiological data. In the case of the antipyretic analgesics, such as aspirin, there is no evidence to suggest any causative involvement in road crashes. In view of the striking differences in the supply and manner of use of the legal and illegal narcotic analgesics, these are examined separately. The behavioural pharmacology of intravenously administered heroin suggests that any drug induced deficit in driving performance is not due to any effect on psychomotor function, but might be expected from the effect of the drug on mood states. Methadone, as used in treatment schedules for narcotic dependence produces no significant effect on measures of human skills performance. Epidemiological data are contradictory though the suggestion is that the involvement of the narcotic analgesic drugs in road crashes is unlikely to be a source of significant concern. A suggestion is made that a closer examination be undertaken of the involvement in road crashes of the more widely available narcotic drugs codeine and propoxyphene when they are taken together with alcohol.

Accidents, Traffic↗
PubMed1983

Models for clinical assessment of oral analgesics.

Renewed interest in analgesic models has been stimulated by the development of several new nonsteroidal anti-inflammatory drugs. Many of these new analgesic agents appear to have higher peak effects and longer durations of action than acetylsalicylic acid. Sensitive models are necessary to determine the dose-effect relationships and relative analgesic efficacies of these new agents. The basic principles of clinical methods--double-blinding, identical appearance of study medications, and random allocation of treatments to subjects--must be adhered to. However, additional precautions must also be taken. The choice of pain models and further subdivision of subjects within a pain model are critical for assay sensitivity. The dental pain model has become popular because the surgical procedures can be easily categorized, and each subpopulation is relatively homogeneous. There now is a body of data that substantiates the assay sensitivity of the dental pain model, and its usefulness in predicting the general analgesic efficacy of nonsteroidal anti-inflammatory drugs. Other pain models, including general postsurgical, orthopedic postsurgical, and postpartum pain, also have demonstrated adequate assay sensitivity to determine the relative efficacy of new nonsteroidal anti-inflammatory drugs.

Administration, Oral↗
PubMed1983

Effects and risks of psychotropic and analgesic combinations.

Psychotropic substances combined with simple analgesics are a common pharmacologic denominator in the dependency complex. More than 95 percent of patients studied took preparations containing barbiturates; the remaining few subjects used analgesics combined with caffeine. Dependence on compound analgesic preparations usually develops in patients with headaches--migraine, tension headaches, and other complex forms--since ergotamine-containing preparations are generally effective only at the onset of an attack, and prophylactic administration is, therefore, common. Once dependence has developed, reduction or discontinuation of the medication is typically followed after one or two days by an increase in the intensity of the pain. This may cause the patient to revert to these preparations in an attempt to reduce pain and may lead to an unfortunate vicious cycle. Therefore, cessation of psychotropic analgesic combinations is essential in the treatment of chronic pain.

Adult↗
PubMed1988

Analgesic efficacy of piroxicam in the treatment of postoperative pain.

Two randomized, double-blind, single-dose studies were conducted to assess the analgesic efficacy and safety of piroxicam for the treatment of moderate or severe postoperative pain. Study 1 evaluated the analgesic efficacy of piroxicam 20 mg compared with that of codeine sulfate 60 mg and placebo. A final patient population of 149 subjects rated pain intensity and pain relief at one half hour and one hour following treatment and then hourly for six hours, with a global assessment made at the completion of 24 hours. Piroxicam 20 mg was significantly more efficacious than placebo for all analgesic variables, including the sum of the pain intensity differences (SPID), total pain relief (TOTAL), percent SPID, duration of effect, and time to remedication. Codeine 60 mg was significantly superior to placebo for percent SPID and some hourly measures. Piroxicam 20 mg was significantly more effective than codeine 60 mg for percent SPID and a few hourly measures including time to remedication. Study 2 assessed the efficacy of piroxicam 20 mg or 40 mg compared with aspirin 648 mg and placebo. Sixty patients rated their pain intensity and relief hourly for 12 hours and at 24 hours after administration of study medication. Both doses of piroxicam were significantly more effective than placebo from Hours 2 to 12 for pain intensity difference (PID) and relief scores, as well as for SPID and TOTAL. Aspirin was significantly more effective than placebo from Hours 2 to 8 for relief and Hours 2 to 10 for PID as well as SPID and TOTAL. Piroxicam 40 mg was significantly more effective than aspirin 648 mg for SPID, TOTAL, and hourly measures beginning with Hour 6 through Hour 12. Piroxicam 20 mg was significantly better than aspirin for a few hourly measures: Hours 7 to 9 for relief and Hour 7 for PID. In addition, effects of piroxicam 20 mg had a significantly longer duration than aspirin. Similarly, piroxicam 20 mg had a significantly longer time to remedication compared with aspirin and placebo. The results of these studies provide evidence in support of the longer duration of analgesic efficacy of piroxicam compared with codeine or aspirin in patients with postoperative pain.

