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Analgesic Agents (analgesic + agent)
Selected AbstractsOpen-Label Exploration of an Intravenous Nalbuphine and Naloxone Mixture as an Analgesic Agent Following Gynecologic SurgeryPAIN MEDICINE, Issue 6 2007Assaf T. Gordon MD ABSTRACT Objective., The purpose of this series was to explore a 12.5:1 fixed-dose ratio of an intravenous nalbuphine and naloxone mixture (NNM) for use in patients following gynecologic surgery. Design and Patients., Open-label, nonrandomized case series. The first series was a dose-ranging investigation for 12 patients following elective total abdominal hysterectomy or myomectomy. In this series, fentanyl was used for intraoperative analgesia, and patients were assigned to a lower NNM (2.5 mg/0.2 mg) or to a higher NNM (5 mg/0.4 mg) dose group. The second series evaluated the fixed dose of 5 mg nalbuphine/0.4 mg naloxone for four patients undergoing ambulatory gynecologic procedures. In the second series, no opioid agents were administered intraoperatively to eliminate the possibility of mu-opioid reversal by naloxone postoperatively. Outcome Measures., Pain control was assessed using a Verbal Pain Scale (0,10). Vital signs, side effects, and adverse events were recorded to determine drug safety. Results., In the first series, there were no adverse events; however, each patient required rescue medication (either morphine or fentanyl). In the second series, two of the four patients reported a reduction in pain following drug administration and did not require any further analgesic agents in the 3-hour postoperative period. One patient had an asymptomatic lowering of heart rate after receiving the drug. Conclusion., Additional research of the unique combination therapy of nalbuphine and naloxone is warranted to further determine its potential clinical efficacy and safety. [source] Design and Synthesis of 2-Phenoxynicotinic Acid Hydrazides as Anti-inflammatory and Analgesic AgentsARCHIV DER PHARMAZIE, Issue 9 2010Alireza Moradi Abstract A series of 2-phenoxynicotinic acid hydrazides were synthesized and evaluated for their analgesic and anti-inflammatory activities. Several compounds having an unsubstituted phenyl/4-pyridyl or C-4 methoxy substituent on the terminal phenyl ring showed moderate to high analgesic or anti-inflammatory activity in comparison to mefenamic acid as the reference drug. The compounds with highest anti-inflammatory activity were subjected to in vitro COX-1/COX-2 inhibition assays and showed moderate to good COX-1 and weak COX-2 inhibition activities. [source] Design and Synthesis of Some New Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones Substituted with Flurbiprofen as Antiinflammatory and Analgesic Agents.CHEMINFORM, Issue 33 2007Emine Dogdas Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Adult Emergency Department Patients with Sickle Cell Pain Crisis: A Learning Collaborative Model to Improve Analgesic ManagementACADEMIC EMERGENCY MEDICINE, Issue 4 2010Paula Tanabe PhD Abstract Objectives:, The objectives were to report the baseline (prior to quality improvement interventions) patient and visit characteristics and analgesic management practices for each site participating in an emergency department (ED) sickle cell learning collaborative. Methods:, A prospective, multisite longitudinal cohort study in the context of a learning-collaborative model was performed in three midwestern EDs. Each site formed a multidisciplinary team charged with improving analgesic management for patients with sickle cell disease (SCD). Each team developed a nurse-initiated analgesic protocol for SCD patients (implemented after a baseline data collection period of 3.5 months at one site and 10 months at the other two sites). All sites prospectively enrolled adults with an acute pain crisis and SCD. All medical records for patients meeting study criteria were reviewed. Demographic, health services, and analgesic management data were abstracted, including ED visit frequency data, ED disposition, arrival and discharge pain score, and name and route of initial analgesic administered. Ten interviews per quarter per site were conducted with patients within 14 days of their ED discharge, and subjects were queried about the highest level of pain acceptable at discharge. The primary outcome variable was the time to initial analgesic administration. Variable data were described as means and standard deviations (SDs) or medians and interquartile ranges (IQR) for nonnormal data. Results:, A total of 155 patients met study criteria (median age = 32 years, IQR = 24,40 years) with a total of 701 ED visits. Eighty-six interviews were conducted. Most patients (71.6%) had between one and three visits to the ED during the study period. However, after removing Site 3 from the analysis because of the short data enrollment period (3.5 months), which influenced the mean number of visits for the entire cohort, 52% of