Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANALGESICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed1992

Infusions of 6-hydroxydopamine into the nucleus accumbens abolish the analgesic effect of amphetamine but not of morphine in the formalin test.

The effects of bilateral infusions of 6-hydroxydopamine into the nucleus accumbens on analgesia produced by D-amphetamine and morphine were examined, in separate experiments, in the formalin test in rats. The lesions in the two experiments were not significantly different and dopamine in the nucleus accumbens, olfactory tubercle and striatum was depleted to 21.1%, 40.3% and 65.0% of control values, respectively. D-Amphetamine (0.75 and 2.0 mg/kg) and morphine (3.0 and 6.0 mg/kg) attenuated the response to formalin in unlesioned control rats. The analgesic effect of amphetamine was severely reduced by 6-hydroxydopamine lesions, and the residual analgesia was correlated with the amount of dopamine in the nucleus accumbens, but not with dopamine levels in the olfactory tubercle or striatum. Lesions also attenuated the locomotor stimulant effect of amphetamine. The analgesic effect of morphine was not altered by 6-hydroxydopamine infusions, nor was there any correlation between the analgesic effect of morphine and dopamine concentration in the nucleus accumbens, olfactory tubercle or striatum. The results indicate that the dopamine innervation of the nucleus accumbens is not critical for the analgesic effect of morphine but plays a major role in the analgesic effect of amphetamine.

Analgesics↗
PubMed1984

Central actions of AD-1211, an analgesic lacking common opiate features.

The site of the analgesic action of AD-1211, the less active stereoisomer, and its pharmacological features were investigated. AD-1211, as well as pentazocine and morphine, blocked the reflex hypertension caused by injection of both bradykinin and bradykinin plus PGE1 into the splenic artery of dogs. In the rat or mouse writhing test, the analgesic activity of AD-1211 after intraperitoneal and intracisternal administration was equal to and more than 40 times, respectively, that after intravenous administration. The analgesic activity of AD-1211, unlike that of pentazocine and morphine, was incompletely reversed by naloxone and was not attenuated even by its repeated administration for 7 days in the mouse writhing and tail pressure test, respectively. AD-1211, unlike pentazocine and/or morphine, lacked some effects on central nervous, respiratory and cardiovascular function in conscious animals. These results demonstrate that AD-1211 produces its analgesic action through a central mechanism but lacks some of the common pharmacological actions shown by morphine-like analgesics.

Acetates↗
PubMed1989

Dopamine D-1 and D-2 receptor antagonists potentiate analgesic and motor effects of morphine.

To examine the role of dopamine receptor subtypes mediating analgesic and motor responses to opioids, rats were pretreated with either saline or a selective D-1 or D-2 dopamine receptor antagonist 10 min prior to morphine (12 mg/kg IP). Analgesic response latency was determined using the hot plate test (52.5 degrees C and 55 degrees C), and catalepsy was assessed using the abnormal posture test. Morphine increased analgesic response latency to 44.5 +/- 7.9% of the maximum possible response, but had no cataleptic effect in the abnormal posture test. Pretreatment with either the D-1 antagonist, SCH 23390 (50-100 micrograms/kg), or the D-2 antagonist, eticlopride (20-150 micrograms/kg), potently enhanced morphine analgesia as measured on the 52.5 degrees C hot plate. Peak analgesic responses to morphine increased to 100 +/- 0% and 91.9 +/- 7.5% of maximum with the highest doses of SCH 23390 and eticlopride, respectively. These treatments also produced catalepsy. Increasing the hot plate temperature to 55 degrees C reduced response latency in groups treated with either dopamine receptor antagonist plus morphine. This indicates that the animals were capable of responding at a shorter latency and demonstrates that motor impairment cannot account for potentiation of morphine analgesia by D-1 and D-2 antagonists at 52.5 degrees C. These results show that the relationship between dopamine and opioids with respect to analgesic and motor systems involves both dopamine receptor subtypes.

Analgesics↗
PubMedDate not supplied

Supersensitivity to opioid analgesics following chronic opioid antagonist treatment: relationship to receptor selectivity.

