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PubMed1990

Dual action mechanisms of KK-3, a newly synthesized leu-enkephalin derivative, in the production of spinal analgesic effects.

The action mechanism for the production of spinal analgesia of KK-3, tyrosyl-N-methyl-gamma-aminobutylyl-phenylalaninol, was examined by the tail pinch and tail flick methods. Intrathecal KK-3, 2.5, 5 and 10 nmol/mouse, dose-dependently produced an analgesic effect in both methods. In the tail pinch method, the analgesia was suppressed by 2 mg/kg but not by 1 mg/kg of naloxone; however, the analgesic effect was significantly antagonized by 1 and 2 mg/kg Mr2266, a kappa-antagonist. Meanwhile, both naloxone and Mr2266 failed to block the analgesic effect of KK-3 in the tail flick test. Intrathecal capsaicin, 0.3, 3 and 15 nmol/mouse, also produced a dose-dependent analgesic effect in the tail flick test, whereas no appreciable analgesia could be found in the tail pinch test. Neither naloxone nor Mr2266 blocked the analgesic effect of capsaicin. The results indicate that KK-3 may possess two separate pharmacological mechanisms for the production of analgesic effects on the spinal level: one is the depletion of substance P following its release from the spinal cord, and the other is the mediation through kappa-opioid receptors.

Analgesics↗
PubMed2005

Activation of spinal anti-analgesic system following electroacupuncture stimulation in rats.

We evaluated the interaction between electroacupuncture (EA)-induced antinociception and an endogenous anti-analgesic system. EA was applied to the ST-36 acupoint for 45 min in male Sprague-Dawley rats, and pain thresholds were assessed by the hind-paw pressure test. EA produced a marked increase in pain thresholds and its antinociceptive action was completely reversed by naloxone (5 mg/kg). The analgesic effects of subcutaneous morphine (7 mg/kg) following EA stimulation were significantly attenuated. The attenuation of morphine analgesia was inversely proportional to the time intervals between EA termination and morphine injection, and the effect was not observed 120 min after EA stimulation. The analgesic effects of i.t. morphine (10 microg), but not i.c.v. morphine (25 microg), following EA were also attenuated. On the other hand, systemic morphine (7 mg/kg)-induced hyperthermia was not affected by EA. Moreover, i.c.v. morphine, but not i.t. morphine, produced hyperthermia. The i.c.v. morphine-induced hyperthermia was not affected by EA, similar to i.c.v. morphine analgesia. These results suggest that the attenuation of morphine analgesia following EA, that is, the activation of an endogenous anti-analgesic system, is closely related to the activation of an analgesic system by EA and that the spinal cord plays a critical role in the activation of the endogenous anti-analgesic systems.

Analgesia↗
PubMed2001

Opioid analgesics versus ketorolac in spine and joint procedures: impact on healthcare resources.

BACKGROUND: Ketorolac's efficacy as a postoperative analgesic has been shown to be comparable to that of narcotic analgesics, but with significantly fewer narcotic-related adverse events. OBJECTIVE: To assess whether the choice of postoperative analgesic, narcotic or ketorolac, has an impact on healthcare resource utilization and cost durng inpatients' recovery period. DESIGN: Retrospective, multicenter, controlled, parallel, cost-minimization analysis. SETTING: Six US teaching hospitals. PATIENTS: This study included 559 patients that underwent either a spine or joint procedure and received adequate doses of narcotic (n = 284 of either morphine or meperidine) or ketorolac (n = 275). MEASUREMENTS: Time to reach recovery milestones, average utilization of healthcare resources, and average per-case postoperative treatment cost. RESULTS: Several recovery milestones, including time to first bowel movement, first oral intake, and first unassisted ambulation, were reached sooner in the ketorolac group, with a resultant shorter mean length of postoperative stay (narcotic 3.78 d, ketorolac 2.80 d; p = 0.01). Total per-patient cost of treatment was 32% greater in the narcotic group, resulting primarily from higher costs associated with hospitalization. CONCLUSIONS: Despite the higher acquisition cost of medication, healthcare resource utilization and total per-patient cost of treatment were lower for patients in the ketorolac group compared with patients in the narcotic analgesic study group. The majority of patients in the ketorolac group were also given concurrent narcotic analgesics; therefore, the beneficial effects observed may be secondary to the combination of ketorolac and narcotic analgesics.

