benzofurans and Pain--Postoperative

Urinary catheterization during surgical interventions causes postoperative catheter-related bladder discomfort (CRBD). Antimuscarinic agents are the mainstay of treatment for overactive bladder (OAB). As the symptoms of CRBD mimic to OAB, so we designed this study to assess the efficacy of solifenacin and darifenacin for prevention of CRBD.. Ninety patients of either sex undergoing elective spine surgery and requiring urinary catheterization were randomly assigned into three groups to receive oral solifenacin 5 mg (Group S), darifenacin 7.5 mg (Group D) and placebo (Group C) 1 hour prior to induction of anesthesia. Anesthesia technique was identical in all the groups. Catheter-related bladder discomfort (CRBD) was evaluated in 4-point scale (1 = no discomfort, 2 = mild discomfort, 3 = moderate discomfort, 4 = severe discomfort), on arrival (0 hour) and at 1, 2, and 6 hours postoperatively. Patients were provided patient-controlled analgesia with fentanyl for postoperative pain relief.. There were no significant differences in demographic profile and fentanyl requirements (P>0.05). The prevalence and severity of CRBD were significantly less in the group D and group S compared with the group C at all time intervals (P<0.05).. Pretreatment with oral solifenacin or darifenacin reduces catheter-related bladder discomfort with no clinically relevant significant side effects.

Topics: Analgesics, Opioid; Benzofurans; Double-Blind Method; Female; Fentanyl; Humans; Intraoperative Period; Male; Pain, Postoperative; Prospective Studies; Pyrrolidines; Solifenacin Succinate; Treatment Outcome; Urinary Bladder; Urinary Catheterization; Urological Agents

Many studies on the efficacy of preemptive analgesia have been processed in different ways. But the value of preemptive analgesia is still controversial. The goal of this study was to compare analgesic effects of a nonsteroidal anti-inflammatory drug (NSAID) for oral surgical pain according to 3 different administration times.. Using a randomized, parallel-group, single-center, and active-controlled test design, this study was conducted with 80 healthy patients undergoing a surgical removal of an impacted mandibular third molar requiring bone removal. The oral NSAID was first administered 1 hour preoperatively, or 1 hour postoperatively, or no scheduled administration pre- or postsurgery. Whenever patients felt at least moderate pain (score > or =5 on a 10-point scale) after surgery, they were instructed to take the same drug. Pain intensities and times to the first and second onsets of postoperative pain from the end of surgery were assessed for 24 hours.. Of the 80 enrolled subjects in this study, 25 patients were assigned to the preemptive group, 26 to the posttreatment group, and 29 to the no-treatment group. The demographic distribution and duration of surgery in the 3 groups were statistically similar. The mean time to first onset of postoperative pain was significantly prolonged in the posttreatment group (277.2 minutes, P < .05) compared to the preemptive group (158.4 minutes) and the no-treatment group (196.5 minutes). The mean time to second onset of postoperative pain was not significantly different among the 3 groups. No significant statistical difference was found among the mean pain intensities at the first and second onsets of postoperative pain in the 3 groups.. In this small selected group of subjects and limited study design, the analgesic effects of NSAID administered preoperatively were no longer effective for postoperative pain. The results in this population imply that scheduled postoperative analgesics before pain development are adequate for postoperative analgesia without preoperative administration.

Topics: Adolescent; Adult; Analysis of Variance; Anti-Inflammatory Agents; Benzofurans; Chi-Square Distribution; Double-Blind Method; Facial Pain; Female; Humans; Male; Mandible; Molar, Third; Pain, Postoperative; Postoperative Care; Preoperative Care; Pyridines; Time Factors; Tooth Extraction; Tooth, Impacted

To study the analgesic efficacy of enadoline, a selective agonist of the kappa-opioid receptor, a double-blind, randomized comparison was made of enadoline versus placebo and a combination of acetaminophen-codeine in patients with pain after surgical extraction of impacted molar teeth. An initial study involving a comparison of enadoline, a combination, and placebo failed to show any analgesic effect of enadoline. Therefore, a second study with the same design but using higher doses of enadoline was conducted. Despite continued safety and tolerability even at the higher doses, enadoline could not be shown to be superior to placebo. The acetaminophen-codeine combination was significantly more effective than enadoline or placebo. Enadoline did not show analgesic efficacy in this study. Possible reasons for this lack of efficacy are discussed.

Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Benzofurans; Codeine; Double-Blind Method; Drug Combinations; Humans; Male; Molar, Third; Pain, Postoperative; Pyrrolidines; Receptors, Opioid, kappa; Tooth Extraction

Enadoline, a selective agonist of the kappa-opioid receptor, was studied for its analgesic efficacy in patients with pain after obstetric or gynecologic surgery. An initial study involving a comparison of enadoline (2, 5, 15 micrograms), an acetaminophen-codeine (ACET/COD) combination, and placebo showed all treatments to be ineffective analgesics. Therefore, a second study with the same design but using higher doses of enadoline (15 and 25 micrograms) and replacing ACET/COD with morphine 10 mg i.m. was conducted. Enadoline 25 micrograms produced similar pain relief to that of morphine, although of shorter duration, and better than enadoline 15 micrograms or placebo. However, enadoline was associated with dose-limiting neuropsychiatric adverse events, which led to early termination of the study.

Topics: Abdomen; Acetaminophen; Adult; Analgesia; Analgesia, Obstetrical; Analgesics, Opioid; Benzofurans; Codeine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Middle Aged; Morphine; Pain, Postoperative; Pelvis; Placebos; Pyrrolidines; Receptors, Opioid, kappa

CR4056 is a novel imidazoline-2 (I2 ) ligand exhibiting potent analgesic activity in animal models of pain. In this study, we investigated the effects of CR4056 in a well-established model of postoperative pain where rats develop hyperalgesia in the injured hind paw.. By measuring paw withdrawal threshold to mechanical pressure, we studied the pharmacology of CR4056, potential sex differences in pain perception and response to treatment, and the pharmacodynamic interaction of CR4056 with morphine.. Oral CR4056 and subcutaneous morphine dose-dependently reversed the hyperalgesic response. Analgesic effects of CR4056 were completely suppressed by the non-selective imidazoline I2 /α2 -adrenoceptor antagonist idazoxan, were partially reduced (~30%; P < 0.05) by the selective α2 -adrenoceptor antagonist yohimbine, but were not influenced by the non-selective I1 /α2 -adrenoceptor antagonist efaroxan or by the μ opioid receptor antagonist naloxone. We found no differences in responses to CR4056 or morphine between male and female rats. However, females had a lower pain threshold than males, and needed lower doses of drugs to reach a significant analgesia. When CR4056 and morphine were combined, their median effective doses were lower than expected for additive effects, both in males and in females. Isobolographic analysis confirmed a synergism between CR4056 and morphine.. CR4056 is a novel pharmacological agent under development for postoperative pain both as stand-alone treatment and in association with morphine. CR4056 has successfully completed Phase I studies for tolerability and pharmacokinetics in healthy volunteers, and is currently entering the first proof-of-concept study in patients.

Topics: Adrenergic alpha-2 Receptor Antagonists; Analgesics; Analgesics, Opioid; Animals; Benzofurans; Binding Sites; Drug Synergism; Female; Hyperalgesia; Idazoxan; Imidazoles; Imidazoline Receptors; Male; Morphine; Naloxone; Narcotic Antagonists; Pain, Postoperative; Quinazolines; Rats, Sprague-Dawley; Yohimbine

Enadoline is a highly selective and potent kappa-opioid receptor agonist. This report describes and compares the activities of enadoline and morphine in a rat model of postoperative pain. A 1 cm incision through the muscle and skin of the plantar surface of the right hind paw induced thermal hyperalgesia as well as static and dynamic allodynia lasting at least 2 days. Postoperative testing was carried out using the plantar test for thermal hyperalgesia, von Frey hairs for static allodynia and light stroking with a cotton bud for dynamic allodynia. A single i.v. dose of enadoline 15 min before surgery dose-dependently (1-100 microg/kg) blocked the development of thermal hyperalgesia as well as static and dynamic allodynia for over 24 h with respective MEDs of < or = 1, 10 and 10 microg/kg. The administration of enadoline (100 microg/kg, i.v.), 1 h after surgery, completely blocked the maintenance of the hyperalgesic and allodynic responses, but its duration of action was much shorter (2 h) than when administered before surgery. Previous studies have shown that administration of morphine (1-6 mg/kg, s.c.) 0.5 h before surgery can prevent the development of thermal hyperalgesia with a MED of < or =1 mg/kg, but it has little effect on static allodynia. In the present study similar administration of morphine (1-3 mg/kg), unlike enadoline, had no effect on the development of dynamic allodynia. Morphine dose-dependently (1-6 mg/kg, s.c.) potentiated isoflurane-induced sleeping time and respiratory depression in the rat. However, whilst enadoline also (1-1000 microg/kg, i.v.) potentiated isoflurane-induced sleeping time, it did not cause respiratory depression. It is suggested that enadoline may possess therapeutic potential as a pre-emptive antihyperalgesic and antiallodynic agent.

Topics: Anesthesia Recovery Period; Animals; Benzofurans; Blood Gas Analysis; Disease Models, Animal; Hot Temperature; Hyperalgesia; Male; Morphine; Pain, Postoperative; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Respiratory Mechanics; Skin; Touch