salicylates and Pain

To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA).. PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies.. 43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=-0.30, 95% CI -0.40 to -0.20) and improving function (SMD=-0.35, 95% CI -0.45 to -0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=-0.81, 95% CI -1.12 to -0.52) and piroxicam was most effective for functional improvement (SMD=-1.04, 95% CI -1.60 to -0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs.. Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study.

Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Bayes Theorem; Humans; Network Meta-Analysis; Osteoarthritis; Pain; Randomized Controlled Trials as Topic; Salicylates; Transdermal Patch

Rubefacients (containing salicylates or nicotinamides) cause irritation of the skin, and are believed to relieve various musculoskeletal pains. They are available on prescription, and are common components in over-the-counter remedies. A non-Cochrane review in 2004 found limited evidence for efficacy.. To review current evidence for efficacy and safety of topically applied rubefacients in acute and chronic painful musculoskeletal conditions in adults.. Cochrane CENTRAL, MEDLINE, EMBASE, the Oxford Pain Relief Database, and reference lists of articles were searched; last search December 2008.. Randomised, double blind, placebo or active controlled clinical trials of topical rubefacient for musculoskeletal pain in adults, with at least 10 participants per treatment arm, and reporting outcomes at close to 7 (minimum 3, maximum 10) days for acute conditions and 14 (minimum 7) days or longer for chronic conditions.. Two review authors independently assessed trials for inclusion and quality, and extracted data. Relative benefit or risk and number needed to treat to benefit or harm (NNT or NNH) were calculated with 95% confidence intervals (CI). Acute and chronic conditions were analysed separately.. Six placebo and one active controlled studies (560 and 137 participants) in acute pain, and seven placebo and two active controlled studies (489 and 90 participants) in chronic pain were included. All used topical salicylates. The evidence in acute conditions was not robust; using only better quality, valid studies, there was no difference between topical rubefacient and topical control, though overall, including lower quality studies, the NNT for clinical success compared with placebo was 3.2 (95% CI: 2.4 to 4.9). In chronic conditions the NNT was 6.2 (95% CI: 4.0 to 13) compared with topical placebo. Adverse events and withdrawals occurred more often with rubefacients than placebo, but analyses were sensitive to inclusion of individual studies, so not robust. There were insufficient data to draw conclusions against active controls.. The evidence does not support the use of topical rubefacients containing salicylates for acute injuries, and suggests that in chronic conditions their efficacy compares poorly with topical non-steroidal antiinflammatory drugs (NSAIDs). Topical salicylates seem to be relatively well tolerated in the short-term, based on limited data. There is no evidence at all for topical rubefacients with other components.

Topics: Acute Disease; Administration, Topical; Adult; Chronic Disease; Humans; Irritants; Musculoskeletal Diseases; Pain; Salicylates

NSAIDs are useful analgesics for many pain states, especially those involving inflammation. Their use is frequently overlooked in patients with postoperative and chronic pain. Unless there is a contraindication, the use of an NSAID should be routinely considered to manage acute pain, chronic cancer, and noncancer pain.

Topics: Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Humans; Pain; Salicylates

Nonopioid analgesics represent a varied collection of analgesic agents, many of which also possess antipyretic or anti-inflammatory actions. As a group, nonopioid analgesics represent reasonable first-line analgesics for a variety of mild to moderate painful conditions and also often may be useful in conjunction with other analgesics (eg, opioids) for a myriad of severe painful conditions. Clinicians treating pain should be familiar with the actions, adverse effects, and individual agents in the group of nonopioid analgesics.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Humans; Mice; Pain; Salicylates

Osteoid osteoma and radiofrequency Osteoid osteoma relates to a benign skeletal neoplasm, smaller than 2 cm in diameter, composed of osteoid, highly vascularized connective tissue and surrounded by a ring of bone sclerosis. Its aetiology remains unknown. It affects twice more males than female patients and occurs usually between 5 and 40 years old. Long bones and spine are the most involved areas but the whole skeleton can be involved. Clinical manifestations can include local pain (increased at night and decreased by activity) and relief with salicylates administration. CT guided radiofrequency ablation of osteoid osteoma is in comparison to surgery less invasive, time saving and economic technique with excellent long term results.

Topics: Bone Neoplasms; Catheter Ablation; Female; Health Care Costs; Humans; Male; Osteoma, Osteoid; Pain; Salicylates; Sex Factors; Tomography, X-Ray Computed

To determine the efficacy and safety of topical rubefacients containing salicylates in acute and chronic pain.. Electronic databases and manufacturers of salicylates.. Randomised double blind trials comparing topical rubefacients with placebo or another active treatment, in adults with acute or chronic pain, and reporting dichotomous information, around a 50% reduction in pain, and analyses at one week for acute conditions and two weeks for chronic conditions.. Relative benefit and number needed to treat, analysis of adverse events, and withdrawals.. Three double blind placebo controlled trials had information on 182 patients with acute conditions. Topical salicylate was significantly better than placebo (relative benefit 3.6, 95% confidence interval 2.4 to 5.6; number needed to treat 2.1, 1.7 to 2.8). Six double blind placebo controlled trials had information on 429 patients with chronic conditions. Topical salicylate was significantly better than placebo (relative benefit 1.5, 1.3 to 1.9; number needed to treat 5.3, 3.6 to 10.2), but larger, more valid studies were without significant effect. Local adverse events and withdrawals were generally rare in trials that reported them.. Based on limited information, topically applied rubefacients containing salicylates may be efficacious in the treatment of acute pain. Trials of musculoskeletal and arthritic pain suggested moderate to poor efficacy. Adverse events were rare in studies of acute pain and poorly reported in those of chronic pain. Efficacy estimates for rubefacients are unreliable owing to a lack of good clinical trials.

Topics: Acute Disease; Administration, Topical; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Double-Blind Method; Humans; Irritants; Pain; Randomized Controlled Trials as Topic; Salicylates; Treatment Outcome

Nonopioid and adjuvant analgesics encompass a huge range of heterogenous drugs that differ chemically and mechanistically. These drugs generally are prescribed for mild-to-moderate pain, as coanalgesics for severe pain, or to target specific pain-generating mechanisms. This article provides an overview of some of the more commonly used nonopioid and adjuvant analgesics used to treat chronic pain, including salicylates, acetaminophen, nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, anticonvulsants, N-Methyl-D-Aspartate receptor antagonists, lidocaine, skeletal muscle relaxants, and topical analgesics.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Antidepressive Agents, Tricyclic; Chemotherapy, Adjuvant; Chronic Disease; Drug Monitoring; Humans; Lidocaine; Neuromuscular Agents; Nursing Assessment; Pain; Pain Measurement; Patient Selection; Receptors, N-Methyl-D-Aspartate; Salicylates; Treatment Outcome

Dermal chemical peeling is a very satisfying procedure for patients and physicians alike. Although not providing the ablation of deep wrinkles and scars that dermabrasion and laser procedures may accomplish, trichloroacetic acid peels usually result in few complications and rapid recovery. Patients can usually expect photographic improvement in their skin. The results are usually long lasting, and most patients do not need to repeat dermal peels for at least 2 years. Of all resurfacing procedures, dermal peeling provides the best benefit-to-risk ratio.

Topics: Chemexfoliation; Drug Combinations; Ethanol; Humans; Lactic Acid; Pain; Postoperative Care; Resorcinols; Salicylates; Trichloroacetic Acid

In the management of chronic pain conditions, the combination of pharmacologic measures with physical and psychologic modalities becomes even more important. A pain clinic and pain consultation service are one model that facilitates this combined approach. Initial management of mild to moderate pain begins with nonopioid analgesics such as acetaminophen and NSAIDs. Persistent severe pain of a neuropathic character merits careful trials of antidepressants or anticonvulsants. Traditionally, use of opioids for chronic pain not due to cancer has been discouraged for adults as well as children. Recently, this view was challenged by reports by Portenoy and Foley and by Taub, who followed a group of adults with chronic pain due to a variety of conditions. They found that the majority of these patients, if managed with opioids on a regular schedule as part of an overall treatment program, could be made comfortable and were able to increase their level of functioning for several years. In general, dosage escalation and compulsive drug-seeking behaviors were not seen. Since this report was retrospective and did not involve children, caution must be applied in extrapolating these findings to children. For example, remarkably little is known about the effects of chronic opioid administration in childhood on growth and development. Certainly, this issue deserves further study before general recommendations can be made. It seems prudent to emphasize the importance of maximizing nonpharmacologic and nonopioid approaches in the management of chronic pain in children prior to embarking on long-term use of opioids.

Topics: Acetaminophen; Adolescent; Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents, Tricyclic; Child; Dose-Response Relationship, Drug; Humans; Pain; Salicylates; Substance-Related Disorders

Nonsteroidal anti-inflammatory drugs (NSAIDs) provide potent analgesic, anti-inflammatory activity as a result of their inhibition of prostaglandin synthesis. They are highly bound to plasma proteins and have half-lives that vary from two hours to more than 24 hours. While gastrointestinal reactions are well known, the renal and hepatic toxicities of NSAIDs have only recently been characterized. Elderly patients in general may be at risk of toxicity and should be evaluated frequently.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Dysmenorrhea; Female; Humans; Joint Diseases; Kinetics; Pain; Salicylates

The largest group of non-narcotic analgesics are the arylalkanoic acid derivatives, comprising derivatives of arylacetic acid, propionic acid, heteraryl acetic acid and indole acetic acid. Common to all of these drugs is their inhibition of prostaglandin biosynthesis, which contributes to their analgesic and other pharmacological properties as well as to their principal side effect, gastrointestinal irritation. Although these drugs all cause some gastric microbleeding, they do so to a lesser extent than aspirin. The arylalkanoic acid derivatives, as well as the anthranilic acid and oxicam derivatives, are peripherally acting as evidenced by their lack of activity in classical tests of central analgesic activity. After oral administration of these drugs, their peak plasma concentrations are generally attained in 1 to 3 hours; absorption is not generally influenced by food. Volume of distribution is mostly low (less than 0.2 L/kg) and protein binding is high (usually 95 to 99%). Elimination is by glucuronide formation for several of the propionic acid derivatives and generally by biotransformation for derivatives of arylacetic acid, indole and indene acetic acid, and the oxicams. The elimination half-life of the arylalkanoic acid derivatives is in most instances about 2 to 5 hours, although notable exceptions include carprofen (approximately equal to 20 h), fenbufen (10 h), naproxen (12-15 h) and sulindac (16 h for the active metabolite). The elimination half-life of indomethacin varies considerably between and within individuals. Piroxicam has the longest half-life, averaging 45 hours. The pharmacokinetic properties of the anthranilic acid derivatives (fenamates, glafenine) generally resemble those of the arylacetic acids. Few clinically significant drug interactions are associated with concomitant administration of the arylalkanoic acids or piroxicam and other drugs. Since the arylalkanoic acids are highly bound to plasma proteins (mainly albumin) there is a theoretical potential for displacement reactions with drugs that are used at plasma concentrations high enough to exceed the binding capacity of their own primary binding sites. However, such reactions have rarely been reported. Although the concomitant administration of aspirin and several of the propionic acid derivatives results in a significant decrease in the plasma concentration of the latter, the clinical significance of such interactions is uncertain and probably minimal.(ABSTRACT TRUNCATED AT

Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Interactions; Humans; Pain; Salicylates

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It has been studied in osteoarthritis, pain resulting from musculoskeketal sprains and strains and from minor surgery and cancer. The duration of its analgesic effect is longer than that of aspirin and diflunisal is effective when given twice daily. Diflunisal is not metabolised to salicylic acid and has a lesser effect than aspirin on platelet function in vivo. In osteoarthritis, diflunisal appears comparable in efficacy to moderate doses of aspirin (2 to 3g daily), but is better tolerated. It has not been compared with the most active phenylalkanoic acid derivatives such as naproxen in adequate numbers of patients. Diflunisal is comparable with glafenine in pain and with propoxyphene/paracetamol combinations and oxyphenbutazone in pain and in musculoskeletal strains and sprains. As with other non-steroidal agents, gastrointestinal complaints are the most frequently reported side effects.