Analgesics↗
PubMed1987

Characterization of the analgesic effects of the benzodiazepine antagonist, Ro 15-1788.

Three experiments were carried out in rats to evaluate the analgesic effects of the benzodiazepine antagonist, Ro 15-1788. Expt. 1 demonstrated a diazepam reversible analgesic effect of Ro 15-1788 using the tail-flick test. Expt. 2 analyzed the effects of Ro 15-1788 in the hot-plate test at various doses. Low doses of Ro 15-1788 proved analgesia 20 min after drug injection, whereas high doses had no analgesic effect on the 20 min test, but were effective on the 50 min test. Expt. 3 demonstrated that the opiate antagonist, naloxone, had no effect on analgesia produced by Ro 15-1788 in the hot-plate test. The analgesic effects of Ro 15-1788 may be attributable to its reported anxiogenic properties.

Analgesics↗
PubMed1991

Synergistic analgesic interactions between the periaqueductal gray and the locus coeruleus.

Opiates modulate pain perception at a number of different levels within the central nervous system and the importance of synergistic spinal and supraspinal influences have been well documented. In the present study we demonstrate synergistic interactions between the periaqueductal gray and locus coeruleus. Administered either systemically or intracerebroventricularly (i.c.v.), ethylketocyclazocine elicits a potent naloxonazine-sensitive analgesia, indicating a mu 1 action. mu 1 Receptors also play a major role in opioid analgesic mechanisms in the periaqueductal gray and the locus coeruleus. However, microinjection of EKC into either the periaqueductal gray or locus coeruleus failed to elicit an analgesic response at any dose tested (0.1-20 micrograms) and, in additional studies, antagonized the analgesic actions of coadministered morphine or [D-Ser2,Leu5]enkephalin-Thr6 (DSLET). However, the simultaneous administration of EKC into both the periaqueductal gray (10 micrograms) and the locus coeruleus (10 micrograms; total combined dose 20 micrograms) produced a potent naloxonazine-sensitive analgesia greater than that observed with 50 micrograms i.c.v. These results suggest that EKC is a partial mu 1 agonist which lacks the efficacy to elicit analgesia when microinjected into either of the two brain regions alone. However, when exposed to several regions at once, either through simultaneous microinjections into the periaqueductal gray and locus coeruleus or by injection into the ventricle, EKC is a potent mu 1 analgesic. These results point out the existence of synergistic supraspinal interactions between the periaqueductal gray and the locus coeruleus, similar to the spinal/supraspinal interactions observed previously.

Analgesics↗
PubMed1991

Genetic influences in opioid analgesic sensitivity in mice.

Studies of various strains of mice revealed marked differences in their analgesic sensitivity towards morphine (mu), U50,488H (kappa 1) and naloxone benzoylhydrazone (NalBzoH; kappa 3). Sensitivity to mu and kappa analgesia varied independently of the other. Analgesic sensitivity to morphine remained relatively consistent among 3 different nociceptive assays for each strain. However, the sensitivity of an individual strain to NalBzoH remained highly dependent upon the assay used. CD-1 mice were sensitive to NalBzoH in all 3 assays, but in BALB/c mice NalBzoH produced analgesia only in the hot plate and cold water tail-flick assays. In Swiss-Webster mice, NalBzoH was active in the radiant heat and cold water tail-flicks but inactive in the hot plate. Although the levels of mu, kappa 1 and kappa 3 binding in whole brain homogenates did vary somewhat, they did not correlate with analgesic sensitivity. These results suggests that the genetic controls over mu and kappa analgesia operate independently and further illustrate the many difficulties in evaluating potential analgesics.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1980

Tonic analgesic effects of delta 9-tetrahydrocannabinol as measured with the formalin test.

The analgesic effects of delta 9-tetrahydrocannabinol (THC), the psychoactive component of marihuana, were tested using the formalin test. Rats were treated with either THC (5 mg/kg or 10 mg/kg) or a placebo by gavage 4 h before the formalin test for analgesia was initiated. THC produced a highly significant analgesic effect against both phasic pain and tonic pain. THC is discussed as a model for the development of new analgesics or as a suitable analgesic if used with another potentiating drug.