Analgesics, Opioid↗
PubMed2003

Analgesic efficacy of calcitonin for vertebral fracture pain.

OBJECTIVE: To evaluate the analgesic efficacy of calcitonin for treating the pain of vertebral fractures associated with osteoporosis. DATA SOURCES: Searches of MEDLINE (1966-July 2002), Cochrane Library, International Pharmaceutical Abstracts (1977-July 2002), and an extensive manual review of journals were performed using the key search terms calcitonin, analgesic, osteoporosis, vertebral fracture, and pain. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for this review. DATA SYNTHESIS: Fractures, especially vertebral fractures, are a common complication of osteoporosis, leading to significant pain. Calcitonin has been studied for its analgesic properties. Fourteen double-blind, placebo-controlled trials that evaluated the analgesic efficacy of calcitonin for osteoporosis-related vertebral fracture pain were identified and reviewed. Thirteen of these studies demonstrated statistically significant improvement in pain or function in calcitonin-treated patients. CONCLUSIONS: Calcitonin has proven efficacy in acute pain associated with osteoporosis-related vertebral fractures. Analgesic effects are seen with intranasal, parenteral, and rectal administration. Future studies comparing calcitonin with other commonly used analgesics are needed to more clearly define its place in therapy.

Analgesics↗
PubMed2004

Television and adolescent use of over-the-counter analgesic agents.

BACKGROUND: Portrayals of the use of over-the-counter (OTC) analgesics on television may stimulate their use. OBJECTIVE: To explore the association between taking OTC analgesics and television viewing by adolescents. METHODS: A standardized self-administered questionnaire among first-year (mean age 13.16 y) and fourth-year (mean age 16.37 y) secondary students in Flanders, Belgium (n = 2546) was administered in a school setting. The independent variable was television viewing; control variables were school year, gender, drinking alcohol, days off sick, computer gaming, and Internet use. The main outcome variable was monthly use of OTC analgesics. RESULTS: On average, respondents watched 3 hours 18 minutes of television per day (boys more than girls, first-year students more than fourth-year students). Per additional hour of television per day, the odds that respondents were regular users of analgesics were 1.16 times higher (95% CI 1.08 to 1.24). For the 10% heaviest viewers, the odds were 2.30 times higher (95% CI 1.25 to 4.24) compared with the 10% lightest viewers. Odds of OTC analgesic use were higher for students reporting more sick days in the past year (OR 1.38, 95% CI 1.28 to 1.49), regular users of alcohol (OR 1.33, 95% CI 1.17 to 1.50), and girls (OR 1.92, 95% CI 1.35 to 2.73). CONCLUSIONS: A relationship was found between watching television and the use of OTC analgesics, even after controlling for gender and lifestyle measures. More research is needed to establish whether this relationship is causal.

Adolescent↗
PubMed2005

Characteristics of pain and response to analgesic treatment in dogs and cats examined at a veterinary teaching hospital emergency service.