Topics: Diflunisal; Drug Interactions; Humans; Kinetics; Osteoarthritis; Pain; Salicylates; Sprains and Strains

Topics: Activities of Daily Living; Arthritis, Rheumatoid; Bursitis; Chloroquine; Diagnosis, Differential; Finger Joint; Gold; Gout; Hot Temperature; Humans; Hydroxychloroquine; Methylprednisolone; Neuralgia; Osteoarthritis; Pain; Physical Examination; Physical Exertion; Physical Therapy Modalities; Prednisolone; Rest; Salicylates; Synovectomy; Triamcinolone; Wrist Joint

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Aspirin; Blood Chemical Analysis; Bradykinin; Bronchi; Cats; Chemical Phenomena; Chemistry; Constriction; Dogs; Enzyme Inhibitors; Epithelium; Exudates and Transudates; Gastric Mucosa; Guinea Pigs; Haplorhini; Hemostasis; Histamine; Inflammation; Kidney Tubules; Mice; Muscle, Smooth; Muscles; Neurons; Pain; Peptides; Rabbits; Rats; Salicylates

Antibiotics and retinoids have been used for acne vulgaris for decades. Though effective, each has its own drawbacks. Chemical peels have been used for treatment of acne vulgaris with inadequate clinical evidence. We sought to determine the efficacy and safety of Jessner's solution (JS) in comparison with salicylic acid (SA) 30% in the management of acne vulgaris and postacne hyperpigmentation in patients with colored skin.. A total of 36 subjects (94.5% Fitzpatick Type IV-V) were recruited in this randomized double-blinded, split-face, controlled trial. Each side of the face was randomly assigned for treatment with either JS or SA. Subjects were treated once fortnightly for a total of three sessions. Lesion counting, Michaelsson acne score (MAS), photographs, and postacne hyperpigmentation index (PAHPI) were used to objectively assess the improvement. Complications were assessed during each visit. Statistical analysis was conducted using SPSS v22.0. Significance was set at P = 0.05.. At the end of therapy, significant reduction in inflammatory, noninflammatory lesions, MAS, and PAHPI scores (P < 0.001, respectively) were noted in comparison to baseline. Mixed model analysis revealed no significant outcome difference between the two groups. Patients who reported good and very good outcome were 76.4% (JS) and 85.3% (SA). Burning, stinging sensation, and exfoliation were the common complications reported. Postinflammatory hyperpigmentation was reported only once in the JS arm.. Both JS and SA were equally effective in the treatment of acne vulgaris and reducing postacne hyperpigmentation in patients with colored skin.

Topics: Acne Vulgaris; Adult; Chemexfoliation; Double-Blind Method; Drug Combinations; Ethanol; Facial Dermatoses; Female; Humans; Hyperpigmentation; Keratolytic Agents; Lactic Acid; Male; Pain; Resorcinols; Salicylates; Salicylic Acid; Severity of Illness Index; Skin Pigmentation; Treatment Outcome; Young Adult

Hot-iron branding is painful for cattle, but little is known about how long this pain lasts or effective alleviation methods. Previous work with pigs indicated that cooling burns with a gel (active ingredient: tea tree oil) improved healing compared to untreated wounds. Steers (210±21 kg) were hot-iron branded and allocated to 1 of 3 treatments: control (n=24), 1 gel application immediately after branding (1X; n=12), or 2 gel applications, 1 immediately after branding and one 1 d later (2X; n=12). Pain sensitivity was assessed by applying a known and increasing force with a von Frey anesthesiometer in 5 locations (in the center, at the top of, and 5 and 10 cm above the brand and on the equivalent location on the nonbranded side of the body) until animals showed a behavioral response. Healing was measured with a 6-point scale (1=fresh brand and 6=no scabbing and fully repigmented). Both measures, along with weight gain and surface temperature of the wound, were recorded before and 1, 2, 3, 7, 14, 21, 28, 35, 56, and 70 d after branding. The gel cooled the brand, with the most obvious differences on the day it was applied (3.7 to 4.2°C cooler than control; day×gel interaction, P=0.004). All wounds were at least partially repigmented by 70 d, but only 46% of brands were fully healed at this time. The healing process was slowed when a gel was applied twice (e.g., at 21 d, healing score of 2.5±0.1 and 2.7±0.1 vs. 2.0±0.2 for control and 1X vs. 2X, respectively; P=0.001). Brands tended to remain painful throughout the 70 d (in the center of the brand; before vs. d 1-35, P≤0.001; d 56, P=0.058; and d 70, P=0.092). Overall, gel had little effect on pain sensitivity. Weight gain was reduced on d 1 after branding compared to all other time points (P<0.001) but was not affected by gel application (P=0.277). In conclusion, applying gel did not improve outcomes after branding. In addition, by 70 d after the procedure, hot-iron brands still tended to be more painful than nonbranded tissue and 54% were not fully healed. These results raise additional animal welfare concerns about hot-iron branding.

Topics: Analgesics; Animal Husbandry; Animal Welfare; Animals; Body Temperature; Burns; Cattle; Gels; Hot Temperature; Male; Pain; Salicylates; Thermography; Time Factors; Treatment Outcome; Wound Healing

Alcohol exposure alters oral mucosa. Patient compliance with mouthwash use may be reduced by oral pain resulting from rinsing with alcohol-containing mouthwash. However, information regarding the effects of alcohol consumption and mouthwash alcohol concentration on oral pain is limited. In this double-blind, randomized, controlled cross-over study, we investigated the effects of alcohol consumption status and mouthwash alcohol concentration on response to and perception of oral pain induced by alcohol-containing mouthwash. Fifty healthy men aged 33 to 56 years were enrolled and classified as drinkers and nondrinkers according to self-reported alcohol consumption. All subjects rinsed with two commercially available mouthwash products (which contained high and low concentrations of alcohol) and a negative control, in randomized order. Time of onset of oral pain, time of cessation of oral pain (after mouthwash expectoration), and pain duration were recorded, and oral pain intensity was recorded on a verbal rating scale. Drinkers had later oral pain onset and lower pain intensity. High-alcohol mouthwash was associated with earlier pain onset and greater pain intensity. In addition, oral pain cessation was later and pain duration was longer in nondrinkers rinsing with high-alcohol mouthwash. In conclusion, alcohol consumption status and mouthwash alcohol concentration were associated with onset and intensity of oral pain.

Topics: Adult; Alcohol Drinking; Benzoates; Cross-Over Studies; Double-Blind Method; Drug Combinations; Ethanol; Humans; Male; Middle Aged; Mouth Mucosa; Mouthwashes; Pain; Pain Measurement; Pain Perception; Salicylates; Sodium Dodecyl Sulfate; Solvents; Terpenes; Time Factors

To test the hypothesis that using Listerine mouthwash prior to administration of topical nasal lidocaine will result in improved pain and comfort outcomes during flexible nasolaryngoscopy (FNL).. Randomized, controlled trial.. A total of 120 patients were randomized to receive a combination of either treatment or placebo mouthwash followed by treatment or placebo nasal spray prior to an FNL examination.. Pain and discomfort using a 100 mm visual analogue scale.. The use of lidocaine significantly reduced pain (p = .011) and discomfort (p = .008) compared to placebo nasal spray. Using Listerine prior to administration of lidocaine resulted in the largest reductions. Patients having an extended nasal examination reported more pain (p = .001) and discomfort (p = .03) levels while demonstrating a greater benefit of topical lidocaine compared to those undergoing a primary laryngeal examination (p < .001).. Using Listerine prior to application of lidocaine nasal spray reduces the pain and discomfort of FNL. This effect was most clinically significant in patients undergoing an extended or full bilateral nasal examination.

Topics: Administration, Topical; Anesthetics, Local; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Laryngoscopy; Lidocaine; Male; Middle Aged; Mouthwashes; Pain; Pain Measurement; Patient Satisfaction; Prospective Studies; Salicylates; Terpenes; Treatment Outcome

The side effects of chlorhexidine (CHX) have stimulated the search for alternative antiplaque agents such as amine fluoride/stannous fluoride (ASF) and essential oils (EO). The aim of the study was to investigate the plaque-inhibiting effects of two commercially available mouthrinses containing ASF and EO, respectively.. The study was an observer-masked, randomized, 5 x 5 Latin square cross-over design, balanced for carryover effects, involving 15 volunteers in a 4-day plaque regrowth model. A 0.12% CHX rinse and a saline solution served as positive and negative controls, respectively. On day 1, subjects received professional prophylaxis, suspended oral hygiene measures, and commenced rinsing with their allocated rinses. On day 5, subjects were scored for disclosed plaque. The ASF rinse was tested at two dosages: 10 and 20 ml (ASF-10 and ASF-20, respectively).. The ASF and EO rinses showed a significant inhibition of plaque regrowth compared to saline (P <0.0001), but the lowest plaque indices were obtained with the CHX product (P <0.01). There were no significant differences among products containing ASF-10, ASF-20, and EO (P >0.05). There was no correlation between the occurrence of side effects and the use of a particular rinse product (P >0.2).. ASF and EO mouthrinses exerted effective and similar plaque inhibition. The two dosages tested for ASF did not differ in plaque reduction. These findings, together with those from long-term trials, suggest that ASF and EO rinses may represent effective alternatives to CHX rinse as adjuncts to oral hygiene.

Topics: Adult; Amines; Anti-Infective Agents, Local; Chlorhexidine; Cross-Over Studies; Dental Plaque; Dental Plaque Index; Drug Combinations; Female; Humans; Male; Mouth Diseases; Mouthwashes; Oils, Volatile; Pain; Salicylates; Single-Blind Method; Taste Disorders; Terpenes; Tin Fluorides

The aim of this confirmative, monocentre, double-blind, controlled clinical trial was to investigate whether different escin combinations show differences in comparison to placebo with regard to pain reactions in the topical treatment of sports injuries. A total of 126 patients with blunt injuries of the extremities were randomly allocated to four parallel groups: Reparil-Gel N (n = 32), Reparil-Gel (n = 31), Reparil-Sportgel (n = 32) and a placebo gel (n = 31). All patients were evaluated for efficacy (intention to treat) and tolerability. A per-protocol analysis was also carried out, in which 12 of the 126 patients were excluded due to protocol violations. The intention-to-treat and per-protocol analyses produced similar results. The patients had suffered contusions while participating in soccer, hockey, karate, tae-kwon-do, handball, American football, rugby or tennis. The measured variable was the pressure required at the centre of the lesion to elicit the first pain reaction (tenderness reaction) at measuring time 0 (baseline) and then 1, 2, 3, 4, 6 and 24 h after the injury. The primary variable was the area under the curve (AUC) for tenderness over a six-hour period. The mean AUC differed significantly in the four groups (Kruskal-Wallis test p = 0.0001). Then six pairwise comparisons of two treatment groups each were carried out using the Mann-Whitney test. To control the multiple significance level of 5%, the adjusted p-values according to the Holm-Shaffer method were used in these tests. The three active gels were significantly superior to the placebo gel (Mann-Whitney test, p = 0.0004 in each case) in terms of the AUC. There were no significant differences between the active test substances in terms of the primary variable. The intensity of the pain was also measured on a visual analogue scale (VAS). The pain diminished more rapidly with the Reparil gels than with the placebo. The tolerability of all test substances was good. No adverse events were observed in any of the 126 patients. Escin combination gels are more effective than a placebo and are also well tolerated. Therefore, they can be recommended for the treatment of blunt injuries caused during sports and leisure activities.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Arm Injuries; Athletic Injuries; Double-Blind Method; Drug Combinations; Escin; Female; Gels; Humans; Leg Injuries; Male; Pain; Pain Measurement; Patient Satisfaction; Salicylates; Wounds, Nonpenetrating

The aim of this investigation was to elucidate whether the analgesic effect was due to the local aspirin or to the systemic drug. This was done by comparing skin and plasma levels of acetylsalicylic acid (ASA) and salicylic acid (SA) after topically administered ASA/diethyl ether (ADE) mixture in acute herpetic neuralgia (AHN) and postherpetic neuralgia (PHN). The analgesia and the plasma and skin levels of ASA were also determined after oral administration of aspirin.. Nineteen patients, 11 (57.9%) with AHN and 8 (42.1 %) with PHN were given, on different days, a single 500-mg oral dose of ASA or a topical dose (750 mg) of (ADE) daubed onto the painful skin. The analgesic effect was assessed by means of a visual analogue scale (VAS). Overall pain relief was graded as: excellent, good, fair, or poor. AHN as well as PHN patients had severe pain at baseline (6.83 and 5.93). Levels of ASA and SA in plasma and in the stratum corneum after adhesive tape stripping of the treated area were determined by HPLC.. After ADE application, the analgesic effect was very rapid and VAS scores were lower than at baseline. Pain significantly decreased by 82.6% after topical and 15.4% after oral ASA. After ADE, 95% of the patients had excellent or good pain relief, but after oral administration 79% of the patients had a poor response. Pain relief was similar in the two subgroups after ADE. Skin concentrations of ASA, but not of SA, after ADE were about 80- to 100-fold those after oral administration. Levels of ASA and SA in plasma after oral administration were similar to those previously found, but after ADE were undetectable or very low. Patients with excellent pain relief showed a trend towards higher ASA skin concentrations.. The analgesic effect can be obtained only after topical administration, because by this route the skin levels of ASA are much higher than after oral administration. The mechanism is exclusively local; there are no active drugs in plasma after topical administration.