The effect of chronic opioid antagonist treatment on the analgesic potency of six opioid agonists was compared to changes in opioid receptor density and the selectivity of each agonist for mu (DAMGO), delta (DPDPE) and kappa (U69,593) opioid receptors. Mice were implanted SC with a 15-mg naltrexone or placebo pellet for 8 days. The pellets were removed and 24 h later, mice were sacrificed and binding studies were conducted, or mice were tested in analgesia (tail-flick) dose-response studies. All six analgesics acted as full agonists for both placebo and naltrexone-treated mice. Naltrexone increased the analgesic potency of methadone, etorphine, fentanyl, meperidine, and oxycodone by 1.9-3.2-fold. The analgesic potency of propoxyphene was not increased significantly (1.3-fold). In saturation binding studies in brain homogenate, naltrexone increased the Bmax of mu, delta, and kappa opioid receptors by 86, 43, and 33%, respectively, without altering Kd. Competition binding studies for each receptor type were conducted in brains from untreated mice, and KIs were determined for each agonist. All agonists had greatest selectivity toward mu compared with delta and kappa receptors. There did not appear to be an obvious relationship between receptor selectivity and the magnitude of supersensitivity. These studies indicate that supersensitivity occurs for a broad range of opioid analgesics following chronic opioid antagonist treatment in the mouse. However, the selectivity of these agonists for mu, delta, and kappa receptors does not appear to correlate with differences in supersensitivity.

Analgesics↗
PubMed1980

A method for evaluating analgesic agents in rats.

A method is described for evaluating antinociceptive activity in rats using writhing responses induced by 4% sodium chloride solution. Narcotic and nonnarcotic analgesics, narcotic antagonists except naloxone, and antipyretic and nonsteroidal antiinflammatory drugs were effectively evaluated at relatively low doses using this method. Parenteral ED50 values of these compounds ran parallel to their clinical doses. The method detected not only the analgesic action of the above drugs but also that of methamphetamine. In spite of its high sensitivity, the method was specific in the sense that CNS-depressant, muscle relaxant, anticholinergic, and antihistamine drugs and anesthetics were inactive even at toxic doses. On the other hand, the decrease in the analgesic activity of morphine upon chronic injection was also observed with this method. The writhing test with 4% sodium chloride in rats was concluded to be a sensitive and specific test for analgesic drugs and useful for examining changes in analgesic activity of drugs during chronic administration.

Acetates↗
PubMedDate not supplied

Derivatives of beta-casomorphins with high analgesic potency.

Beta-casomorphin (5) Tyr-Pro-Phe-Pro-Gly, a partial sequence of bovine beta-casein with moderate opioid properties and mu-receptor affinity, was modified by substituting for the natural L-amino acids their D-analogs, and D-pipecolic acid, as well as by amidation of the C-terminal. Substitution of D-Pro or D-pipecolic acid for L-Pro4 considerably increased the analgesic action and the potency on guinea-pig ileum of beta-casomorphin (5) as well as of casomorphin [4] amide. The resulting D-Pro4 analogs Deprolorphin and Deproceptin which showed high analgesic potency after both intracerebroventricular and intravenous administrations. Also, the substitution of D-Phe for L-Phe3 enhanced, even though to a lesser degree, the antinociceptive action. Both naltrexone and naloxone completely blocked the effects in vivo and in vitro. The substitution of D-Pro for L-Pro2 abolished the opioid-like actions, while substituting D-pipecolic acid for L-Pro2 resulted in an increased analgesic effect of remarkably long duration. The correlation of analgesic action with the effects on isolated organs separates the L-Pro4-substituted derivatives and D-Phe3-CM(5) from the other modified casomorphins and morphine, indicating that the analgesic potency of the former was about ten times that of the latter group in the case of identical GPI-potency. This may involve different subpopulations of opiate mu-receptors.

Amino Acid Sequence↗
PubMed1987

Psychological factors influencing post-operative pain and analgesic consumption.

The personality factors, post-operative pain experience and analgesic requirements after minor oral surgery under general anaesthesia of 103 patients are presented. Psychiatric morbidity, neuroticism and anxiety were related to increased pain which tended to persist longer than normal. Trait anxiety also correlated with simple analgesic consumption, and neuroticism was weakly associated with Omnopon requirements. Thus, regular analgesics prescribed for at least 3 days will anticipate the needs of such patients. Despite higher levels of anxiety and neuroticism, women did not complain of more pain or require more analgesia than men in this study. There was also no overall correlation between post-operative pain experience and analgesic requirements. Therefore analgesic tablet consumption cannot be used as a measure of pain control.