OBJECTIVE: To estimate the prevalence and characteristics of pain in dogs and cats examined by an emergency service at a veterinary teaching hospital and evaluate the response of dogs and cats with signs of pain to analgesic treatment. DESIGN: Cross-sectional study. ANIMALS: 317 dogs and 112 cats. PROCEDURE: A questionnaire was used to categorize the characteristics of pain. The location, cause, and signs of pain were determined by obtaining a thorough history and conducting a physical examination. Pain was categorized by type (superficial somatic, deep somatic, or visceral), mechanism (inflammatory, neuropathic, or both), severity (mild, moderate, or severe), and duration. Evidence for primary or secondary hypersensitivity and hyposensitivity to manipulation was determined. The response to single or multiple analgesic drug administration was assessed. RESULTS: 179 (56%) dogs and 60 (54%) cats had signs of pain. In most of these dogs and cats, pain was classified as acute (< 24 hours' duration) and of moderate severity and was associated with primary hypersensitivity. Most dogs had deep somatic pain; most cats had visceral pain. Inflammation was the most common mechanism. One hundred nineteen (66%) dogs and 41 (68%) cats were treated with analgesic drugs. Analgesic treatment was considered effective in 73 (61%) dogs and 31 (76%) cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that moderate to severe acute somatic pain caused by inflammation is common in dogs and cats examined by an emergency service and that a combination of multiple analgesic drugs is more effective than any single analgesic drug in the treatment of pain in these dogs and cats.

Analgesics↗
PubMed2005

Use of web-based data collection to evaluate analgesic administration and the decision for surgery in horses with colic.

REASONS FOR PERFORMING STUDY: There is no current veterinary information with regard to data entry on a website. We therefore completed a prospective study on use of analgesics in relation to the need for abdominal surgery using a web-based survey instrument. OBJECTIVES: To establish an internet-based data entry system that could be used to record prospective data on horses with colic. HYPOTHESIS: Failure of horses to respond to the initial administration of an analgesic is an indicator of the need for abdominal surgery. METHODS: A survey was developed to determine if the response to administration of an analgesic during a veterinarian's first examination of a horse with colic was related to the need for surgery. Veterinarians were contacted via AAEP and ECN listservs requesting submission of cases using a log-in system at a data entry website. The survey was completed by submission of a data entry page. RESULTS: Twenty-seven veterinarians submitted details of 119 cases of colic, 28 of which required surgery. The need for surgery was significantly associated with moderate or severe pain observed during the first examination compared to mild or no pain, and with constant pain or return of pain after administration of one or more analgesics and the need to administer a second analgesic treatment. Abnormal findings on rectal examination were not associated with the need for surgery, whereas total absence or decrease of intestinal sounds was significantly related to the odds that surgery was needed. The web-based data collection was successful in collecting all data points on the survey for each case. CONCLUSIONS: This study reinforced veterinarians' use of response to therapy as a way to determine the need for abdominal surgery. POTENTIAL RELEVANCE: When a specific diagnosis has not been made, lack of response or resumption of colic after analgesic administration should be considered as an indicator of the need for surgery. Web-based collection of data allows veterinary practitioners to participate in clinical research by providing prospective data.

Analgesics↗
PubMed1999

1',1'-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties.

1',1'-Dimethylheptyl-Delta-8-tetrahydrocannabinol-11-oic acid (CT-3) is a novel cannabinoid that is under development by Atlantic Pharmaceuticals as an anti-inflammatory and analgesic drug. The objective of the study was to investigate the effects of CT-3 on overt symptom complex (Irwin's test), nociception, gastrointestinal (GI) ulceration, and pharmacological availability after intragastric (i.g.) and intraperitoneal (i.p.) administration. Analgesic studies were assessed in the hot-plate (55 degrees C) and the tail clip tests in mice and in the tail clip test in rats. In addition, pharmacological interaction of CT-3 with the solvent dimethyl sulfoxide (DMSO) was investigated in rats. In mice, CT-3 decreased spontaneous motor activity and induced dose-dependent, analgesic activity in the tail clip and hot-plate tests, with potency similar to morphine sulfate after i.g. and i.p. administration. However CT-3 showed more prolonged duration of analgesic action than morphine. In rats, CT-3 showed marked analgesia in the tail clip test and had similar i.p. and i.g. median effective dose (ED(50) values; 5 mg/kg). CT-3 was devoid of GI ulceration when administered with DMSO either acutely at doses below 100 mg/kg or chronically at a dosage of 30 mg/kg/day for 5 days. In contrast, indomethacin induced GI ulceration and deaths. The concurrent use of DMSO with CT-3 decreased its analgesic action, increased its adverse central nervous system effects, and induced GI ulceration. The evidence indicates that CT-3 exhibits a large dissociation between its anti-inflammatory/analgesic effects and its ulcerogenic actions. CT-3 warrants clinical development as a novel anti-inflammatory and analgesic drug.