Topics: Acute Disease; Administration, Oral; Administration, Topical; Aged; Analgesics; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cross-Over Studies; Double-Blind Method; Ether; Female; Herpes Zoster; Herpesviridae Infections; Humans; Male; Middle Aged; Neuralgia; Pain; Pain Measurement; Salicylates; Salicylic Acid; Skin; Solvents; Treatment Outcome

In a human acid pain model, which uses continuous intradermal pressure infusion of a phosphate-buffered solution (pH 5.2) to induce localized non-adapting pain, the flow was adjusted to result in constant pain ratings of about 20% or 50% on a visual analog scale (VAS). Six volunteers in each group participated in 4 different placebo-controlled double-blind cross-over studies to measure rapidly evolving cutaneous analgesia from topically applied new ointment formulations of acetylsalicylic acid (ASA) and salicylic acid (SA) as well as of commercial ibuprofen and benzocain creams. Similar, log-linear dose-response curves were found for both ASA and SA, significant in effect at 3 g/kg and higher drug contents and reaching saturation level at 15 or 30 g/kg, respectively, which, 20 min after application, caused a mean pain suppression of 95% using ASA and 80% using SA. Half-maximal effects were achieved using 3 g/kg ASA or 15 g/kg SA. The SA action was also clearly slower to develop. With an increased flow of the acidic buffer, producing lower effective tissue pH and more intense pain, the effect of ASA and SA decreased to 73% pain suppression. A competitive mechanism of both drug effects was suggested by the fact that, with 15 g/kg ASA and SA, pain reduction could be reversed by increasing the buffer flow by a factor of 1.75, on average. Commercial ibuprofen (50 g/kg) and benzocain creams (100 g/kg) were comparably as effective as ASA and SA, but the local anesthetic caused a loss of all cutaneous sensations while the touch threshold (von Frey) under the specific analgesics was the same as under the placebo ointment. Thus, topical applications of non-steroidal anti-inflammatory drugs (NSAIDS) dissolved in different ointment formulations have proven dose-dependently effective and specific in suppressing experimental acidotic pain by a local and competitive mechanism.

Topics: Administration, Topical; Adolescent; Adult; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Dose-Response Relationship, Drug; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pain; Palliative Care; Salicylates; Salicylic Acid; Skin

To investigate the efficacy of salsalate, a nonacetylated salicylate, in the treatment of patients with rheumatoid arthritis (RA).. Three hundred and one patients meeting the ACR criteria for RA were drawn from 16 centers. After withdrawal of nonsteroidal antiinflammatory drugs (NSAID) and subsequent flare, patients were randomized to receive either salsalate or diclofenac for 8 weeks, according to a double blind, double dummy protocol. Initial doses of salsalate 3.0 g/day and diclofenac 75 mg/day were titrated for the first 5 weeks. The primary outcome measure was a multivariate analysis at 8 weeks of tender joint count, pain, visual analog scale score, and physician's global assessment.. One hundred and ninety patients completed the study. The mean stabilized dose of salsalate was 3.55 g/day, and that of diclofenac 112 mg/day. Discontinuations were due to lack of efficacy (17 salsalate vs 15 diclofenac); adverse events [19 salsalate (mainly tinnitus and hearing loss; p = 0.0001 and p = 0.04, respectively) vs 9 diclofenac]; laboratory abnormalities (3 salsalate vs 1 diclofenac); and other reasons, including protocol violations, intercurrent illness, and personal factors (24 salsalate vs 23 diclofenac). Both treatments produced significant improvement from flare (p < 0.0001). Post hoc power analysis showed that the study had sufficient power (0.60 to 0.90) to detect clinically important differences between the 2 drugs in the primary outcome measures; however, no statistically significant (p = 0.29) or clinically important treatment differences were recorded. Other than a difference in erythrocyte sedimentation rate that favored salsalate, there were no significant differences in secondary outcome measures between the 2 groups. All outcomes showed a tendency for more improvement with salsalate.. Salsalate is as efficacious as diclofenac. Salsalate may be considered an alternative to other NSAID in the first line treatment of patients with RA.

Topics: Aged; Arthritis, Rheumatoid; Diclofenac; Double-Blind Method; Female; Humans; Male; Middle Aged; Multivariate Analysis; Pain; Salicylates; Treatment Outcome

Twenty-six patients with painful, bony metastases were recruited into a randomized, double-blind, single dose, two-treatment, three-part crossover study of choline magnesium trisalicylate (CMT) and placebo. Assessments were made prior to and at one, two, three and four hours after dosing. Bone pain caused by metastatic cancer was significantly relieved one hour after the administration of 1500 mg CMT (p = 0.04). At all four time points the pain was less than baseline with CMT and at three time points greater than baseline with placebo but these results did not reach statistical significance. The summed pain intensity difference for patients was greater with CMT than with placebo, but this also did not reach significance. The incidence of volunteered side-effects was similar for both treatments. The results suggest that a nonacetylating, nonsteroidal anti-inflammatory drug may have a role complementary to that of an opioid in the management of metastatic bone pain.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Bone Neoplasms; Choline; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Pain; Pain Measurement; Palliative Care; Salicylates

A double-blind, randomized analgesic trial was carried out in 150 patients undergoing surgical removal of their 2 impacted lower wisdom teeth. The analgesic efficacy of effervescent acetaminophen 500 or 1000 mg in a 2-dose regimen was compared with that of diflunisal 500 mg in a single dose. Each dose was taken when subjectively needed and the pain intensity was measured on a visual analog scale during the 10-hour period after first medication. The best pain reduction was achieved with diflunisal. The difference between diflunisal 500 mg and acetaminophen 1000 mg was significant, as was that between acetaminophen 1000 and 500 mg. The peak effect after the first dose occurred later but was greater with diflunisal than with acetaminophen. Patients needing analgesics at low pain intensities seemed to discriminate better between treatments, and the efficacy of acetaminophen was weakly dependent on the initial pain intensity. This intensity was difficult to predict, and only a poor correlation was found between the initial pain intensity and the patient's prior estimate of this.

Topics: Acetaminophen; Adult; Clinical Trials as Topic; Diflunisal; Female; Humans; Male; Pain; Salicylates; Tooth, Impacted

Using controlled long lasting noxious squeeze stimuli applied to the interdigital webs we have tried to develop experimental methods allowing us to measure the effects of peripherally acting analgesics. In the present double-blind cross-over study with 12 subjects we tested the effects of aspirin (1000 and 1500 mg) vs. placebo on subjective pain induced by alternately applied 12 N (Newton) and 8 N stimuli. During the sessions blood samples were taken in regular intervals to measure acetylsalicylate (ASA)- and salicylate (SA)-plasma levels. Analyses of variance were computed with several psychophysical parameters. Both the '12 N' and the '8 N' ratings discriminated between placebo and aspirin, however, only the ratings obtained from the stronger stimuli discriminated between two doses of aspirin. Subsequently we computed analyses of covariance with the ASA- and SA-plasma levels as covariates. Significant (negative) correlations of pain ratings and SA-plasma levels were found for the high dose of aspirin, but there were no significant correlations of ASA levels and ratings.

Topics: Analgesia; Analysis of Variance; Aspirin; Clinical Trials as Topic; Double-Blind Method; Humans; Male; Pain; Pain Measurement; Salicylates; Salicylic Acid

The efficacy and tolerability of diflunisal (500 mg orally, twice daily) and piroxicam (20 mg orally, once daily) were compared in a 12-week open-label study in 44 patients with active rheumatoid arthritis. Both medications were equally effective and generally well tolerated. No significant differences were found between drug groups. Both groups showed statistically significant improvement in the overall number of swollen and tender joints, painful joint count, and the patients' assessment of pain and disease severity. Two (9%) of 23 patients in the diflunisal group and one (5%) of 21 patients in the piroxicam group reported adverse effects. Only one patient withdrew from the study because of side effects (lightheadedness during use of diflunisal). It is concluded that both diflunisal and piroxicam are highly effective and generally well tolerated in the management of rheumatoid arthritis.

Topics: Adult; Aged; Arthritis, Rheumatoid; Clinical Trials as Topic; Diflunisal; Female; Humans; Male; Middle Aged; Pain; Piroxicam; Prospective Studies; Random Allocation; Salicylates

Acute soft tissue injuries create pain and limitation of function. Treatment requires analgesia and time for full recovery. Acetaminophen with codeine (650 mg plus 60 mg, respectively, every 4 to 6 hours) is used frequently as the analgesic of choice. Diflunisal (1,000 mg initially then 500 mg twice a day) vs acetaminophen with codeine was prospectively studied in the treatment of acute mild to moderate pain from soft tissue injuries. Thirty-five patients with acute strains, sprains, or low back pain were randomized to treatment (17 acetaminophen with codeine vs 18 diflunisal). Both groups were similar in the amount of pain and type of injury at initiation of therapy. Patient pain rating went from 3.3 +/- 0.6 to 1.6 +/- 1.5 for acetaminophen with codeine and from 3.3 +/- 0.6 to 1.3 +/- 1.1 for diflunisal. However, 65 percent of acetaminophen with codeine patients experienced side effects, with 35 percent of these patients stopping the medication because of intolerable side effects. In the diflunisal group, 28 percent of the patients experienced side effects and 5 percent had to stop the medication early. Diflunisal was found to be an effective analgesic in mild to moderate pain of acute soft tissue injuries, and caused fewer and more tolerable side effects than did acetaminophen with codeine.

Topics: Acetaminophen; Acute Disease; Adult; Back Pain; Clinical Trials as Topic; Codeine; Diflunisal; Drug Combinations; Drug Tolerance; Female; Humans; Male; Pain; Prospective Studies; Random Allocation; Salicylates; Sprains and Strains

The emergency physician treats many patients with mild to moderate pain due to musculoskeletal injury. The physician must consider the extent of injury, the patient's medication history, and the potential for abuse when prescribing an oral analgesic. A study was designed to compare the efficacy of two oral analgesics, one containing a narcotic and one nonnarcotic, in relieving mild to moderate pain associated with grade 2 ankle sprain. Forty patients were enrolled--all with moderate pain--and were randomly allocated to treatment with either diflunisal or acetaminophen with codeine. Both analgesic agents were equally effective in relieving the pain. Side effects were experienced by six patients, all of whom were receiving acetaminophen with codeine; none of the patients given diflunisal noted side effects. Global assessments of the efficacy and tolerability of the study drugs showed that 89% of 19 patients given diflunisal and 43% of 21 patients given acetaminophen with codeine considered their respective analgesics excellent or very good.

Topics: Acetaminophen; Adult; Ankle Injuries; Codeine; Diflunisal; Drug Combinations; Edema; Female; Humans; Male; Middle Aged; Pain; Prospective Studies; Random Allocation; Salicylates; Sprains and Strains

Fifty college athletes with acute sprains and strains from football-related activities were randomly assigned to treatment with either diflunisal or acetaminophen with codeine for seven days. Additional treatment in both groups included rest, elevation, local application of cold or heat, splinting, and physical therapy, as indicated. Both treatment groups exhibited clinically significant improvements in pain, tenderness, and swelling. The results of this study show that diflunisal, a peripherally acting nonnarcotic nonsteroidal anti-inflammatory agent with analgesic properties, was as effective as acetaminophen with codeine in relieving mild to moderate pain due to musculo-skeletal sprains and strains. The long duration of action of diflunisal permits less frequent dosing, an important consideration when prescribing medication for active young adults.

Topics: Acetaminophen; Adolescent; Adult; Athletic Injuries; Clinical Trials as Topic; Codeine; Diflunisal; Drug Combinations; Humans; Male; Pain; Random Allocation; Salicylates; Sprains and Strains

The efficacy and safety of the nonsteroidal anti-inflammatory drugs imidazole.2-hydroxybenzoate and sulindac were compared in 30 patients with classical or definite rheumatoid arthritis. The trial was designed as a randomized parallel-group study comprising 15 patients given imidazole.2-hydroxybenzoate and 15 given sulindac orally for 28 days. Patients in both groups improved significantly in almost all of the variables evaluated. Imidazole.2-hydroxybenzoate was more effective than sulindac on Ritchie's articular index, left hand proximal interphalangeal joint circumference, erythrocyte sedimentation rate, and C-reactive protein. The incidence of side effects was significantly higher in patients treated with sulindac.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Blood Sedimentation; C-Reactive Protein; Clinical Trials as Topic; Female; Humans; Imidazoles; Indenes; Male; Middle Aged; Pain; Random Allocation; Salicylates; Sulindac

Two nonsteroidal anti-inflammatory drugs, diflunisal and naproxen, were compared for efficacy in relieving anterior knee pain of mild to moderate severity. Of 36 patients completing the study, 20 received diflunisal and 16 received naproxen. Eleven (55%) patients given diflunisal and ten (63%) given naproxen had significant relief of pain, but there were no statistically significant differences between the two treatments. Although adverse reactions were frequent in both groups, they were not severe and they abated upon discontinuation of medication.

Topics: Adult; Clinical Trials as Topic; Diflunisal; Female; Humans; Knee Joint; Male; Naproxen; Pain; Salicylates

An open, randomized clinical study was performed to evaluate the efficacy of diflunisal versus acetaminophen with codeine in patients who underwent outpatient arthroscopy of the knee. Twenty patients were randomly assigned to each treatment group. Nineteen patients in each group successfully completed the study, which consisted of both objective and subjective evaluations. The results showed equal efficacy between the two drugs. However, a larger percentage of patients viewed diflunisal as providing good to excellent results overall compared with acetaminophen with codeine.