patients had between one and three ED visits over 10 months, 21% had four to nine visits, and 27% had between 10 and 67 visits. Fifty-nine percent of patients were discharged home. The median time to initial analgesic for the cohort was 74 minutes (IQR = 48,135 minutes). Differences between choice of analgesic agent and route selected were evident between sites. For the cohort, 680 initial analgesic doses were given (morphine sulfate, 42%; hydromorphone, 46%; meperidine, 4%; morphine sulfate and ibuprofen or ketorolac, 7%) using the following routes: oral (2%), intravenous (67%), subcutaneous (3%), and intramuscular (28%). Patients reported a significantly lower targeted discharge pain score (mean ± SD = 4.19 ± 1.18) compared to the actual documented discharge pain score within 45 minutes of discharge (mean ± SD = 5.77 ± 2.45; mean difference = 1.58, 95% confidence interval = .723 to 2.44, n = 43). Conclusions:, While half of the patients had one to three ED visits during the study period, many patients had more frequent visits. Delays to receiving an initial analgesic were common, and post-ED interviews reveal that sickle cell pain patients are discharged from the ED with higher pain scores than what they perceive as desirable. ACADEMIC EMERGENCY MEDICINE 2010; 17:399,407 © 2010 by the Society for Academic Emergency Medicine [source] Aspirin, 110 years laterJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009C. PATRONO Summary., Although conceived at the end of the 19th century as a synthetic analgesic agent with improved gastric tolerability vs. naturally occurring salicylates, acetylsalicylic acid (marketed as aspirin in 1899) turned out to be an ideal antiplatelet agent about 90 years later, following the understanding of its mechanism of action, the development of a mechanism-based biomarker for dose-finding studies, and the initiation of a series of appropriately sized, randomized clinical trials to test its efficacy and safety at low doses given once daily. At the turn of its 110th anniversary, aspirin continues to attract heated debates on a number of issues including (i) the optimal dose to maximize efficacy and minimize toxicity; (ii) the possibility that some patients may be ,resistant' to its antiplatelet effects; and (iii) the balance of benefits and risks in primary vs. secondary prevention. [source] Paracetamol use in musculoskeletal pain: an audit of use and patient perceptions of paracetamol as an effective analgesicMUSCULOSKELETAL CARE, Issue 4 2005Emma J Boger RGN BSc(Hons) DipHE Nurse Researcher Abstract Musculoskeletal pain is a complex problem with often very detrimental consequences which affects a high proportion of the general population. Health care professionals, when prescribing for musculoskeletal pain, often overlook simple analgesia. Patient perceptions of analgesia may vary to those of health care professionals, and in part affect the use of simple analgesia for musculoskeletal pain. This paper describes an audit of paracetamol use and patient perceptions of paracetamol as an effective analgesic agent, in 113 patients attending a musculoskeletal pain outpatient clinic in a university teaching hospital. The audit has helped prompt the development of a multi-disciplinary strategy to achieve optimum management. Copyright © 2005 John Wiley & Sons, Ltd. [source] Negative ion ,chip-based' nanospray tandem mass spectrometry for the analysis of flavonoids in glandular trichomes of Lychnophora ericoides Mart. (Asteraceae)RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2008Leonardo Gobbo-Neto This paper reports a method for the analysis of secondary metabolites stored in glandular trichomes, employing negative ion ,chip-based' nanospray tandem mass spectrometry. The analyses of glandular trichomes from Lychnophora ericoides, a plant endemic to the Brazilian ,cerrado' and used in traditional medicine as an anti-inflammatory and analgesic agent, led to the identification of five flavonoids (chrysin, pinocembrin, pinostrobin, pinobanksin and 3- O -acetylpinobanksin) by direct infusion of the extracts of glandular trichomes into the nanospray ionisation source. All the flavonoids have no oxidation at ring B, which resulted in a modification of the fragmentation pathways compared with that of the oxidised 3,4-dihydroflavonoids already described in the literature. The absence of the anti-inflammatory and antioxidant di- C -glucosylflavone vicenin-2, or any other flavonoid glycosides, in the glandular trichomes was also demonstrated. The use of the ,chip-based' nanospray QqTOF apparatus is a new fast and useful tool for the identification of secondary metabolites stored in the glandular trichomes, which can be useful for chemotaxonomic studies based on metabolites from glandular trichomes. Copyright © 2008 John Wiley & Sons, Ltd. [source] Use of remifentanil as a sedative agent in critically ill adult patients: a meta-analysisANAESTHESIA, Issue 12 2009J. A. Tan Summary