Adolescent↗
PubMed1986

Analgesic sensitivity of two post-partum pain models.

Post-partum uterine cramping and episiotomy pain are established, frequently used, clinical pain models for efficacy trials of investigational new analgesic agents. To determine the respective assay sensitivity of these two models in assessing relative efficacy, we reviewed data from 6 phase II, randomized, stratified, parallel, placebo-controlled, double-blind, single-dose studies involving hospitalized women with moderate or severe post-partum uterine cramping (332 patients) or episiotomy pain (434 patients). Using subjective reports as indices of response, patients rated pain intensity and relief at periodic interviews for 6-7 h. Post-partum uterine cramping showed excellent assay sensitivity for detecting differences among peripherally acting analgesics. In the same clinical trial this model could discriminate between a new drug and aspirin 650 mg, a standard reference analgesic, and between 2 graded doses of the new active agent (i.e., good upside sensitivity). In addition the uterine cramp model showed separation between placebo and all active agents (i.e., good downside sensitivity). Episiotomy pain demonstrated similar upside and downside discrimination in clinical trials of several weak centrally acting drugs. These data suggest that post-partum cramping is an excellent pain model for analgesic investigation of new non-steroidal anti-inflammatory drugs, and episiotomy pain for new weak narcotic and opioid analgesics.

Analgesics↗
PubMed1994

Conditioned place preference paradigm: a novel approach for analgesic drug assessment against chronic pain.

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.

Analgesics↗
PubMed1990

Analgesic effects of diltiazem and verapamil after central and peripheral administration in the hot-plate test.

1. The analgesic effects of diltiazem and verapamil, both per se and together with morphine, were studied using subcutaneous (s.c.) and intracerebroventricular (i.c.v.) administrations, in the hot-plate test in mice. 2. The i.c.v. injection of verapamil (15-120 micrograms/mouse) and diltiazem (60-120 micrograms/mouse) induced dose-dependent analgesic effects. 3. The i.c.v. administration of verapamil (30-120 micrograms/mouse) and diltiazem (60-120 micrograms/mouse) significantly enhanced, in a dose-dependent way, the analgesic effects of morphine and produced a parallel displacement to the left of the morphine log dose-response line. 4. When these calcium channel blockers were administered subcutaneously at doses of 40 and 80 mg/kg, they exerted no analgesic actions, but dose-dependently potentiated the analgesic effects of morphine, producing a parallel shift to the left of the morphine log dose-response line. 5. These results suggest that inhibition of calcium entry through calcium channels induced by verapamil and diltiazem may play a role in analgesia development.

Analgesics↗
PubMed1987

Benefit-risk ratio of agonist-antagonist analgesics.

Many agonist-antagonist analgesic substitutes for morphine have been synthesized and their safety and efficacy evaluated in animals, humans or both. Several drugs in this class have achieved regulatory approval and have reached the marketplace. Agonist-antagonist analgesics have proved clinically acceptable and are in some respects superior to the standard narcotic analgesics, most markedly in their diminished addiction liability. In other respects, however, agonist-antagonist analgesics are inferior to morphine; they probably have lower analgesic ceiling efficacy, are more likely to produce psychotomimetic effects, and can precipitate abstinence in patients physically dependent on opioids.

Analgesics, Opioid↗
PubMed1991

Studies on the constituents of Aconitum species. IX. The pharmacological properties of pyro-type aconitine alkaloids, components of processed aconite powder 'kako-bushi-matsu': analgesic, antiinflammatory and acute toxic activities.

Eight pyro-type aconitine alkaloids contained in the processed aconite powder 'Kako-bushi-matsu' were studied for their analgesic, antiinflammatory and acute toxic actions. All these compounds showed significant analgesic and antiinflammatory actions. Among the pyro-type alkaloids, 16-epi-pyrojesaconitine and pyrojesaconitine were the most potent analgesics. The analgesic activity of pyro-type aconitine alkaloids was lower than that of each of the parent alkaloids, aconitine, mesaconitine, hypaconitine and jesaconitine. However, pyro-type aconitine alkaloids had very low toxicity, and the decreasing rates of the toxicity in changing from the parent alkaloids to the pyro-type aconitine alkaloids were much larger than those relating to the analgesic activity. Eight pyro-type aconitine alkaloids were found to inhibit the carrageenin-induced hind paw edema at 2 to 6 h after the carrageenin subplantar injection. Consequently, it was demonstrated that the pyro-type aconitine alkaloids produced through the processing of raw aconite roots, 'Bushi', have a role in the medicinal effects of the processed aconite powder 'Kako-bushi-matsu'.