Topics: Acetaminophen; Adolescent; Adult; Arthroscopy; Codeine; Diflunisal; Drug Combinations; Drug Evaluation; Female; Humans; Knee Injuries; Male; Middle Aged; Pain; Random Allocation; Salicylates

A double-blind study of 43 patients undergoing excision of haemorrhoids under spinal anaesthesia was carried out to compare the analgesic effects of diflunisal (DFL, 21 patients) and dextropropoxyphene napsylate (DPN, 22 patients) on post-operative pain. Eleven patients (25%) reported no significant pain during the study indicating that they had needed no analgesic medication (4 in the DFL group and 7 in the DPN group). Thus 17 patients in the DFL group and 15 patients in the DPN group contributed to the analysis data. Seven patients in the DFL group and 9 patients in the DPN group needed additional analgesic therapy on the day of surgery. After the day of surgery the analgesic effect of both of the test medications was sufficient but DFL proved to provide slightly better pain relief than DPN. Two patients in each study group had mild adverse reactions including vomiting and epigastric pain, which were probably drug related. It is concluded that both DFL and DPN are safe and sufficiently effective treatments for pain after haemorrhoidectomy but not until one day after surgery.

Topics: Administration, Oral; Adult; Aged; Benzilates; Benzophenones; Dextropropoxyphene; Diflunisal; Dipyrone; Double-Blind Method; Drug Combinations; Female; Hemorrhoids; Humans; Male; Middle Aged; Nausea; Pain; Postoperative Period; Random Allocation; Salicylates; Vomiting

Diflunisal, a long acting antiinflammatory analgesic was compared in high (1000 mg daily) and low (750 mg daily) doses with placebo in a randomized, double blind study of 6 weeks' duration in patients with osteoarthritis of the knee. Two hundred twenty-seven patients from 47 centers completed the study--high dose 69, low dose 88 and placebo 70. Pain relief was significantly greater with both doses of diflunisal than with placebo. Both patient and investigator global opinions reflected significantly greater efficacy with diflunisal. Although there was a trend in favour of the higher dose, no statistically significant differences in efficacy were found between the 2 doses of diflunisal studied. Overall adverse reactions with diflunisal were no more frequent than with placebo, but gastrointestinal side effects were significantly greater with the higher dose.

Topics: Adult; Aged; Clinical Trials as Topic; Diflunisal; Digestive System; Female; Humans; Knee Joint; Male; Middle Aged; Osteoarthritis; Pain; Random Allocation; Salicylates

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Aspirin; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Imidazoles; Joint Diseases; Male; Middle Aged; Pain; Random Allocation; Salicylates

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Double-Blind Method; Female; Fever; Humans; Imidazoles; Male; Middle Aged; Pain; Salicylates

A report is given about a multicentric double-blind test for proof of effectiveness of two new suppository preparations with and without codeine against comparable remedies. Dolo Visano Supp. sine codeino showed a slight superiority over the reference preparation. This was proved above all for the influence upon pain and muscular overstrain. The better tolerability was marked. Dolo Visano Supp. (with codeine) showed advantages against the reference preparation. It was used in cases of severe pain, and in 88% it had a very good effect, whereas for the reference preparation this applied only in 67,9%. The assessments of physician and patients were almost alike. The myotonolytic effect has been proved equally for both of the new suppository preparations.

Topics: Arthritis; Aspirin; Clinical Trials as Topic; Codeine; Diphenhydramine; Double-Blind Method; Drug Combinations; Humans; Meprobamate; Muscle Rigidity; Nerve Compression Syndromes; Nicotinic Acids; Osteoarthritis; Pain; Plant Extracts; Salicylamides; Salicylates; Spinal Nerve Roots; Suppositories

The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal (Dolobid), a new nonsteroidal anti-inflammatory analgesic, was compared in a double-blind study with that of acetaminophen, 600 mg, the combination of acetaminophen, 600 mg, with codeine phosphate, 60 mg, and placebo in 159 oral surgery outpatients. Using a self-rating record, patients rated their pain and its relief hourly for 12 hours after medication. Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination. Diflunisal proved to have an unusually long duration of analgesic action. Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5, respectively; both doses of diflunisal were significantly superior through the end of the 12-hour observation period. None of the active treatments produced more side effects than the placebo.

Topics: Acetaminophen; Administration, Oral; Clinical Trials as Topic; Codeine; Delayed-Action Preparations; Diflunisal; Double-Blind Method; Drug Therapy, Combination; Humans; Pain; Salicylates; Surgery, Oral; Time Factors

The efficacy and safety of diflunisal versus placebo in the treatment of pain were compared in a multicenter, double-blind study of 1,037 patients treated for seven days by general practitioners. A statistically significant (P less than 0.001) difference in favor of diflunisal was seen using four evaLuation criteria. The incidence of side effects was generally low with both treatments; nevertheless, the number of patients suffering at least one side effect was greater after diflunisal than after placebo (P less than 0.05). A comparison of the profile of responders to diflunisal and to placebo showed no particular pattern.

Topics: Clinical Trials as Topic; Diflunisal; Double-Blind Method; Family Practice; Female; Humans; Male; Middle Aged; Pain; Placebos; Salicylates

Topics: Aged; Analgesics; Aspirin; Bone Diseases; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Joint Diseases; Lysine; Middle Aged; Muscular Diseases; Organophosphates; Organophosphorus Compounds; Pain; Placebos; Salicylates; Stomach

Fosfosal or 2-phosphonoxybenzoic acid is a new analgesic drug, whose analgesic activity and side effects have been determined in a double blind clinical study in comparison with placebo. The study has been done with 60 outpatients, of both sexes, which suffered musculoskeletal and arthritic pains. Patients were treated with fosfosal or placebo for eight days. The daily dose of fosfosal was 1 gram three times a day, once every 6-8 hours. The results obtained show that fosfosal has a clear analgesic activity, statistically significant versus placebo in all the parameters that were measured: pain severity, activity impairment and insomnia. The overall evaluation of the group of patients treated with fosfosal showed a marked improvement with a difference statistically significant with respect to the control group treated with placebo (p less than 0.001). The distribution of results in the fosfosal treated group was as follows: poor, 1; regular, 8; good, 10 and excellent, 6. The distribution in the placebo group was as follows: poor, 15; regular, 3; good, 2 and excellent, 0. The marked analgesic activity, the absence of side effects and the excellent gastric tolerance suggest that fosfosal is a promising new analgesic drug useful for the treatment of painful syndromes of several etiologies.

Topics: Adult; Aged; Analgesics; Arthritis; Bone Diseases; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscular Diseases; Organophosphates; Organophosphorus Compounds; Pain; Salicylates

A single-blind study was carried out in 52 patients with severe pain after Colles' fracture to assess the analgesic efficacy and tolerability of 500 mg diflunisal twice daily compared with that of 500 mg mefenamic acid given 3-times daily over a period of 5 days. The results showed that both treatments were effective in relieving pain, night pain and limitation of movement by pain, and there was no significant difference between the response in the two groups. Both drugs were tolerated and only 3 patients (2 on diflunisal) reported mild drug-related side-effects.

Topics: Adult; Aged; Colles' Fracture; Diflunisal; Female; Humans; Male; Mefenamic Acid; Middle Aged; Pain; Radius Fractures; Salicylates

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Clinical Trials as Topic; Double-Blind Method; Family Practice; Female; Humans; Male; Pain; Salicylates

A randomized double-blind study in ambulatory patients with osteoarthritis of hip and/or knee was conducted, comparing the efficacy and safety of diflunisal 500 mg daily with ibuprofen 1200 mg daily, and a period of 8 weeks. Thirty-five patients participated in the study. The results revealed no significant differences between the treatment groups with regard to the efficacy parameters.

Topics: Clinical Trials as Topic; Diflunisal; Double-Blind Method; Female; Hip Joint; Humans; Ibuprofen; Knee Joint; Male; Middle Aged; Osteoarthritis; Pain; Salicylates

The analgesic efficacy of fendosal, a new nonsteroidal anti-inflammatory agent structurally related to salicylic acid, was compared with that of aspirin and placebo in 100 patients with postpartum uterine pain in a single oral dose, parallel, stratified, randomized, double-blind design. With 650 mg aspirin and with 200 or 400 mg fendosal, but not with 100 mg, analgesic effects, as measured subjectively by mean pain intensity scores, began within 1 hr and had similar time-effect patterns for the first 4 or 5 hr. Thereafter with the 2 higher doses of fendosal analgesia contimued to increase, reaching a peak at 6 hr (p less than 0.05) and persisting beyond 7 hr (p less than 0.01), whereas there was no aspirin analgesia after the fifth hour. With 100 mg fendosal time of onset tended to be delayed 2 hr or more, and duration was short. The most effective treatment (largest mean 7-hr sum of pain intensity difference [SPID] scores) was 400 mg fendosal (p less than 0.01); 200 mg fendosal was rated second (p less than 0.01), 650 mg aspirin, third (p less than 0.05), 100 mg fendosal, fourth, and placebo, fifth. There was no significant side effects. These results demonstrate the efficacy of single doses of fendosal as well as the dose-dependent magnitude and time course of effects on postpartum uterine pain.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Indoles; Pain; Postpartum Period; Pregnancy; Salicylates; Time Factors

In a preliminary open study of salsalate (3 g daily for 4 weeks) in 61 patients with rheumatoid arthritis or osteoarthrosis, it was found that although the drug produced satisfactory analgesia in 64% of patients, the incidence of side-effects was high (57% of patients): most were symptoms of salicylism and probably related to the high plasma salicylate levels achieved. In a second open study, 20 patients with osteoarthrosis were treated for 4 weeks with 250 mg diflunisal twice daily and then crossed over to salsalate (3 g daily) for a further 2 weeks. The results of subjective assessments of pain relief showed that both drugs produced satisfactory analgesia, and neither was associated with a significant level of gastro-intestinal bleeding. During the diflunisal treatment period there were no reports of salicylism, and plasma salicylate levels were very much lower than those measured after salsalate. The pain relieving effects of both drugs, assessed from patient preference for one or the other treatment, were unrelated to the plasma salicylate levels and it is suggested that plasma levels may have more relationship to the incidence of side-effects than with therapeutic effects.

Topics: Analgesics; Aspirin; Biphenyl Compounds; Clinical Trials as Topic; Humans; Occult Blood; Osteoarthritis; Pain; Salicylates; Time Factors

Thirty patients with osteoarthritis of knees or hips took part in a double-blind randomized 12-week inter-group clinical trial of diflunisal 250 mg to 375 mg twice daily against aspirin 500 mg to 750 mg four times daily using the double-placebo technique. Changes were assessed in weight-bearing pain and night pain, stiffness after rest, a specified activity, and overall judgements by patient and physician, all graded on a five-point scale. Intermalleolar distance or knee flexion were measured. Side-effects and safety tests were monitored. Diflunisal produced statistically significant responses for all the criteria, when numbers of patients better or worse after 12 weeks were compared using the sign test. Neither the figures for aspirin alone, nor a comparison between the two treatment groups, reached statistical significance. Side-effects and especially dropouts were less on diflunisal. Nine patients on diflunisal but only two on aspirin wanted to continue treatment beyond 12 weeks, though still 'blind' when deciding this. Diflunisal may be a useful, less toxic and longer acting alternative to aspirin in the management of osteoarthritis.

Topics: Abdomen; Aspirin; Clinical Trials as Topic; Dizziness; Double-Blind Method; Drug Administration Schedule; Edema; Humans; Osteoarthritis; Pain; Salicylates; Time Factors

In this two-week study, Benoral tablets, at a 4.5 g daily dosage were compared with a matching placebo in 20 patients suffering from sports injury. Four assessments were made: pain at rest, pain on movement, tenderness and soft tissue swelling. In each case the active treatment group (benorylate) was statistically greater than that in the placebo group at one week and after two weeks' treatment.

Topics: Athletic Injuries; Bursitis; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Pain; Placebos; Salicylates; Synovitis; Tablets

Selected patients with extraction wounds served to experiment with Apernyl-styli of Bayer. Contralateral alveoli were used as controls. 10 days following operation biopsies were taken from treated and untreated alveoli. Histologically, a morphometric study was made, and clinically healing was judged by the frequency of complications and the initial physiologic pain. The results show that Apernyl does not influence histological healing, positively or negatively. Thus, the results obtained by Nordenram and Band (1970) and Satoh et al. (1973) could be confirmed. Clinically, there were significanlty less p.o. complications in patients with Apernyl prophylaxis; 2 of 51 treated alveoli compared to 8 of 45 untreated ones. Pain was significantly reduced: 17 of the 19 patients complained of pain in the untreated half of the jaw, while only 4 suffered pain on the treated side. This confirms the findings of Neuner and Panzera and Neuner and Schegg (1972 and 1969 resp.).

Topics: Alveolar Process; Blood Coagulation; Drug Evaluation; Dry Socket; Granulation Tissue; Humans; Osteogenesis; Pain; Salicylates; Tooth Extraction; Wound Healing

A single-blind non-crossover method for assessing the potential effectiveness of antirheumatic drugs has been described. The method employs entirely subjective indices and incorporates a daily pain chart for measuring the pain response over the duration of the trial. In addition, the mean number of days withdrawn and patients' satisfaction rating are measured. The statistical method can correct for initial imbalances between groups and allows for the valid comparison of drugs from separate trials. Ten antirheumatic medications were evaluated using this technique in 684 patients with rheumatoid arthritis, and the results are in agreement with those of previous studies using standard clinical methods. The new method is simple, rapid in performance, economical in terms of cost and time, and has been shown to be sensitive and reproducible. The results indicate that there are no significant differences in efficacy between the currently available non-steroidal, anti-inflammatory analgesic drugs, in the treatment of rheumatoid arthritis.

Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Flurbiprofen; Humans; Ibuprofen; Indomethacin; Ketoprofen; Mefenamic Acid; Pain; Phenylacetates; Placebos; Prednisone; Salicylates

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Drug Combinations; Female; Gels; Heparin; Humans; Hyperemia; Male; Middle Aged; Nicotinic Acids; Osteoarthritis; Pain; Regional Blood Flow; Salicylates

Benorylate and ibuprofen appear to be useful drugs for pain relief in rheumatoid arthritis but benorylate would appear to have a slightly better effect on the pain score and it improved the grip strength more than the moderate doses of ibuprofen. It could be a most useful drug when gastric problems limit the dose of aspirin or of other analgesics.

Topics: Arthritis, Rheumatoid; Clinical Trials as Topic; Hand; Humans; Ibuprofen; Pain; Propionates; Salicylates

Topics: Administration, Oral; Analgesics; Aspirin; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Clinical Trials as Topic; Codeine; Dextropropoxyphene; Drug Evaluation; Hemophilia A; Humans; Pain; Pentazocine; Prednisone; Salicylates

Topics: Clinical Trials as Topic; Codeine; Diazepam; Disability Evaluation; Follow-Up Studies; Humans; Male; Methylprednisolone; Pain; Placebos; Salicylates; Surveys and Questionnaires; Time Factors; Vasectomy

Topics: Acetanilides; Acetates; Analgesics; Arthritis, Rheumatoid; Aspirin; Blood Sedimentation; Clinical Trials as Topic; Female; Humans; Inflammation; Male; Middle Aged; Pain; Salicylates

Topics: Adult; Aged; Choline; Clinical Trials as Topic; Dry Socket; Female; Gels; Humans; Male; Middle Aged; Mouth Diseases; Pain; Salicylates; Stomatitis, Aphthous; Stomatitis, Denture

In a double-blind between-patient study of aspirin and benorylate carried out in 72 outpatients with rheumatoid arthritis, benorylate 4 g twice daily was shown to be an effective analgesic and anti-inflammatory drug, its effects being indistinguishable from those of aspirin 1.2 g four times daily. Compared with the pretreatment values both drugs produced a statistically significant improvement (P < 0.01) in functional grade, overall pain, articular index, and grip strength at the end of the first and second weeks. The overall incidence of side effects was less with benorylate, though this difference was not significant at the 5% level.

Topics: Adolescent; Adult; Aged; Analgesics; Aniline Compounds; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Aspirin; Clinical Trials as Topic; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Movement; Pain; Phenols; Physical Examination; Salicylates; Tinnitus

Topics: Action Potentials; Adult; Aged; Analgesics; Arthritis, Rheumatoid; Audiometry; Clinical Trials as Topic; Electromyography; Female; Humans; Irritants; Male; Methane; Middle Aged; Muscle Cramp; Osteoarthritis; Pain; Placebos; Salicylates; Sensation

Topics: Acetaminophen; Choline; Clinical Trials as Topic; Ear Diseases; Humans; Pain; Salicylates

Topics: Adolescent; Adult; Aged; Analgesics; Clinical Trials as Topic; Codeine; Dentistry, Operative; Humans; Middle Aged; Pain; Salicylates

Topics: Adolescent; Adult; Aged; Clinical Trials as Topic; Female; Gels; Humans; Male; Middle Aged; Mouth; Mouth Diseases; Pain; Salicylates

Topics: Arthritis, Rheumatoid; Circadian Rhythm; Clinical Trials as Topic; Finger Joint; Fingers; Humans; Manometry; Methadone; Methylprednisolone; Movement; Pain; Placebos; Polymers; Salicylates

Topics: Acute Disease; Arthritis, Rheumatoid; Bone Diseases; Clinical Trials as Topic; Drug Synergism; Humans; Osteoarthritis; Osteochondritis; Osteoporosis; Pain; Penicillins; Placebos; Pleurisy; Prednisolone; Rheumatic Diseases; Rheumatic Fever; Salicylates; Spondylitis

Topics: Analgesia; Analgesics; Aspirin; Cyclazocine; Humans; Morphine; Narcotic Antagonists; Pain; Phenacetin; Placebos; Salicylates

Pain is a serious adverse event which frequently accompanies hematopoietic stem cell transplantation (HSCT). The safety and efficacy of NSAIDS during HSCT is currently unknown. Salsalate is a platelet-sparing NSAID with a favorable toxicity profile compared with other NSAIDS. We report the safety and efficacy of salsalate for different types of pain during SCT.. We conducted a retrospective study of SCT recipients empirically treated with salsalate for > 48 h. Pain scores were assessed using the verbal rating scale for pain. A subset analysis of patients who received > 7 days of salsalate during periods of pancytopenia, mucositis, and other end-organ toxicities is included.. Sixty-four patients, 42 auto- and 22 allografts, were identified. Reason for use: vertebral-related pain (30%), musculoskeletal (30%), and cytokine inflammatory pain syndromes (24%). Median dose 1500 mg/day, number of treatment days = 5, started on day+5 post-HSCT. Pain resolved/improved to pain score < 4 in 76% and stable in 15%. Forty-four patients (28-auto and 16 allografts) received > 7-day salsalate. Median WBC and platelet nadir were < 0.1 and 10,000 cells/ml respectively.. pain was improved or eradicated in 64% and stable in 32%.. LFT elevation (n = 2), elevated serum creatinine (n = 2), and minor bleed (n = 5-nose, gums, and urine). Salsalate discontinuation (n = 6): ineffective (n = 1), the liver (n = 1), the kidney (n = 1), > 5 platelet transfusions (n = 1), and vomiting (n = 2). There was no treatment related mortality. Salsalate was well tolerated, safe, and beneficial for several different types of pain during HSCT.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Mucositis; Pain; Retrospective Studies; Salicylates; Transplantation Conditioning; Transplantation, Homologous; Young Adult

Salicytamide is a new drug developed through molecular modelling and rational drug design by the molecular association of paracetamol and salicylic acid. This study was conducted to assess the acute oral toxicity, antinociceptive, and antioedematogenic properties of salicytamide. Acute toxicity was based on the OECD 423 guidelines. Antinociceptive properties were investigated using the writhing, hot plate and formalin tests in Swiss mice. Antioedematogenic properties were evaluated using the carrageenan-induced paw oedema model and croton oil-induced dermatitis in Wistar rats. Salicytamide did not promote behavioural changes or animal deaths during acute oral toxicity evaluation. Furthermore, salicytamide exhibited peripheral antinociceptive activity as evidenced by the reduction in writhing behaviour (ED50 = 4.95 mg/kg) and licking time in the formalin test's inflammatory phase. Also, salicytamide elicited central antinociceptive activity on both hot plate test and formalin test's neurogenic phase. Additionally, salicytamide was effective in reducing carrageenan or croton oil-induced oedema formation. Overall, we have shown that salicytamide, proposed here as a new NSAID candidate, did not induce oral acute toxicity and elicited both peripheral antinociceptive effects (about 10-25 times more potent than its precursors in the writhing test) and antioedematogenic properties. Salicytamide also presented central antinociceptive activity, which seems to be mediated through opioid-independent mechanisms. These findings reveal salicytamide as a promising antinociceptive/antioedematogenic drug candidate.

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Design; Edema; Mice; Nociception; Pain; Rats, Wistar; Salicylates

The main objective of this study was to develop reversed hexagonal (H

Topics: Administration, Cutaneous; Analgesics; Animals; Anti-Inflammatory Agents; Biological Availability; Drug Delivery Systems; Edema; Fatty Alcohols; Female; Liquid Crystals; Male; Mice; Pain; Rats, Wistar; Salicylates; Skin; Skin Absorption; Skin Irritancy Tests

The mechanism(s) by which cells can sense exogenous oxidants that may contribute to intracellular oxidative/nitrosative stress is not clear. The objective of this study was to determine how cells might respond to exogenous oxidants to potentially initiate, propagate and/or maintain inflammation associated with many human diseases through NF-κB activation. First, we used HEK-Blue cells that are stably transfected with mouse toll-like receptor 4 (mTLR4) or mouse TLR2. These cells also express optimized secreted embryonic alkaline phosphatase (SEAP) reporter gene under the control of a promoter inducible by NF-κB transcription factor. These cells were challenged with their respective receptor-specific ligands, different pro-oxidants and/or inhibitors that act at different levels of the receptor signaling pathways. A neutralizing antibody directed against TLR4 inhibited responses to both TLR4-specific agonist and a prooxidant, which confirmed that both agents act through TLR4. We used the level of SEAP released into the culture media due to NF-κB activation as a measure of TLR4 or TLR2 stimulation. Pro-oxidants evoked increased release of SEAP from HEK-Blue mTLR4 cells at a much lower concentration compared with release from the HEK-Blue mTLR2 cells. Specific TLR4 signaling pathway inhibitors and oxidant scavengers (anti-oxidants) significantly attenuated oxidant-induced SEAP release by TLR4 stimulation. Furthermore, a novel pro-oxidant that decays to produce the same reactants as activated phagocytes induced inflammatory pain responses in the mouse orofacial region with increased TLR4 expression, and IL-1β and TNFα tissue levels. EUK-134, a synthetic serum-stable scavenger of oxidative species decreased these effects. Our data provide in vitro and related in vivo evidence that exogenous oxidants can induce and maintain inflammation by acting mainly through a TLR4-dependent pathway, with implications in many chronic human ailments.

Topics: Alkaline Phosphatase; Animals; Antioxidants; Cell Engineering; Cell Survival; Chromates; Gene Expression Regulation; HEK293 Cells; Humans; Interleukin-1beta; Male; Mice; NF-kappa B; Organometallic Compounds; Oxidants; Oxidative Stress; Pain; Pain Threshold; Peroxides; Reactive Nitrogen Species; Reactive Oxygen Species; Salicylates; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4

To study transdermal absorption characteristics of eugenol in compound Nanxing pain-relieving cataplasm, and discuss the effect of gaultherolin on the transdermal absorption of the cataplasm.. The improved franz diffusing cell was adopted with hairless mice skins as transdermal carriers. The content of eugenol in receptor liquid, skins and cataplasm were analyzed by HPLC and compared with the cataplasm without gaultherolin.. The penetration rates of eugenol of cataplasms with and without gaultherolin were 13.18 and 9.58 microg x cm(-2) x h(-1), with the retention amount in skins of (185.02 +/- 19.23) and (160.23 +/- 16.54) microg x g(-1) and the retention amount in cataplasms was (1.96 +/- 0.12) and (1.71 +/- 0.15) mg, respectively.. Eugenol in compound Nanxing pain-relieving cataplasm has good pereutaoeous permeation. Gaultherolin in the cataplasm prescription can promote the absorption of eugenol.

Topics: Analgesics; Animals; Chemistry, Pharmaceutical; Drugs, Chinese Herbal; Mice; Pain; Salicylates; Skin; Skin Absorption; Time Factors

Nitrous oxide (N2O, laughing gas) has been used as an anaesthetic and analgesic for almost two centuries, but its cellular targets remain unclear. Here, we present a molecular mechanism of nitrous oxide's selective inhibition of CaV3.2 low-voltage-activated (T-type) calcium channels in pain pathways. Using site-directed mutagenesis and metal chelators such as diethylenetriamine pentaacetic acid and deferoxamine, we reveal that a unique histidine at position 191 of CaV3.2 participates in a critical metal binding site, which may in turn interact with N2O to produce reactive oxygen species (ROS). These free radicals are then likely to oxidize H191 of CaV3.2 in a localized metal-catalysed oxidation reaction. Evidence of hydrogen peroxide and free radical intermediates is given in that N2O inhibition of CaV3.2 channels is attenuated when H2O2 is neutralized by catalase. We also use the adrenochrome test as an indicator of ROS in vitro in the presence of N2O and iron. Ensuing in vivo studies indicate that mice lacking CaV3.2 channels display decreased analgesia to N2O in response to formalin-induced inflammatory pain. Furthermore, a superoxide dismutase and catalase mimetic, EUK-134, diminished pain responses to formalin in wild-type mice, but EUK-134 and N2O analgesia were not additive. This suggests that reduced ROS levels led to decreased inflammation, but without the presence of ROS, N2O was not able to provide additional analgesia. These findings reveal a novel mechanism of interaction between N2O and ion channels, furthering our understanding of this widely used analgesic in pain processing.