Administration, Oral↗
PubMed2000

[Metamizol--a new effective analgesic with a long history. Overview of its pharmacology and clinical use].

Metamizol is an effective, non-opioid analgesics which was originally introduced to the therapy in the year 1922. However, with the reference to the side effects of other related pyrazolone derivatives its administration, similarly as the usage of other pyrazolones, was significantly limited. Later, metamizol has been used, usually mixed, with spasmolytic agents and quite recently it has been introduced as a mono-component medicament. Metamizol proved to be a very effective analgesic. When administered in equipotent doses, it had its effects comparable to various opioid analgesics, such as tramadol, pentazocine and pethidine. Beside the strong analgesic effect, it produces also significant antipyretic and splasmolytic effects without the adverse, unpleasant anticholinergic impact. Its spasmolytic effect on the smooth muscle of the sphincter Oddi, urinary tract, and the gal bladder is comparable to the effects of buthylscopolamine. Unlike aspirin and other nonsteroidal antiinflammatory drugs it has, however, no antiinflammatory activity when administered in clinical doses. Similarly, metamizol has no effect on the CNS, cardiovascular system, renal and metabolic functions. On the other hand, metamizol, like aspirin, has got a significant effect on the aggregation of platelets. Metamizol is basically a prodrug. The parent substance is not effective before its conversion into two active metabolites (4-methylaninoantipyrine and 4-aminoantipyrine) in the body. Metamizol is well absorbed from the small intestine but only two above mentioned active metabolites and no parent drug can be detected in the blood. The active metabolites are consequently metabolised to ineffective metabolites including the relevant acetylderivatives, in which the acetylation phenotypes can be distinguished. In the therapy, metamizol can be used, as an analgesic, at post-surgical pain, patient's controlled analgesia (PCA), at the cancer's pain and in the pains of different origin (post-traumatic pain, the pain at myocardial infarction, craniocerebral trauma, and the invasive diagnostic interventions), as well as at he pain of neuromuscular origin, headache and migraine. Its spasmolytic effect in connection with a strong analgesic activity is very useful at various colic attacks. Further, metamizol is a useful antipyretic both in the adults and children. Its adverse effects are not pronounced and drug interactions are minimal. Only when metamizol is administered together with cyclosporine, the blood levels of the last substance should be regularly checked.

Analgesics↗
PubMed1975

[Analgesic nephropathy].

Analgesic nephropathy is characterized by poor clinical symptoms. Abnormal urinary findings are rare. The disease is usually discovered if advanced renal damage has occurred with elevated serum creatinine, papillary necrosis, microhematuria and renal colics. There is abundant evidence, that abuse of phenacetin leads to analgesic nephropathy. Aspirin may have only an additive effect with phenacetin in causing renal damage. The primary medullary changes caused by phenacetin or one o f its metabolites are: Interstitial fibrosis, thickening of tubular basement membrane, loss of tubular epithelium and finally destruction of the loops of Henle. The consequence of these histological changes is a loss of urinary concentrating ability, one of the earliest findings in analgesic nephropathy. Inflammatory cell infiltration and involvement of the renal cortex with corresponding functional defects are secondary. Intravenous pyelography reveals in this stage of the disease symmetrically shrunken kidneys with a smooth wavy outline, whereby in contrast to the pyelonephritic changes the prtrusions correspond with the renal calyces. Papillary necrosis with the typical "halo shacow" in the pyelogramm rarely leads to the discovery of the disease.--Cessation of phenacetin consumption is usually associated with stabilization of renal funciton in patients with serum creatinine levels below 1.5 mg percent; with elevated serum creatinine there is a slow progression of the disease.--Analgesic nephropathy may be prevented by high fluid intake and avoidance of more than 150 g phenacetin per year respectively 0.5 g per day. Coffein, a constituent of many preparations, has a protective effect only with sufficient fluid intake.--The socio-economic importance of the analgesic nephropathy is given by the fact, that in the German Federal Republic 10 percent and in Australia even 20 percent of the patients requiring recurrent dialysis suffer from analgesic nephropathy. The following measures have been found to be effective in order to reduce phenacetin abuse: 1. Preparations containing phenacetin subject to prescription. 2. No advertising in newspapers and television. 3. Detailed information about kidney damaging effect of phenacetin on each packaging.