This meta-analysis examined the benefits of using remifentanil as a sedative agent in critically ill patients. A total of 11 randomised controlled trials, comparing remifentanil with another opioid or hypnotic agent in 1067 critically ill adult patients, were identified from the Cochrane controlled trials register and EMBASE and MEDLINE databases, and subjected to meta-analysis. Remifentanil was associated with a reduction in the time to tracheal extubation after cessation of sedation (weighted-mean-difference ,2.04 h (95% CI ,0.39 to ,3.69 h); p = 0.02). Remifentanil was, however, not associated with a significant reduction in mortality (relative risk 1.01 (95% CI 0.67,1.52); p = 0.96), duration of mechanical ventilation, length of intensive care unit stay, and risk of agitation (relative risk 1.08 (95% CI 0.64,1.82); p = 0.77) when compared to an alternative sedative or analgesic agent. The current evidence does not support the routine use of remifentanil as a sedative agent in critically ill adult patients. [source] Emergency Department Management of Acute Pain Episodes in Sickle Cell DiseaseACADEMIC EMERGENCY MEDICINE, Issue 5 2007Paula Tanabe PhD ObjectivesTo characterize the initial management of patients with sickle cell disease and an acute pain episode, to compare these practices with the American Pain Society Guideline for the Management of Acute and Chronic Pain in Sickle-Cell Disease in the emergency department, and to identify factors associated with a delay in receiving an initial analgesic. MethodsThis was a multicenter retrospective design. Consecutive patients with an emergency department visit in 2004 for an acute pain episode related to sickle cell disease were included. Exclusion criteria included age younger than 18 years. A structured medical record review was used to abstract data, including the following outcome variables: analgesic agent and dose, route, and time to administration of initial analgesic. Additional variables included demographics, triage level, intravenous access, and study site. Mann,Whitney U test or Kruskal,Wallis test and multivariate regression were used to identify differences in time to receiving an initial analgesic between groups. ResultsThere were 612 patient visits, with 159 unique patients. Median time to administration of an initial analgesic was 90 minutes (25th to 75th interquartile range, 54,159 minutes). During 87% of visits, patients received the recommended agent (morphine or hydromorphone); 92% received the recommended dose, and 55% received the drug by the recommended route (intravenously or subcutaneously). Longer times to administration occurred in female patients (mean difference, 21 minutes; 95% confidence interval = 7 to 36 minutes; p = 0.003) and patients assigned triage level 3, 4, or 5 versus 1 or 2 (mean difference, 45 minutes; 95% confidence interval = 29 to 61 minutes; p = 0.00). Patients from study sites 1 and 2 also experienced longer delays. ConclusionsPatients with an acute painful episode related to sickle cell disease experienced significant delays to administration of an initial analgesic. [source] Morphine modulation of temporomandibular joint-responsive units in superficial laminae at the spinomedullary junction in female rats depends on estrogen statusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2008A. Tashiro Abstract The influence of analgesic agents on neurons activated by stimulation of the temporomandibular joint (TMJ) region is not well defined. The spinomedullary junction [trigeminal subnucleus caudalis (Vc)/C1,2] is a major site of termination for TMJ sensory afferents. To determine whether estrogen status influences opioid-induced modulation of TMJ units, the classical opioid analgesic, morphine, was given to ovariectomized (OvX) rats and OvX rats treated for 2 days with low-dose (LE2) or high-dose (HE2) 17,-estradiol-3-benzoate. Under thiopental anesthesia, TMJ units in superficial and deep laminae at the Vc/C1,2 junction were activated by injection of ATP (1 mm) directly into the joint space. In superficial laminae, morphine inhibited evoked activity in units from OvX and LE2 rats in a dose-related and naloxone-reversible manner, whereas units from HE2 rats were not inhibited. By contrast, in deep laminae, morphine reduced TMJ-evoked unit activity similarly in all groups. Morphine reduced the background activity of units in superficial and deep laminae and resting arterial pressure similarly in all groups. Morphine applied to the dorsal surface of the Vc/C1,2 junction inhibited all units independently of E2 treatment. Quantitative polymerase chain reaction and immunoblots revealed a similar level of expression for ,-opioid receptors at the Vc/C1,2 junction in LE2 and HE2 rats. These results indicated that estrogen status differentially affected morphine modulation of TMJ unit activity in superficial, but not deep, laminae at the Vc/C1,2 junction in female rats. The site(s) for estrogen