Topics: Adrenochrome; Analgesics, Non-Narcotic; Animals; Calcium Channel Blockers; Calcium Channels, T-Type; Catalase; Chelating Agents; Deferoxamine; Disease Models, Animal; Female; Ganglia, Spinal; HEK293 Cells; Histidine; Humans; Hydrogen Peroxide; Male; Membrane Potentials; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutagenesis, Site-Directed; Nitrous Oxide; Organometallic Compounds; Oxidation-Reduction; Pain; Pentetic Acid; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Salicylates; Signal Transduction; Time Factors; Transfection

Topics: Age Factors; Anti-Inflammatory Agents, Non-Steroidal; Choline; Drug Combinations; Female; Gels; Humans; Infant; Male; Pain; Poisoning; Salicylates; Tooth Eruption

Siegesbeckia orientalis has been traditionally used as a topical anti-inflammatory and analgesic agent.. Current study was designed to explore the topical anti-inflammatory and analgesic effects of a constituent isolated from Siegesbeckia orientalis (Compositae), in order to validate its folk use.. Kirenol was isolated from ethanolic extract of Siegesbeckia orientalis. Several topical formulations containing kirenol were investigated for anti-inflammatory and analgesic activities in rat. The effects were studied using carrageenan-induced rat acute inflammation model, complete Freund's adjuvant (CFA)-induced chronic inflammation and formalin test in rats. Piroxicam gel and methyl salicylate ointment were studied as positive control for anti-inflammatory and analgesic activity, respectively.. The anti-inflammatory effect of kirenol 0.4-0.5% (w/w) was similar to the effect of piroxicam gel 4h after carrageenan injection. The analgesic activity of topical preparation with more than 0.4% (w/w) was observed in the late phase. These effects may be due, at least in part, to the pro-inflammatory cytokine production of IL-1β and TNF-α. The administration of kirenol cream at the dose of 0.3, 0.4 and 0.5% (w/w) significantly inhibited the development of joint swelling induced by CFA, which was auxiliary supported by histopathological studies.. Kirenol has demonstrated its significant potential to be further investigated for its discovery as a new lead compound for management of topical pain and inflammation, although further pharmacological research is necessary to fully understand its mechanism of action. It also supports the potential beneficial effect of topically administered Siegesbeckia orientalis in inflammatory diseases.

Topics: Administration, Topical; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Asteraceae; Carrageenan; Diterpenes; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Ethanol; Formaldehyde; Freund's Adjuvant; Inflammation; Inflammation Mediators; Interleukin-1beta; Pain; Piroxicam; Plant Components, Aerial; Plants, Medicinal; Rats; Salicylates; Solvents; Time Factors; Tumor Necrosis Factor-alpha

We investigated the antinociceptive and nerve excitability effects of the N-salicyloyltryptamine (NST) NST-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg (i.p.) were administered (i.p.). This effect was not antagonized by naloxone (1.5 mg/kg, i.p.). NST inhibited the licking response of the injected paw when 100 and 200 mg/kg were administered (i.p.) to mice in the first and second phases of the formalin test. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and showed that NST (3.57 mM) significantly reduced (29.2%) amplitude of the compound action potential (CAP) suggesting a sodium channel effect induced by NST. Our results demonstrated an antinociceptive activity of the NST that could be, at least in part, associated to the reduction of the action potential amplitude. NST might represent an important tool for pain management.

Topics: Acetic Acid; Action Potentials; Analgesics; Animals; Behavior, Animal; Biological Assay; Diazepam; Electrophysiological Phenomena; Formaldehyde; Indomethacin; Male; Mice; Pain; Rotarod Performance Test; Salicylates; Time Factors; Tryptamines

Diabetic neuropathy is manifested either by loss of nociception (painless syndrome) or by mechanical hyperalgesia and tactile allodynia (pain in response to nonpainful stimuli). While therapies with vasodilators or neurotrophins reverse some functional and metabolic abnormalities in diabetic nerves, they only partially ameliorate neuropathic pain. The reported link between nociception and targets of the anti-inflammatory drug sulfasalazine prompted us to investigate its effect on neuropathic pain in diabetes.. We examined the effects of sulfasalazine, salicylates, and the poly(ADP-ribose) polymerase-1 inhibitor PJ34 on altered nociception in streptozotocin-induced diabetic rats. We also evaluated the levels of sulfasalazine targets in sciatic nerves and dorsal root ganglia (DRG) of treated animals. Finally, we analyzed the development of tactile allodynia in diabetic mice lacking expression of the sulfasalazine target nuclear factor-kappaB (NF-kappaB) p50.. Sulfasalazine completely blocked the development of tactile allodynia in diabetic rats, whereas relatively minor effects were observed with other salicylates and PJ34. Along with the behavioral findings, sciatic nerves and DRG from sulfasalazine-treated diabetic rats displayed a decrease in NF-kappaB p50 expression compared with untreated diabetic animals. Importantly, the absence of tactile allodynia in diabetic NF-kappaB p50(-/-) mice supported a role for NF-kappaB in diabetic neuropathy. Sulfasalazine treatment also increased inosine levels in sciatic nerves of diabetic rats.. The complete inhibition of tactile allodynia in experimental diabetes by sulfasalazine may stem from its ability to regulate both NF-kappaB and inosine. Sulfasalazine might be useful in the treatment of nociceptive alterations in diabetic patients.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Body Weight; Chromatography, High Pressure Liquid; Diabetes Mellitus, Experimental; Ganglia, Spinal; Immunoblotting; Inosine; NF-kappa B p50 Subunit; Pain; Pain Measurement; Phenanthrenes; Rats; Salicylates; Sciatic Nerve; Sulfasalazine; Tandem Mass Spectrometry

The analgesic and anti-inflammatory activities of a salicylate derivatives fraction (SDF) isolated from Gaultheria yunnanensis (FRANCH.) REHDER and the mechanisms of actions were investigated in the present study. The major constituent of SDF, which represented around 50% of this fraction, was a methyl salicylate diglycoside named gaultherin. SDF showed a significant inhibition on the hind paw edema in rats (200, 400 mg/kg body wt., p.o.) and ear swelling in mice (200, 400, 800 mg/kg body wt., p.o.) caused by carrageenin and croton oil, respectively. In addition, SDF (400, 800 mg/kg body wt., p.o.) inhibited only the second phase (inflammatory) in the formalin test, and showed no effect in the hot-plate test in mice. The antinociceptive activity of SDF was predominantly peripheral and independent of the opioid system. These findings demonstrate that SDF from Gaultheria yunnanensis (FRANCH.) REHDER possesses analgesic and anti-inflammatory activities, which may be mediated, at least partly, through the suppression of inflammatory mediators or their release suggested by the animal experiment. The observed effects of SDF are probably due to the presence of high content of salicylate derivatives (80%), including gaultherin, MSTG-A and MSTG-B.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carrageenan; Croton Oil; Disaccharides; Dose-Response Relationship, Drug; Ear; Edema; Female; Formaldehyde; Gaultheria; Glycosides; Hindlimb; Indomethacin; Male; Mice; Mice, Inbred Strains; Molecular Structure; Pain; Rats; Rats, Wistar; Salicylates

Pain is a multistep process that originates in the peripheral nervous system at the site of injury, is transmitted and processed within the central nervous system, and is perceived at the level of the cerebral cortex. Each of these steps in pain transmission is subject to intervention, with the possibility of reducing or blocking the nociceptive information to result in decreased pain. Based on knowledge of pain processes, dentists can use analgesic strategies to prevent or reduce pain.

Topics: Analgesics; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Cerebral Cortex; Facial Pain; Humans; Nerve Fibers; Neurogenic Inflammation; Nociceptors; Oral Surgical Procedures; Pain; Pain, Postoperative; Salicylates; Trigeminal Caudal Nucleus

This work includes the synthesis of 15 final compounds (6a-h and 7b-h) as prodrugs of 5-ASA in the form of the acid itself, esters and amides linked by an amide linkage through a spacer to the endocyclic ring N of nicotinamide. Also, 15 new intermediate compounds were prepared. The target compounds (6b, 6f, 7b, and 7e-h) revealed potent analgesic and anti-inflammatory activities in comparison to sulfasalazine and 5-ASA. In addition, ulcerogenicity, LD50, in vivo and in vitro metabolism of compound 7f were determined.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carrageenan; Drug Stability; Edema; Feces; Gastrointestinal Contents; Hydrogen-Ion Concentration; Lethal Dose 50; Magnetic Resonance Spectroscopy; Male; Mesalamine; Mice; Pain; Prodrugs; Rats; Salicylamides; Salicylates; Stomach Ulcer; Streptococcus pyogenes; Structure-Activity Relationship

Protein kinase C (PKC) is able to phosphorylate several cellular components that serve as key regulatory components in signal transduction pathways of nociceptor excitation and sensitisation. Therefore, the present study attempted to assess some of the mechanisms involved in the overt nociception elicited by peripheral administration of the PKC activator, phorbol 12-myristate 13-acetate (PMA), in mice. The intraplantar (i.pl.) injection of PMA (16-1600 pmol/paw), but not its inactive analogue alpha-PMA, produced a long-lasting overt nociception (up to 45 min), as well as the activation of PKCalpha and PKCepsilon isoforms in treated paws. Indeed, the local administration of the PKC inhibitor GF109203X completely blocked PMA-induced nociception. The blockade of NK1, CGRP, NMDA, beta1-adrenergic, B2 or TRPV1 receptors with selective antagonists partially decreased PMA-induced nociception. Similarly, COX-1, COX-2, MEK or p38 MAP kinase inhibitors reduced the nociceptive effect produced by PMA. Notably, the nociceptive effect promoted by PMA was diminished in animals treated with an antagonist of IL-1beta receptor or with antibodies against TNFalpha, NGF or BDNF, but not against GDNF. Finally, mast cells as well as capsaicin-sensitive and sympathetic fibres, but not neutrophil influx, mediated the nociceptive effect produced by PMA. Collectively, the results of the present study have shown that PMA injection into the mouse paw results in PKC activation as well as a relatively delayed, but long-lasting, overt nociceptive behaviour in mice. Moreover, these results demonstrate that PKC activation exerts a critical role in modulating the excitability of sensory neurons.

Topics: Adrenergic beta-Antagonists; Analgesics; Animals; Antibodies; Behavior, Animal; Blotting, Western; Bradykinin; Calcitonin Gene-Related Peptide; Capsaicin; Chelating Agents; Dipeptides; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drug Interactions; Egtazic Acid; Enzyme Activation; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Extracellular Signal-Regulated MAP Kinases; Guanethidine; Indoles; Male; Mice; Nociceptors; Pain; Pain Measurement; Peptide Fragments; Propranolol; Protein Kinase C; Ruthenium Red; Salicylates; Sympatholytics; Tetradecanoylphorbol Acetate; Time Factors

The possibility of introducing eye-wiping test as a model of acute pain was examined in rat, and it was compared with the well-known hot plate test. One drop of NaCl 5 M was placed into the animal eye, and the number of eye wipes with the ipsilateral forelimb was counted during 30 s. The withdrawal latency in hot plate test was also examined. Afterward, animals were treated with morphine (1, 2, 4, 6, 8 or 10 mg/kg), imipramine (25 mg/kg), sodium salicylate (250 mg/kg) or saline (i.p). After 30 min, the animals were tested again with eye-wiping and hot plate tests. Our results showed that morphine injection dose dependently decreased the number of eye wipes and increased the response latency to hot plate tests. There was a good correlation between the analgesic effects of morphine on responses to both tests, however, morphine produced more pain relief in eye-wiping test. Imipramine significantly decreased the number of eye wipes and increased the response latency to hot plate test, while sodium salicylate and saline injection did not. It may be concluded that the eye-wiping test can be used as a reliable method in trigeminal pain studies, which is sensitive to opioid and tricyclic antidepressant in rat.

Topics: Analgesics, Opioid; Animals; Antidepressive Agents; Behavior, Animal; Cornea; Data Interpretation, Statistical; Disease Models, Animal; Eye; Imipramine; Irritants; Male; Morphine; Pain; Pain Measurement; Rats; Rats, Wistar; Reaction Time; Salicylates; Sodium Chloride; Trigeminal Neuralgia

Topics: Administration, Topical; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Chemotherapy, Adjuvant; Humans; Pain; Salicylates

Topics: Administration, Topical; Analgesics, Non-Narcotic; Capsaicin; Humans; Ointments; Pain; Salicylates

Cutaneous lichenoid eruptions can arise as a result of exogenous compound exposures. Pharmaceutical drugs, industrial compounds, and inhaled particles have been implicated as causative agents. To date, there have been no recorded cases of lichenoid drug eruptions (LDEs) caused by clinical use of the nonsteroidal anti-inflammatory drug salsalate. We describe a patient who experienced a lichenoid eruption after the initiation of salsalate for relief of arthritic pain. This eruption emerged after 1 month of therapy with salsalate, persisted for as long as salsalate was administered, and cleared within 3 weeks of discontinuing the medication. LDEs can clinically and histologically resemble idiopathic or classic lichen planus. Integrating drug history, clinical morphology, clinical distribution, and histopathology can aid in the differentiation. As in our patient's case, curative treatment for LDE requires discontinuation of the drug.