Aconitine↗
PubMed1991

Myrcene mimics the peripheral analgesic activity of lemongrass tea.

Oral administration of an infusion of lemongrass (Cymbopogon citratus) fresh leaves to rats produced a dose-dependent analgesia for the hyperalgesia induced by subplantar injections of either carrageenin or prostaglandin E2, but did not affect that induced by dibutyryl cyclic AMP. These results indicate a peripheral site of action which was confirmed with the essential oil obtained by steam distillation of the leaves. Silica gel column fractionation of the essential oil allowed the identification of myrcene as the major analgesic component in the oil. Identification of the components was made by thin-layer chromatography and checked by mass spectrometry. The peripheral analgesic effect of myrcene was confirmed by testing a standard commercial preparation on the hyperalgesia induced by prostaglandin in the rat paw test and upon the contortions induced by intraperitoneal injections of iloprost in mice. In contrast to the central analgesic effect of morphine, myrcene did not cause tolerance on repeated injection in rats. This analgesic activity supports the use of lemongrass tea as a "sedative" in folk medicine. Terpenes such as myrcene may constitute a lead for the development of new peripheral analgesics with a profile of action different from that of the aspirin-like drugs.

Acyclic Monoterpenes↗
PubMed1994

Postoperative analgesics for children and adolescents: prescription and administration.

Pain was measured and analgesic treatment examined in 131 children and adolescents, 8-17 years of age, for 5 days after surgery. Analgesic data were converted to 10 mg intramuscular morphine-equivalent doses (IMMSEQ) and were designated appropriate or inappropriate for body weight. Analgesic onset, peak, and duration were calculated in relation to administration routes and the time pain assessments were made. Children reported moderately severe pain in many body locations. Initially, all but two children were prescribed and ultimately all but one received analgesics. Prescribed and administered doses were frequently less than doses recommended for weight. Two-thirds of the children were beyond analgesic action when pain was assessed. Weak to moderately strong associations were noted between IMMSEQ doses and pain intensity scores on each of the 5 postoperative days. Unfortunately, findings indicate that children continue to be undertreated when they experience postoperative pain.

Adolescent↗
PubMed2004

Mandated pain scales improve frequency of ED analgesic administration.

A retrospective study design was used to determine the effect of introducing a mandated verbal numeric pain scale on the incidence and timing of analgesic administration in the ED. Consecutive patients presenting with renal colic, extremity trauma, headache, ophthalmologic trauma, and soft tissue injury were included. 521 encounters were reviewed before and 479 encounters after the introduction of the pain scale. Groups were similar in baseline characteristics. Analgesic use increased from 25% to 36% (p < 0.001), and analgesics were administered more rapidly after the scale was introduced (113 minutes vs. 152 minutes, p = 0.09). Analgesic use correlated with pain severity. Patients undergoing diagnostic testing were less likely to receive analgesics, especially when presenting with a headache (p < 0.001). We conclude that use of a pain scale at triage significantly increases use of analgesia, and shortens the time till its administration. Patients undergoing diagnostic workups were less likely to receive analgesia.

Adult↗
PubMed2005

Analgesic effect of intra-articular tramadol compared with morphine after arthroscopic knee surgery.