Acidosis, Renal Tubular↗
PubMed2001

[Control of postoperative pain in heart surgery. Comparison of analgesics].

BACKGROUND: Evaluation of the efficacy of three analgesic drugs (tramadol, ketorolac, and morphine) for the control of postoperative pain in cardiac surgery. METHODS DESIGN: prospective randomized study. SETTING: University Hospital, Postoperative intensive care unit. PARTICIPANTS AND INTERVENTION: sixty patients, who underwent cardiac surgery, were studied. They were randomly allocated in four groups, treated with a different postoperative analgesic therapy: A) tramadol in continuous infusion; B) ketorolac in continuous infusion; C) tramadol, in repeated boluses; D) morphine, in repeated boluses. MEASUREMENTS: the analgesic efficacy of each drug and administration protocol was evaluated by hemodynamic stability, arterial blood gases analysis, Visual Analogue Scale (VAS), resting and after cough, the VAS derivatives PID and SPID, the concentration of plasma epinephrine and norepinephrine, at eight postoperative times. Adverse effects were also registered. RESULTS: Only tramadol, in continuous i.v. infusion, achieves the required analgesic effect, significantly decreasing both VAS scores, at the end of the administration of the drug. This treatment reduced epinephrine plasma levels in the first postoperative day, when the residual analgesic effect of surgical anesthesia can be considered disappeared. CONCLUSIONS: Tramadol in continuous infusion (dose 12 mg/h) proved to be effective for the control of postoperative pain after cardiac surgery. The proposed dose represents a good compromise between analgesic efficacy and interference with the vital functions of operated patients.

Adult↗
PubMed2001

Testing and comparison of non-opioid analgesics in amphibians.

Because of the lack of information about effective analgesics in non-mammalian vertebrates, the potency of various non-opioid agents were tested in a model of analgesia by using Northern grass frogs (Rana pipiens). This alternative model has been used widely for investigating opioid analgesic action. Potential non-opioid analgesics tested included antipsychotic, benzodiazepine, barbiturate, antihistamine, non-steroidal anti-inflammatory (NSAID), and partial opioid agents. Northern grass frogs were acclimated to lab conditions in individual cages. Drugs were administered systemically through the dorsal lymph sac, and analgesic effects were estimated by using the acetic acid test (AAT). The AAT is done by placing logarithmic dilutions of acid dropwise on the dorsum of the animal's thigh until a wiping response is obtained. At various doses, chlorpromazine and haloperidol (antipsychotics), chlordiazepoxide (a benzodiazepine), buprenorphine (a partial opioid agonist), and diphenhydramine (a histamine antagonist) produced moderate to strong analgesic effects. Indomethacin and ketorolac (NSAIDs), butorphanol (a partial opioid agonist), and pentobarbital (a barbiturate) produced weaker but noticeable analgesic effects. Our results are the first to document the effectiveness of a wide array of pharmacologically active agents in a novel amphibian model for analgesia. These findings provide needed data regarding the use of alternative, non-opioid agents for the treatment of pain in amphibians and other poikilothermic species.

Analgesia↗
PubMed1998

[Study on 102 cases of anorectal post-operational pain treated by long-acting analgesic].