Topics: Administration, Topical; Aged; Aged, 80 and over; Arthritis; Drug Eruptions; Humans; Lichen Planus; Male; Pain; Salicylates; Treatment Outcome

Topics: Age Factors; Aged; Anti-Inflammatory Agents, Non-Steroidal; Choline; Chronic Disease; Humans; Pain; Salicylates; Time Factors

Topics: Administration, Cutaneous; Analgesics; Copper; Gels; Hip Joint; Humans; Knee Joint; Osteoarthritis; Osteoarthritis, Hip; Pain; Salicylates

Topics: Adult; Bone Neoplasms; Hip; Humans; Male; Osteoma, Osteoid; Pain; Pain Measurement; Salicylates; Tomography, X-Ray Computed

The mechanism by which dietary pepper causes dyspepsia and epigastric pain is poorly understood, as is the ability of bismuth subsalicylate (BSS) to relieve these symptoms.. To investigate the ability of black pepper, red pepper and BSS to affect gastric surface hydrophobicity and induce/relieve visceral pain in rat model systems.. Fasted rats were administered intragastrically Vivonex containing varying concentrations of either black or red pepper (0-200 mg/mL) and gastric contact angles were read after 1-24 h. Some rats were post-treated with BSS (2.0-17.5 mg/mL) and contact angles were read after 2-18 h. To study pain sensitivity in rats treated with pepper/BSS, we compared tail-flick latencies after the application of radiant heat.. Both black and red pepper rapidly (< 1 h) induced a decrease in gastric surface hydrophobicity in a dose-dependent fashion. This spice-induced increase in surface wettability was long-lasting, could be enhanced in the presence of ethanol and reversed by post-treating the rats with BSS. Both black and red pepper induced an increase in pain sensitivity, consistent with the presence of gastric pain, which could also be reversed by post-treating the rats with BSS.. Both black and red pepper may induce epigastric pain by removing the stomach's hydrophobic lining and activating intramucosal pain receptors. BSS may provide relief from postprandial dyspepsia by restoring the stomach's non-wettable properties.

Topics: Animals; Bismuth; Chemical Phenomena; Chemistry, Physical; Diet; Dose-Response Relationship, Drug; Gastric Acid; Gastric Mucosa; Male; Organometallic Compounds; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Regression Analysis; Salicylates; Spices; Stomach Diseases; Surface Properties

Topics: Adult; Analgesics; Anti-Inflammatory Agents; Dermatitis, Allergic Contact; Female; Humans; Pain; Patch Tests; Salicylates; Salicylic Acid

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Capsaicin; Humans; Irritants; Liniments; Ointments; Pain; Palliative Care; Pharmacopoeias, Homeopathic as Topic; Salicylates

Topics: Bismuth; Colon; HIV Infections; Humans; Male; Middle Aged; Organometallic Compounds; Pain; Radiography; Salicylates; Self Medication

The ability of caffeine to potentiate the analgesic effect of aspirin was studied in the pain-induced functional impairment model in the rat. Female Wistar rats received an intra-articular injection of 30% uric acid in the right hind limb, inducing its dysfunction. Once the dysfunction was complete, animals received aspirin oral doses of 0, 0.55, 0.98, and 1.74 mmol/kg with and without 0.17 mmol/kg of caffeine, and the recovery of functionality over time was considered as an expression of analgesia. Blood samples were drawn simultaneously with hind limb functionality determinations, and plasma concentrations of aspirin, salicylic acid, and gentisic acid were measured by high-performance liquid chromatography. Aspirin induced a dose-dependent analgesic effect. Caffeine alone was ineffective. However, caffeine significantly increased the analgesic effect of aspirin at all doses, without modifying aspirin, salicylic acid, or gentisic acid plasma levels. It is concluded that caffeine potentiates the analgesic effect of aspirin by a pharmacodynamic, but not by a pharmacokinetic mechanism.

Topics: Animals; Aspirin; Caffeine; Drug Synergism; Female; Gentisates; Hindlimb; Hydroxybenzoates; Pain; Rats; Rats, Wistar; Salicylates; Salicylic Acid

Administration of acetylsalicylic acid (aspirin) in the dog may cause gastric mucosal damage. Enteric-coated tablets protect the canine stomach during oral aspirin medication. A therapeutic plasma salicylate concentration can be attained using enteric-coated aspirin tablets at a dosage of 25 mg/kg TID. In a series 4 of experiments using adult beagle and large mixed breed dogs and two types enteric-coated tablets, the influence of food intake on the plasma salicylate concentration was studied. Tablets were administered with 8h intervals and food intake was either once daily or three time daily with 8h intervals. Plasma salicylate concentrations were also studied during fasting. It is concluded that, when using enteric-coated tablets, the plasma salicylate concentration in the dog after oral medication is strongly influenced by the aspirin dosage, the tablet type and the feeding pattern. Large enteric-coated tablets may accumulate in the stomach over several days and are not suitable for use in the dog. The gastric accumulation is caused by the enteric-coating of the large tablets and not by the aspirin medication.

Topics: Animals; Aspirin; Dog Diseases; Dogs; Food; Pain; Salicylates; Tablets; Time Factors

Topics: Animals; Animals, Domestic; Anti-Inflammatory Agents, Non-Steroidal; Half-Life; Pain; Salicylates; Species Specificity

Topics: Analgesia; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Child; Female; Humans; Infant; Ketorolac; Pain; Pain, Postoperative; Premedication; Propionates; Salicylates; Tolmetin

Topics: Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Child, Preschool; Diet; Female; Fever; Health Education; Humans; Hygiene; Male; Otorhinolaryngologic Diseases; Pain; Parents; Pediatrics; Professional-Family Relations; Salicylates; Seizures; Social Class; Thermometers; Time Factors

1. The effects of paracetamol and lysine acetylsalicylate (L-AS) on high-threshold mechanonociceptors have been investigated by recording neural activity from the inflamed ankle joint in anaesthetized rats with mild adjuvant-induced monoarthritis. 2. Paracetamol (50 mg kg-1, i.v.) and L-AS (100 mg kg-1, i.v., equivalent to 50 mg kg-1 aspirin) both caused a maximal reduction of about 40% in mechanically-evoked discharge and of 30% in ongoing (spontaneous) activity by about 15 min after the injection: a second dose of either drug did not have any significant additional effect on discharge. 3. The prostanoid IP receptor agonist, cicaprost (0.1-0.5 micrograms), increased both mechanically-evoked and ongoing discharge to pre-paracetamol levels when injected close-arterially 30-50 min after paracetamol, whereas prostaglandin E2 (PGE2) was relatively ineffective at restoring activity. 4. The results suggest that prostacyclin (PGI2) contributes to the sensitization of high-threshold joint mechanonociceptors in adjuvant-induced monoarthritis, and that paracetamol and L-AS both act to reduce discharge by inhibiting the synthesis of prostacyclin in the joint capsule. 5. Paracetamol has a direct peripheral action affecting joint capsule mechanonociceptors in rat adjuvant-induced arthritis which is very similar to that of the soluble aspirin preparation, L-AS. These findings, together with the existing literature concerning the anti-arthritic effects of paracetamol, are relevant to the treatment of chronic inflammatory disorders such as rheumatoid arthritis.

Topics: Acetaminophen; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Aspirin; Epoprostenol; Lysine; Male; Mechanoreceptors; Neural Conduction; Neurons; Nociceptors; Pain; Rats; Rats, Inbred Strains; Salicylates; Sensory Thresholds; Tarsus, Animal

The analgesic response-serum concentration relationship (pharmacodynamics) of a representative nonsteroidal antiinflammatory drug, diflunisal, was examined after an acute dose in adjuvant arthritic and control rats. The analgesic response was 2-fold higher in the arthritic animals compared to controls. In parallel with this, there was a 2-fold increase in the serum free concentrations of diflunisal in the arthritic rats. Thus, the increase in diflunisal analgesic response in arthritis may be attributed to pharmacokinetic perturbations, resulting from alterations in serum protein binding and not to changes in drug pharmacodynamics. Endogenous binding inhibitors in adjuvant arthritis may contribute to the observed decreased in diflunisal protein binding.

Topics: Animals; Arthritis; Arthritis, Experimental; Diflunisal; Dose-Response Relationship, Drug; Injections, Intravenous; Male; Metabolic Clearance Rate; Pain; Protein Binding; Rats; Rats, Inbred Lew; Salicylates; Sensory Thresholds

Topics: Acetaminophen; Analgesics; Dipyrone; Dose-Response Relationship, Drug; Drug Combinations; Humans; Pain; Risk; Salicylates; Self Medication

Topics: Adult; Anti-Inflammatory Agents; Female; Humans; Imidazoles; Male; Middle Aged; Muscles; Pain; Pindolol; Salicylates; Wounds and Injuries

Topics: Adult; Aged; Anti-Inflammatory Agents; Female; Humans; Imidazoles; Male; Middle Aged; Osteoarthritis; Pain; Salicylates

Topics: Acetaminophen; Analgesics; Dental Care; Drug Combinations; Humans; Pain; Pain, Postoperative; Pyrazoles; Pyrazolones; Salicylates

In this paper several issues are examined that arise from conducting randomized clinical trials in a family practice setting. The distinctive research tradition in family practice involves a patient's primary care physician performing an experimental investigation that usually, though not invariably, is focused on common health problems. Representative clinical trials are presented as examples that illustrate two ethical difficulties evoked by such research: a potential violation of the primary care physician's therapeutic imperative to provide the best possible treatment for his or her patient, and the likelihood that the type of physician-patient relationship fostered in family practice significantly diminishes the capacity of the patient to give true informed consent. In an attempt to resolve these ethical difficulties, a model of moral reasoning is presented that is based on easily understood ethical principles and is applicable to actual clinical decision making. Using that model, a tentative set of rules or guidelines is offered for implementing clinical trials in family medicine.

Topics: Clinical Trials as Topic; Conflict, Psychological; Ethics, Medical; Family Practice; Female; Humans; Informed Consent; Models, Theoretical; Morals; Pain; Physician-Patient Relations; Random Allocation; Recurrence; Research Design; Salicylates; Urinary Tract Infections

In an open study in patients with tumour-induced pain the analgetic effects of the prostaglandin-inhibiting compound diflunisal and the centrally-acting analgetic tilidine N were compared. A dosage of 1 g diflunisal was found to be equivalent to 50 drops of tilidine N and to be subjectively well-tolerated. In the pain-relieving therapy of tumour patients diflunisal appears to offer a genuine alternative to centrally-acting analgetics.

Topics: Aged; Cyclohexanecarboxylic Acids; Diflunisal; Dose-Response Relationship, Drug; Humans; Male; Neoplasms; Pain; Salicylates; Tilidine

In clinical rheumatology, the hazardousness of mixed preparations containing cortisone is being stressed even more, their use is only recommended in very special cases and only for short periods. Dolo Visano Supp. sine codeino and Dolo Visano Supp. are remedies which are indicated, like other mixed preparations not containing steroids, in cases of painful muscular overstrain and psychomuscular kinesalgia (symptom range of non-articular rheumatism). In our study, they were used in acute and severe pain conditions in intermediate or short-term therapy until complaints improved. Dolo Visano Supp. sine codeino and Dolo Visano Supp. (with codeine) can contribute in limiting the use of the risky preparations containing cortisone, which have hitherto been applied so frequently.

Topics: Aspirin; Codeine; Diphenhydramine; Drug Combinations; Female; Gout; Humans; Male; Meprobamate; Middle Aged; Muscle Rigidity; Nerve Compression Syndromes; Nicotinic Acids; Osteoarthritis; Pain; Plant Extracts; Salicylamides; Salicylates; Spinal Nerve Roots; Suppositories

Topics: Aged; Analgesics; Analgesics, Opioid; Aniline Compounds; Anti-Inflammatory Agents, Non-Steroidal; Drug Combinations; Humans; Pain; Pyrazoles; Salicylates

Topics: Humans; Pain; Risk; Salicylates

Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Indomethacin; ortho-Aminobenzoates; Pain; Propionates; Pyrazoles; Salicylates

Topics: Diflunisal; Drug Interactions; Humans; Pain; Salicylates

A simple method for bipolar electrical stimulation of the tooth pulp for evaluating pain modulating procedures is described. Stimulation selectivity has been studied by means of cortical evoked potentials before and after gum anaesthesia. Results obtained by constant current and constant voltage stimulation have been compared. Constant voltage stimulation has proved to be more stable in time. This technique is able to differentiate the analgesic effect of a single dose of i.v. lysine acetylsalicylate from saline. Threshold sensation was judged as painful by about half of the subjects.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Dental Pulp; Electric Stimulation; Evoked Potentials; Female; Humans; Lysine; Male; Middle Aged; Pain; Salicylates; Toothache

Topics: Analgesics; Humans; Narcotics; Pain; Salicylates; Tolmetin

Topics: Animals; Body Temperature; Cats; Dogs; Horses; Inflammation; Pain; Salicylates; Swine

Topics: Administration, Topical; Anti-Inflammatory Agents; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Pain; Placebos; Rheumatic Diseases; Salicylates; Terpenes

Topics: Acetanilides; Animals; Anti-Inflammatory Agents; Aspirin; Female; Inflammation; Male; Mice; Pain; Rats; Salicylates

Topics: Analgesics; Aniline Compounds; Dextropropoxyphene; Drug Combinations; Drug Interactions; Humans; Pain; Salicylates

An open study was carried out in general practice to assess the analgesic effectiveness, tolerance and side-effects of salsalate when given at a dosage of 3 g per day for 6 weeks. Sixty-six patients who were known long-term analgesic users were treated: they included 16 with active inflammatory disease of rheumatoid type, 20 with degenerative joint disease, and 27 with other musculo-skeletal conditions. Three patients were withdrawn during the study because of gastro-intestinal upset. Assessments, using rating scale scores, were made pre-trial and at 2-weekly intervals of joint pain, other musculo-skeletal pain, and duration of morning stiffness. The results showed that there was marked improvement in joint pain and morning stiffness, particularly in those patients with inflammatory joint disease. Improvement in musculo-skeletal discomfort was less evident. Side-effects were reported on 24 occasions, the most frequent being dyspepsia. Faecal occult blood tests showed that there were 7 patients with probable blood loss during treatment, 4 of them, however, had no other clinical signs or symptoms of gastrointestinal intolerance.