influence on morphine-induced modulation of TMJ unit activity was probably outside the medullary dorsal horn. [source] Epidural Catheter Analgesia in Dogs and Cats: Technique and Review of 182 Cases (1991,1999)JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2001Bernie D. Hansen DVM, DACVECC Abstract Objective: To characterize the indications and techniques for catheterization of the epidural space to treat pain in dogs and cats in a veterinary teaching hospital intensive care unit, and describe the analgesic regimens used in those patients. To provide a detailed description of the technique of epidural catheterization in companion animals. Design: Retrospective case series and clinical practice review. Setting: The Veterinary Teaching Hospital at the North Carolina State University College of Veterinary Medicine. Animals: Records from 160 dogs and 22 cats that had epidural catheters placed were identified. Interventions: Epidural catheterization for the purpose of providing analgesia for a variety of surgical and medical disorders was performed on both awake and anesthetized patients. Measurements and main results: The most frequently used analgesic agents were preservative-free morphine and bupivacaine. 2The range of duration of catheter dwell time was 1.3,332 hours, with a mean duration of 50 hours and a median of 39 hours. Suspicion of catheter malpositioning prompted radiographic imaging of the catheter in 44 patients, and malpositioning was confirmed in 6 of those. Catheter tip positioning was recorded in 46 patients. The tip was located at L3-L6 in 16, and T5-L3 in 30. Twenty-seven of those 30 patients were catheterized to treat pain associated with thoracotomy, forelimb amputation, pancreatitis, or peritonitis. Fifty-one (28%) patients received no analgesics beyond those provided by the epidural catheter. Conclusions: Epidural administration of analgesia appeared to provide significant pain relief and was adequate as a sole analgesic treatment in some patients. Serious complications in these critically ill animals appeared to be uncommon. (J Vet Emerg Crit Care 2001; 11(2): 95,103) [source] Neurophysiological techniques to assess pain in animalsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2006J. C. MURRELL Neurophysiological techniques are widely applied to animals, both in the search as a monitor for adequacy of anaesthesia, and studies to assess the efficacy of analgesic agents. Laboratory animals have been extensively used in models to investigate pain in man. However a substantial number of studies have also used neurophysiological techniques to increase knowledge of pain in specific animal species, with the aim of improving animal welfare. This review provides an overview of neurophysiological techniques involving the brain that have been used in the assessment of pain in animals. An explanation of the methodology of EEG recording, with particular emphasis on veterinary studies, is given. Neurophysiological models developed to assess pain in different species are described, and their relevance to advancements in animal welfare or best clinical practice indicated. [source] ,2 -Agonists as analgesic agentsMEDICINAL RESEARCH REVIEWS, Issue 2 2009Maria Paola Giovannoni Abstract It is well known that norepinephrine is involved in the control of pain by modulating pain-related responses through various pathways. ,2 -Adrenergic agonists have a well-established analgesic profile and, in the recent years, have found a wider application, in particular as adjunct to anesthetics and analgesics in perioperative settings. This review analyzes the ,2 -agonists currently in clinical use, starting from the prototype Clonidine, as well as the most promising and studied molecules. In addition, an overview of the imidazoles, imidazolines, and hydroxyethyl-thioureas derivatives published in both the open and patented literature is presented, providing chemical description and pharmacological data. Finally, the most commonly ,2 -agonists used in veterinary medicine are described. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 2, 339,368, 2009 [source] Nausea and Vomiting Side Effects with Opioid Analgesics during Treatment of Chronic Pain: Mechanisms, Implications, and Management OptionsPAIN MEDICINE, Issue 4 2009Frank Porreca PhD ABSTRACT Objectives., Gastrointestinal (GI) side effects such as nausea and vomiting are common following opioid analgesia and represent a significant cause of patient discomfort and treatment dissatisfaction. This review examines the mechanisms that produce these side effects, their impact on treatment outcomes in chronic pain patients, and counteractive strategies. Results., A number of mechanisms by which opioids produce nausea and vomiting have been identified. These involve both central and peripheral sites including the vomiting center, chemoreceptor trigger zones, cerebral cortex, and the vestibular apparatus of the brain, as well as the GI tract