OBJECTIVE: To observe the clinical effect and experimental result of long-acting analgesic in the treatment of anorectal post-operational pain. METHODS: Analysing the pathological features of anorectal post-operational pain, and select the Radix Stephana Tetrandra, which could disperse pathogenic Wind and dampness, relieve spasm and pain, as the major component. The authors extracted Sinomenine from the Stephana and by mixing with methylene blue and bupivacaine hydrochloride, an injection was prepared. Three groups were in the clinical observation: Long-acting analgesic group (102 cases), routine treatment group (80 cases) and the control group treated by Tramal (30 cases). The curative effect was observed and animal experiment was conducted. RESULTS: The total analgesic rate of the long-acting analgesia was 56.86%. The clinical effect was better than using Bupivacaini hydrochloride or Tramal alone (P < 0.05). It was shown in experiment that long-acting analgesic had obvious effects of topical analgesic and muscle relaxant. CONCLUSIONS: Long-acting analgesic has significant effect in relieving the anorectal post-operational pain.

Adult↗
PubMed2001

Anti-inflammatory and analgesic activity of Indian Hypericum perforatum L.

A standardised 50% aqueous ethanolic extract of the Indian variety of Hypericum perforatum (IHp) was examined for its putative anti-inflammatory and analgesic activity at the doses of 100 and 200 mg/kg, po. The experimental paradigms used were carrageenan induced pedal edema and cotton pellet induced granuloma for anti-inflammatory activity, whereas the tail flick, hot plate and acetic acid induced writhing methods were used to asses analgesic activity. Indomethacin (20 mg/kg, ip) was used as the standard anti-inflammatory drug. Pentazocine (10 mg/kg, ip) and aspirin (25 mg/kg, ip), both clinically used analgesics, were used as standard analgesics for comparison. IHp extract showed significant anti-inflammatory and analgesic activity at both dose levels, in all the paradigms used. Additionally, IHp potentiated the anti-inflammatory activity of indomethacin and analgesic activities of pentazocine and aspirin.

Analgesics↗
PubMed1999

Tramadol drops in children: analgesic efficacy, lack of respiratory effects, and normal recovery times.

Tramadol hydrochloride is a racemic mixture of two enantiomers. It has analgesic activity suitable for mild to moderate pain, part of its analgesic activity being modulated via mu receptors. Adult studies have raised the question of increased electroencephalographic activity. The study examined the analgesic efficacy, respiratory effects, and behavior plus recovery-influencing properties of tramadol in the pediatric patient. Day-case dental extraction children, aged 4-7 years having 6 or more extractions, were studied. Tramadol drops, 3 mg/kg, plus oral midazolam, 0.5 mg/kg, were administered 30 minutes prior to a sevoflurane in N2O and O2 anesthetic. Forty children received this premedication treatment (T) and 10 entered a placebo control group (P), where no tramadol was administered. Entry was random, double blind, and parallel. Analgesic efficacy was measured using the Oucher face pain scale (OFPS), with responders scoring three or less. Respiration was measured by rate and oxygen saturation. Behavior and ease of mask induction were assessed on a 4-point scale. Recovery was measured with the Aldrete scale. Parameters were measured from 30 minute preanesthetic to 120 minute postanesthetic. Analgesic efficacy was shown, with an OFPS score of 11.42 (SD 18.66) (T) and 29.80 (SD 25.14) (P) (P < .05). Responders on tramadol were 77.5% versus 0% on placebo (P < .05). No respiratory depression was seen; rates and oxygen saturations were the same preanesthetic and postanesthetic. Similarly, the two groups had no cardiovascular differences. Preanesthetic behavior patterns were the same (P > .05), with 85% of the tramadol group being drowsy but awake versus 90% in the placebo group. Similarly satisfactory induction behavior was seen in 95% of the tramadol group and 90% of the placebo group. Recovery times were 48.6 minutes (SD 32.3) (T) and 43.1 minutes (SD 32.5) (P) (P > .05). It is concluded that tramadol at 3 mg/kg has no clinical respiratory depressant effect and that behavior and recovery times are unaffected. Analgesic efficacy is demonstrated.