Topics: Bone Diseases; Chronic Disease; Female; Humans; Male; Middle Aged; Muscular Diseases; Occult Blood; Pain; Salicylates

A multicentric follow-up study was conducted in general practice to assess disease characteristics which determine analgesic needs in non-articular rheumatism. Of 127 patients studied, those with chronic conditions such as brachial fibrositis and tennis elbow with a history extending over more than a month tended to require a longer course of treatment than those whose symptoms related to muscles of the trunk and spine. For most patients a one or two week course of Benoral tablets proved adequate in length and efficacy.

Topics: Adult; Chronic Disease; Drug Administration Schedule; Female; Fibromyalgia; Follow-Up Studies; Humans; Male; Middle Aged; Pain; Salicylates

Topics: Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Humans; Pain; Phenols; Salicylates

Thirty-four patients with analgesic nephropathy were followed at intervals of 1 to 3 months with measurements of creatinine clearance and serum concentration of acetylsalicylic acid (ASA) for a total of 105 patient-years. Diagnostic criteria included total consumption of at least 2 kg of phenacetin and 3 kg of ASA, compatible tissue abnormality on biopsy and evidence of papillary necrosis on an intravenous pyelogram. Nephropathy was induced by the same compound analgesic containing ASA, pehnacetin, caffeine and codeine (APC&C) in 30. Phenacetin was removed from this preparation in 1970 and replaced by an approximately equal amount of ASA (ACC). Creatinine clearance remained unchanged or improved in 11 of 15 patients who stopped taking analgesics containing phenacetin or ASA and in 10 of 11 of those who continued to take the ACC preparation. In contrast, renal function deteriorated in seven of eight patients who continued to abuse APC&C analgesics. The results suggest that phenacetin is necessary for the major nephrotoxic effect of this APC&C combination, but that ASA is not absolved of some nephrotoxicity.

Topics: Analgesics; Aspirin; Caffeine; Codeine; Creatinine; Female; Follow-Up Studies; Humans; Kidney; Kidney Diseases; Pain; Phenacetin; Salicylates; Substance-Related Disorders

Topics: Analgesia; Anesthesia, Local; Community Health Services; Humans; Pain; Pain, Postoperative; Salicylates; Substance-Related Disorders; Terminal Care

A reliable and sensitive method was used to compare the analgesic activities of salicylic acid and aspirin (acetylsalicylic acid) and several phenoxy substituted isosteric pairs. Those isosteric compounds studied did not show analgesic activity. The analgesic activity of aspirin was more than twofold greater than that of salicylic acid.

Topics: Analgesics; Animals; Aspirin; Benzoates; Bradykinin; Isomerism; Lethal Dose 50; Male; ortho-Aminobenzoates; Pain; Rats; Salicylates; Sulfhydryl Compounds

Topics: Aminopyrine; Analgesics; Drug Therapy, Combination; Humans; Narcotic Antagonists; Narcotics; Neoplasms; Pain; Palliative Care; Salicylates; Terminal Care; Time Factors

Topics: Administration, Topical; Gels; Humans; Humic Substances; Inflammation; Pain; Salicylates

Topics: Adolescent; Anemia; Arthritis, Juvenile; Body Height; Child; Child, Preschool; Chronic Disease; Drug Therapy, Combination; Elasticity; Female; Fever; Growth; Humans; Male; Pain; Prednisone; Salicylates; Sex Characteristics; Stress, Mechanical

Topics: Analgesics; Antipyrine; Caffeine; Drug Combinations; Humans; Mandelic Acids; Pain; Salicylamides; Salicylates

Topics: Back Pain; Drug Combinations; Evaluation Studies as Topic; Gels; Heparin; Humans; Menthol; Neuralgia; Pain; Salicylates

Topics: Analgesics; Aspirin; Azepines; Carbamazepine; Codeine; Dextropropoxyphene; Humans; Indomethacin; Methadone; Morphine; Narcotics; Pain; Pentazocine; Pyrazoles; Salicylates; Substance-Related Disorders

Topics: Acetanilides; Analgesics; Arthritis, Rheumatoid; Blood Sedimentation; Chronic Disease; Edema; Female; Finger Joint; Fingers; Humans; Male; Middle Aged; Muscle Contraction; Nausea; Pain; Physical Exertion; Salicylates; Suspensions

Topics: Administration, Oral; Analgesics; Animals; Brain; Brain Chemistry; Chemoreceptor Cells; Disulfiram; Dopamine; Dopamine beta-Hydroxylase; Electric Stimulation; Male; Methyltyrosines; Mice; Norepinephrine; Pain; Placebos; Salicylates

Topics: Anti-Inflammatory Agents; Arthritis, Rheumatoid; Cortisone; Humans; Methods; Pain; Phenylbutazone; Salicylates

Topics: Amygdala; Analgesia; Anesthesia, Local; Brain; Hippocampus; Histamine Release; Hypothermia, Induced; Kinins; Pain; Phenothiazines; Procaine; Prostaglandins; Reticular Formation; Salicylates; Serotonin; Tranquilizing Agents

Topics: Adolescent; Bone Neoplasms; Child; Diagnosis, Differential; Female; Femoral Neoplasms; Humans; Male; Osteoma, Osteoid; Pain; Radiography; Salicylates; Tibia

Topics: Animals; Anti-Inflammatory Agents; Benzyl Compounds; Edema; Female; Fever; Flufenamic Acid; Indomethacin; Lethal Dose 50; Male; Mefenamic Acid; Methylamines; Mice; Naphthalenes; Pain; Peptic Ulcer; Phenylbutazone; Pyrazoles; Rats; Salicylates; Terpenes; Uricosuric Agents

Topics: Adult; Analgesics; Barbiturates; Female; Gynecology; Humans; Naphthalenes; Obstetrics; Pain; Parasympatholytics; Phenacetin; Quinolines; Salicylates

Topics: Abdomen; Acute Disease; Appendicitis; Blood Sedimentation; Child; Diagnosis, Differential; Humans; Male; Pain; Recurrence; Rheumatic Fever; Salicylates

Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Benzoates; Heparin; Humans; Inflammation; Joint Diseases; Ointments; Pain; Salicylates; Spinal Diseases

Topics: Adolescent; Alanine Transaminase; Arthritis, Juvenile; Aspartate Aminotransferases; Bilirubin; Child; Child, Preschool; Clinical Enzyme Tests; Diagnosis, Differential; Female; Fever; Hepatomegaly; Humans; Infant; Leukocyte Count; Liver; Liver Function Tests; Lymphatic Diseases; Male; Pain; Pericarditis; Pleurisy; Salicylates; Sex Factors; Splenomegaly; Sulfobromophthalein

Topics: Adolescent; Adult; Aspirin; Choline; Ear Diseases; Female; Humans; Male; Otitis Media; Pain; Salicylates

Topics: Administration, Oral; Aminopyrine; Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Male; Mice; Pain; Phenylbutazone; Pyridines; Rats; Salicylates; Sulfhydryl Compounds; Thiophenes

Topics: Aminopyrine; Amphetamine; Analgesics; Animals; Anti-Inflammatory Agents; Edema; Imipramine; Male; Mice; Morphine; Pain; Papaverine; Phenylbutazone; Pyridines; Rats; Salicylates; Thiophenes

Topics: Choline; Dry Socket; Female; Gingivitis; Humans; Male; Mouth Diseases; Ointments; Pain; Pericoronitis; Salicylates; Stomatitis

Topics: Aminopyrine; Analgesics; Antidepressive Agents; Antipyrine; Aspirin; Codeine; Dibenzazepines; Humans; Imipramine; Levallorphan; Levorphanol; Methadone; Morphine; Pain; Phenacetin; Phenylbutazone; Pyrazoles; Salicylamides; Salicylates; Sulfonic Acids

Topics: Adrenal Cortex Hormones; Bone Resorption; Calcitonin; Calcium; Female; Fluorides; Humans; Malabsorption Syndromes; Middle Aged; Osteitis Deformans; Pain; Pelvis; Phosphates; Radiography; Salicylates; Sodium

Topics: Analgesics; Animals; Brain Chemistry; Electric Stimulation; Electrodes; Male; Mathematics; Methods; Mice; Pain; Salicylates; Tail; Time Factors

Topics: Age Factors; Analgesics; Animals; Anticonvulsants; Aspirin; Body Weight; Electric Stimulation; Electrodes; Hindlimb; Male; Methods; Mice; Pain; Pentazocine; Phenobarbital; Salicylates; Tail; Time Factors; Urea

Topics: Acetylcholine; Age Factors; Analgesics; Animals; Atropine; Barium; Bradykinin; Catheterization; Chlorides; Diphenhydramine; Dogs; Eledoisin; Femoral Artery; Histamine; Mesenteric Arteries; Norepinephrine; Pain; Papaverine; Procaine; Salicylates; Serotonin; Tripelennamine; Vocalization, Animal

Topics: Adolescent; Adult; Anesthesia, General; Female; Humans; Male; Middle Aged; Pain; Postoperative Complications; Salicylates; Thiamine

Topics: Adolescent; Adult; Ascorbic Acid; Dexamethasone; Female; Humans; Joint Diseases; Male; Middle Aged; Pain; Salicylates; Temporomandibular Joint; Thiamine

Topics: Analgesics; Analgesics, Non-Narcotic; Antipyretics; Dentistry; Drug Therapy; Gingivitis; Humans; Inflammation; Mouth Diseases; Pain; Salicylates; Stomatitis

Topics: Arthritis; Arthritis, Rheumatoid; Circadian Rhythm; Drug Therapy; Humans; Inflammation; Joint Diseases; Pain; Rheumatic Diseases; Salicylates; Toxicology

Topics: Acetanilides; Analgesics; Analgesics, Non-Narcotic; Antipyretics; Aspirin; Dextropropoxyphene; Muscle Relaxants, Central; Pain; Pharmacology; Phenacetin; Phenylbutazone; Salicylamides; Salicylates; Toxicology

Topics: Analgesics; Analgesics, Non-Narcotic; Aniline Compounds; Antipyretics; Aspirin; Humans; Morphine; Muscle Relaxants, Central; Narcotics; Pain; Pyrazoles; Salicylates; Tranquilizing Agents

Topics: Amphetamine; Analgesics; Analgesics, Non-Narcotic; Animals; Antipyretics; Aspirin; Azepines; Bradykinin; Cats; Dextropropoxyphene; Dogs; Levorphanol; Meperidine; Morphine; Narcotics; Pain; Phenylbutazone; Physiology; Piperazines; Research; Salicylates; Sensory Receptor Cells; Spleen; Visceral Pain

Topics: Adolescent; Child; Choline; Fever; Humans; Immune System Diseases; Immunization; Infant; Pain; Salicylates; Toxicology; Vaccination

Topics: Acetanilides; Aminopyrine; Analgesics; Analgesics, Non-Narcotic; Antipyretics; Aspirin; Dextropropoxyphene; Narcotics; Opium; Pain; Phenacetin; Salicylates; Toxicology; Tranquilizing Agents

Topics: Aspirin; Drug Tolerance; Humans; Pain; Salicylates

Topics: Analgesics; Humans; Hydroxybenzoates; Infusions, Parenteral; Morpholines; Pain; Salicylates; Veins

Topics: Disease; Humans; Leg; Lower Extremity; Narcotics; Pain; Salicylates

Topics: Humans; Injections, Intradermal; Pain; Procaine; Rheumatic Diseases; Salicylates

Topics: Acids; Arthritis; Cinnamates; Humans; Pain; Rheumatic Diseases; Salicylates; Sodium

Topics: Humans; Pain; Pain Threshold; Salicylates

Topics: Joints; Pain; Salicylates

Topics: Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Codeine; Drug Combinations; Humans; Pain; Pain Threshold; Salicylates

Topics: Analgesics; Anesthesia; Anesthesiology; Aspirin; Pain; Salicylates

Topics: Analgesics; Anesthesia; Aspirin; Leadership; Pain; Salicylates