itself. Nausea and vomiting have a negative impact on treatment efficacy and successful patient management because they limit the effective analgesic dosage that can be achieved and are frequently reported as the reason for discontinuation of opioid pain medication or missed doses. While various strategies such as antiemetic agents or opioid switching can be employed to control these side effects, neither option is ideal because they are not always effective and incur additional costs and inconvenience. Opioid-sparing analgesic agents may provide a further alternative to avoid nausea and vomiting due to their reduced reliance on mu-opioid signalling pathways to induce analgesia. Conclusions., Nausea and vomiting side effects limit the analgesic efficiency of current opioid therapies. There is a clear need for the development of improved opioid-based analgesics that mitigate these intolerable effects. [source] Open-Label Exploration of an Intravenous Nalbuphine and Naloxone Mixture as an Analgesic Agent Following Gynecologic SurgeryPAIN MEDICINE, Issue 6 2007Assaf T. Gordon MD ABSTRACT Objective., The purpose of this series was to explore a 12.5:1 fixed-dose ratio of an intravenous nalbuphine and naloxone mixture (NNM) for use in patients following gynecologic surgery. Design and Patients., Open-label, nonrandomized case series. The first series was a dose-ranging investigation for 12 patients following elective total abdominal hysterectomy or myomectomy. In this series, fentanyl was used for intraoperative analgesia, and patients were assigned to a lower NNM (2.5 mg/0.2 mg) or to a higher NNM (5 mg/0.4 mg) dose group. The second series evaluated the fixed dose of 5 mg nalbuphine/0.4 mg naloxone for four patients undergoing ambulatory gynecologic procedures. In the second series, no opioid agents were administered intraoperatively to eliminate the possibility of mu-opioid reversal by naloxone postoperatively. Outcome Measures., Pain control was assessed using a Verbal Pain Scale (0,10). Vital signs, side effects, and adverse events were recorded to determine drug safety. Results., In the first series, there were no adverse events; however, each patient required rescue medication (either morphine or fentanyl). In the second series, two of the four patients reported a reduction in pain following drug administration and did not require any further analgesic agents in the 3-hour postoperative period. One patient had an asymptomatic lowering of heart rate after receiving the drug. Conclusion., Additional research of the unique combination therapy of nalbuphine and naloxone is warranted to further determine its potential clinical efficacy and safety. [source] Current United Kingdom sedation practice in pediatric intensive carePEDIATRIC ANESTHESIA, Issue 7 2007IAN A. JENKINS FRCPE FRCA Summary Background:, The aim of this study was to investigate the current practice of sedation, analgesia, and neuromuscular blockade in critically ill children on pediatric intensive care units (PICUs) in the UK and identify areas that merit further study. Methods:, Data were gathered in a prospective observational study of 338 critically ill children in 20 UK PICUs. Results:, There is considerable variation in clinical practice. A total of 24 different sedative and analgesic agents were used during the study. The most commonly used sedative and analgesic agents were midazolam and morphine. Four different neuromuscular blockers (NMBs) were used, most commonly vecuronium. There were differences in treatment between cardiac and noncardiac children, but there were a greater number of infants and neonates in the cardiac group. NMBs were used in 30% of mechanically ventilated patients. Withdrawal symptoms were reported in 13% of ventilated patients, relatively early in their stay; weaning sedative agents (,tapering') was apparently of no benefit. The use of clonidine in this setting was noted. Physical restraints were used in 7.4%. Propofol was used but in only 2.6% of patients, all over the age of 4 years, and not exceeding 2 mg·kg,1·h,1. No side effects attributable to ,propofol syndrome' were noted. Conclusions:, There is considerable heterogeneity of sedation techniques. NMBs are used in a large portion of this population. Withdrawal symptoms were associated with higher doses of sedation and greater lengths of stay and were not ameliorated by withdrawing sedation gradually (,tapering'). [source] Regional anaesthesia and pain managementANAESTHESIA, Issue 2010I. Power Summary Despite recent advances in analgesia delivery techniques and the availability of new analgesic agents with favourable pharmacokinetic profiles, current evidence suggests that postoperative pain continues to be inadequately managed, with the proportion of patients reporting severe or extreme postoperative pain having changed little over the past decade. Regional techniques are superior to systemic opioid agents with regards to analgesia profile