Ambulatory Surgical Procedures↗
PubMed2001

Prescription of analgesics in general medical practice.

The aim of this study was to examine the frequency of prescription of analgesic drugs by General Practitioners in Austria, the reasons for which they are prescribed, as well as relevant organizational details. A questionnaire was designed to prospectively collect data from 14 participating General Practitioners over a period of at least 20 days each. The type of analgesic drugs prescribed during direct (doctor) or indirect (receptionist) consultations was recorded, coded according to the ATC classification and separated into first and repeat consultations. Furthermore, the diagnostic terms and the individual intensity of pain perception by the patients were noted. During 7248 consultations recorded, 1083 prescriptions of analgesics were issued. The majority of first prescriptions are issued during direct consultations, whereas a large number of repeat prescriptions are prepared for the doctor's supervision by the receptionists via indirect consultations. Almost half of the patients receive repeat prescriptions. In both, direct and indirect consultations with patients, approximately every 7th contact results in the prescription of an analgesic drug. The antirheumatic drug group is the most frequently prescribed group of painkillers whereas opioids are rarely prescribed. Selection of drugs is not clearly related to the degree of pain experienced by individual patients. Problems of the musculo-skeletal system rank first among the classifications leading to prescription of an analgesic. Pain needs quick and efficient therapy. Prescriptions of analgesics in General Practice ought to be issued in such a way as to serve this large group of patients without, however, taking extensive risks: repeat and first prescriptions issued during indirect consultations have to be precisely recorded and need the doctor's personal supervision.

Analgesics↗
PubMed2002

Augmentation of analgesic effect of ibuprofen by alprazolam in experimental model of pain.

The reports of analgesic effects of benzodiazepines are inconsistent. There is evidence of a hyperalgesic effect induced by activation of supraspinal GABAA receptors and an antinociceptive effect induced by activation of receptors located in the spinal cord (dorsal horns). The aim of the study was to discover whether the systemic administration of a benzodiazepine agent alprazolam increases the systemic analgesic efficacy of non-opioid analgesic ibuprofen. Experimental studies combining these agents have not yet been published. We used three experimental methods - writhing test (with acetic acid), tail-flick test and plantar test to assess analgesic action. The drugs were administered orally. Augmentation of the analgesic effect of ibuprofen by alprazolam was proved for the writhing test at a dose of 30 mg/kg of ibuprofen and alprazolam 1 mg/kg. The reaction time of the combination was significantly prolonged in comparison with ibuprofen alone. The results of the tail-flick test and plantar test were negative. The effect of ibuprofen was not enhanced by alprazolam in tests of acute thermal pain. Our results have demonstrated that the analgesic action of ibuprofen is only weakly enhanced by alprazolam.

Acetic Acid↗
PubMed1979

[Salicylamide-- a potential pain-remedy alternative in the analgesic asthma syndrome].

Central pathogenetic mechanism of the analgesics-asthma-syndrome is very probably an analgesics-conditioned inhibition of the prostaglandin-biosynthesis (cyclooxygenase). Salicylamide, an analgesic without effect on the prostaglandin synthesis was in the oral exposition test of 18 patients with proved analgesics-asthma-syndrome in the dosage of 500 mg subjectively and objectively tolerated without reaction. Body-plethysmographically in consistent thoracic gas volume a slight decrease of the airways resistance could be registered. At the model of the isolated trachea of guinea-pigs salicylamide, in contrast to indomethacin and phenazone (prostaglandin-synthesis inhibitory substances) did not lead to an increase of the acetylcholine-induced spasm. Salcylamide can, after a tolerability test, be recommended as alternative analgesic in the analgesics-asthma-syndrome in a dosage of 500 mg.

Analgesics↗