PURPOSE: The aim of the study was to compare the analgesic effect of 5 mg intra-articular (IA) morphine with 50 mg IA tramadol. TYPE OF STUDY: Prospective double-blind randomized trial. METHODS: Seventy-five patients having elective arthroscopic surgery of the knee were randomized to receive IA tramadol 50 mg (tramadol group), IA morphine 5 mg (morphine group), or IA normal saline (control group), in equivalent volumes (20 mL). The tourniquet was released 10 minutes after analgesic administration. Verbal pain rating score between 0 and 10 (VRS), supplemental analgesic requirements, and incidence of side effects were recorded postoperatively. RESULTS: Results are given as (median [5-95 percentiles]). The control group had a significantly shorter time to first analgesic request (25 min [15-55]) than morphine group, (34 min [15-158], P < .008) and the tramadol group, (33 min [17-728], P < .008). The patients in the control group complained of more severe pain (VRS 7 [4-10]) when they arrived at the postanesthesia care unit compared with the morphine group (VRS 1 [0-9], P = .002) and with the tramadol group (VRS 0 [0-9], P = .002). These treatment benefits were especially prominent in the patients who had meniscectomy or in the subgroup of patients with more than 6 months of preoperative pain. There was no statistical difference between the tramadol and morphine groups in the time to first analgesia, postoperative pain scores after arrival at the postanesthesia care unit, consumption of rescue analgesic, or side effects. CONCLUSIONS: We conclude that 50 mg IA tramadol provides analgesia equivalent to 5 mg IA morphine. LEVEL OF EVIDENCE: Level II, randomized controlled trial that shows no significant difference and lacks narrow confidence intervals.

Adult↗
PubMed2006

Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism.

OBJECTIVES: Preclinical studies have suggested that the mechanism of the analgesic action of acetaminophen (INN, paracetamol) is linked to the serotonergic system and that it is inhibited by tropisetron, a 5-hydroxytryptamine type 3 antagonist. The aim of this study was to confirm these findings in humans. METHODS: Twenty-six rapid metabolizers of tropisetron were included in this double-blind crossover study. After ethical approval, at weekly intervals, the subjects took a single oral dose of 1 g acetaminophen combined with either intravenous tropisetron (5 mg), granisetron (3 mg), or placebo (saline solution). For each session, the analgesic effect of acetaminophen was assessed by use of a pain self-evaluation instrument, the Pain Matcher. The pain detection threshold was determined 5 times over the period of the 4 postdosing hours. The area under the curve (0-4 hours) (mean +/- SD) of acetaminophen/tropisetron and the area under the curve of acetaminophen/granisetron were compared with the effect of acetaminophen/placebo. Blood samples for acetaminophen concentration measurements were taken to evaluate a pharmacokinetic interaction. RESULTS: The analgesic effect of acetaminophen/placebo (expressed as the area under the curve of the percentage of the individual pain score reported at baseline along time [% x min]) (2145 +/- 2901 % x min) was totally inhibited by both tropisetron (89 +/- 1747 % x min, P = .007) and granisetron (45 +/- 2020 % x min, P = .002). Acetaminophen concentration was not significantly different when associated with tropisetron (P = .919) or granisetron (P = .309). CONCLUSION: These results clearly show for the first time in humans that the coadministration of tropisetron or granisetron with acetaminophen completely blocks the analgesic effect of acetaminophen. They support the hypothesis that the mechanism of the analgesic action of acetaminophen might involve the serotonergic system. Furthermore, they demonstrate a pharmacodynamic interaction between these 2 types of drugs, which are frequently coadministered, especially in cancer patients.

Acetaminophen↗
PubMed2004

Broad analgesic profile of buprenorphine in rodent models of acute and chronic pain.

Buprenorphine is a potent opioid analgesic clinically used to treat moderate to severe pain. The present study assessed its analgesic efficacy in a broad range of rodent models of acute and chronic pain. In the phenylquinone writhing, hot plate, and tail flick mouse models of acute pain, full analgesic efficacy was obtained (ED50 values: 0.0084-0.16 mg/kg i.v.). Full analgesic efficacy was also obtained in yeast- and formalin-induced inflammatory pain (ED50 values: 0.0024-0.025 mg/kg i.v., rats and mice) and in mustard-oil-induced spontaneous pain, referred allodynia, and referred hyperalgesia in mice (ED50 values: 0.018-0.025 mg/kg i.v.). Buprenorphine strongly inhibited mechanical and cold allodynia in mononeuropathic rats, as well as mechanical hyperalgesia and cold allodynia in polyneuropathic rats (ED50 values: 0.055 and 0.036 mg/kg i.v. and 0.129 and 0.038 mg/kg i.p., respectively). It is concluded that buprenorphine shows a broad analgesic profile and offers the opportunity to treat different pain conditions, including neuropathic pain.

Acute Disease↗