and adverse effects in the context of general, thoracic, gynaecological, orthopaedic and laparoscopic surgery. Outcome studies demonstrate that regional analgesic techniques also reduce multisystem co-morbidity and mortality following major surgery in high risk patients. This review will discuss the efficacy of regional anaesthetic techniques for acute postoperative analgesia, the impact of regional block techniques on physiological outcomes, and the implications of acute peri-operative regional anaesthesia on chronic (persistent) postoperative pain. [source] Synthesis and Pharmacological Evaluation of N -(Dimethylamino)ethyl Derivatives of Benzo- and PyridopyridazinonesARCHIV DER PHARMAZIE, Issue 1 2009Wanda Pakulska Abstract New N -(dimethylamino)ethyl derivatives of phthalazinones and pyridopyridazinones 7, 9 were synthesized and assayed as potential analgesic agents in the hot-plate, tail-flick, and writhing tests. Pharmacological assay demonstrated that eight (in ten) of the newly synthesized compounds showed antinociceptive activity. Especially, 2-[2-(dimethylamino)ethyl]-4-phenyl-2H -phthalazin-1-one 7a showed remarkably higher antinociceptive activity in all tests. This is connected with influence on supraspinal, spinal, and peripheral structures. The decreased sensitivity to the pain stimulus in the hot-plate was higher than that of metamizole. [source] The management of cancer pain,CA: A CANCER JOURNAL FOR CLINICIANS, Issue 2 2000Dr. Nathan I. Cherny MBBS Any therapeutic strategy developed for patients experiencing cancer pain depends on the goals of care, which can be broadly categorized as prolonging survival, optimizing comfort, and optimizing function. The relative priority of these goals for any individual should direct therapeutic decision-making. By combining primary treatments, systemic analgesic agents, and other techniques, most cancer patients can achieve satisfactory relief of pain. In cases where pain appears refractory to these interventions, invasive anesthetic or neurosurgical maneuvers may be necessary, and sedation may be offered to those with unrelieved pain at the end of life. The principles of analgesic therapy are presented, as well as the practical issues involved in drug administration, ranging from calculating dosage to adverse effects, and, when necessary, how to switch and/or combine therapies. Adjuvant analgesics, which are drugs indicated for purposes other than relief of pain but which may have analgesic effects, are also listed and discussed in some detail. Surgical and neurodestructive techniques, such as rhizotomy or cordotomy, although not frequently required or performed, represent yet other options for patients with unremitting pain and diminished hope of relief. Although cancer pain can be a complex medical problem arising from multiple sources, patients should be assured that suffering is not inevitable and that relief is attainable. [source] Cellular Actions Of Opioids And Other Analgesics: Implications For Synergism In Pain ReliefCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2000MacDonald J Christie SUMMARY 1. ,-Opioid receptor agonists mediate their central analgesic effects by actions on neurons within brain regions such as the mid-brain periaqueductal grey (PAG). Within the PAG, ,-opioid receptor-mediated analgesia results from inhibition of GABAergic influences on output projection neurons. We have established that ,-opioid receptor activation in the PAG causes a presynaptic inhibition of GABA release that is mediated by activation of a voltage-dependent K+ channel via 12-lipoxygenase (LOX) metabolites of arachidonic acid. 2. At a cellular level, ,-opioid agonists have also been shown to open inwardly rectifying K+ channels, close voltage-gated Ca2+ channels and presynaptically inhibit glutamatergic synaptic transmission in the PAG. 3. The ,-opioid receptor-mediated presynaptic inhibition of GABAergic transmission was abolished by phospholipase A2 inhibitors and non-specific LOX and specific 12-LOX inhibitors. Cyclo-oxygenase (COX) and specific 5-LOX inhibitors did not reduce the inhibitory effects of ,-opioid agonists. 4. The opioid actions on GABAergic transmission were mimicked by arachidonic acid and 12-LOX metabolites, but not 5-LOX metabolites. The efficacy of ,-opioids was enhanced synergistically by treatment of PAG neurons with inhibitors of the other major enzymes responsible for arachidonic acid metabolism, COX and 5-LOX. 5. These results explain a previously described analgesic action of COX inhibitors in the central nervous system that was both independent of prostanoid release and inhibited by opioid receptor antagonists and they also explain the synergistic interaction of opioids with COX inhibitors. These findings also suggest new avenues for the development of centrally active analgesic agents involving combinations of lowered doses of opioids and specific 5-LOX inhibitors. [source] | |||||||||||||||||||||||||