Analgesics↗
PubMed1981

Influence of naloxone and methysergide on the analgesic effect of clomipramine in rats.

The effects of the tricyclic antidepressant clomipramine were studied in two analgesic tests in rats: (1) vocalization threshold response; and (2) scored behavioral response to electric shock to the tail. Clomipramine (20-50 mg/kg i.p.) produced analgesia, decreasing behavioral response scores and increasing vocalization threshold. Morphine also reduced the response scores in the second test. Naloxone (0.8 mg/kg i.p) or methysergide (20 mg/kg i.p.) (no effect when given alone) abolished the analgesic effect of clomipramine as evaluated by vocalization threshold response. Naloxone alone (0.6 or 2 mg/kg i.p.) increased the behavioral response at 20 and 30 V but did not modify the score at 40 V. Naloxone reduced the analgesic effect of clomipramine or morphine in the behavioral test. These results suggest that the analgesic effect of clomipramine could involve both serotonergic and endorphin central systems.

Analgesics↗
PubMed1982

Effect of peptides on the development of tolerance to buprenorphine, a mixed opiate agonist-antagonist analgesic.

The subcutaneous administration of buprenorphine to male Sprague-Dawley rats produced a dose-dependent analgesia and hyperthermia in a dose range of 0.25-2 mg/kg. The subcutaneous administration of buprenorphine (0.5 mg/kg) twice a day for 4 days resulted in the development of tolerance to its analgesic and hyperthermic actions. Daily administration of melanotropin release inhibiting factor (Pro-Leu-Gly-NH2) or cyclo (Leu-Gly) (2 mg/kg s.c.) for 4 days, inhibited the development of tolerance to buprenorphine, as evidenced by greater analgesic and hyperthermic responses to buprenorphine in peptide-treated than in vehicle-treated buprenorphine-tolerant rats. The repeated injections of peptides did not alter the analgesic or the hyperthermic response to buprenorphine in non-tolerant rats. These studies suggest the possible role of hypothalamic peptides in blocking the development of tolerance to the pharmacological effects of buprenorphine, a potent analgesic agent.

Analgesics↗
PubMed1984

Inhibitors of an enkephalin degrading membrane-bound metalloendopeptidase: analgesic properties and effects on striatal enkephalin levels.

Intraperitoneal administration of N-[1-(R,S)-carboxy-2-phenylethyl-Phe-p-aminobenzoate, synthesized in this laboratory as a potent inhibitor of membrane-bound metalloendopeptidase (EC 3.4.24.11) caused a prolonged but weak analgesic effect on rats as measured by the tail flick test. It also caused a transitory but significant increase in striatal [Leu5]- and [Met5]enkephalin levels 3 h, after administration. Analogs of the inhibitor in which the phenylalanyl residue was replaced by an alanyl or glycyl residue also elicited prolonged analgesic responses although their inhibitory potencies were 75 and more than 1500 times lower respectively. The glycine containing derivative did not alter striatal enkephalin levels 3 h, after administration. The data suggest that inhibition of the metalloendopeptidase decreases the rate of degradation of endogenous enkephalins, however the analgesic properties of the inhibitors do not seem to be related to their inhibitory potencies. Factors other than changes in striatal enkephalin levels may contribute to the analgesic effect of the three N-carboxyphenylethyl derivatives.

4-Aminobenzoic Acid↗
PubMed1984

Is methylnalorphinium the prototype of an ideal peripheral analgesic?

Oral methylnalorphine ( methylnalorphinium ) caused a dose-dependent selective inhibition of inflammatory hyperalgesia (measured in the rat by a modified version of the Randall- Selitto test) without affecting the oedema. When subcutaneously injected, repeated doses of morphine for 5 days caused progressive analgesic tolerance. Tolerance was not observed after similar treatment with methylnalorphinium or methylmorphinium . Animals displaying analgesic tolerance to systemic morphine did not exhibit tolerance to the local ( intraplantar ) injection of morphine, methylnalorphinium or methylmorphinium . In contrast with nalorphine and other opiates, methylnalorphinium did not reduce intestinal transit in mice. Methylnalorphinium , a mixed opiate agonist-antagonist devoid of central effects, might be considered the prototype of an ideal peripheral analgesic since it was orally active, did not affect intestinal transit and did not cause analgesic tolerance.

Analgesics↗