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Analgesic Effects (analgesic + effects)

Distribution by Scientific Domains

Medical Sciences	90%
Life Sciences	6%

Distribution within Medical Sciences

Anesthesia & Pain Management	33%
Pharmacology & Pharmaceutical Medicine	30%
Pediatrics	6%
7 Other Subdomains	25%

Selected Abstracts

Analgesic Effects of Ethanol Are Influenced by Family History of Alcoholism and Neuroticism

ALCOHOLISM, Issue 8 2010
Elizabeth Ralevski
Background:, Although personality factors and family history of substance abuse influence how individuals experience pain and respond to analgesics, the combined effects of those factors have not been extensively studied. The objective of this study was to consider the possible role of personality trait of neuroticism and family history of alcoholism on the experience of pain and their role in the analgesic response to an ethanol challenge. Methods:, Forty-eight healthy subjects participated in this study; thirty-one had a positive family history of alcoholism (FHP), seventeen had a negative family history of alcoholism (FHN). They were also categorized based on their neuroticism (N) scores (low N = 28, and high N = 20). This was a double-blind, placebo-controlled, randomized, within-subject design study of intravenous administration of three doses of ethanol. The testing consisted of 3 separate test days scheduled at least 3 days apart. Test days included a placebo day (saline solution), low-exposure ethanol day (targeted breathalyzer = 0.040 g/dl), and high-exposure ethanol day (targeted breathalyzer = 0.100 g/dl). Noxious electrical stimulation and pain assessments were performed prior to start of infusion and at the 60-minute infusion mark. Results:, The analgesic effect of ethanol was mediated by an interaction between the personality trait of neuroticism and family history. Individuals with family history of alcoholism and high N scores reported significantly more analgesia on low dose of ethanol than those with low N scores. There was no difference in the analgesic response to ethanol among FHNs with low and high N scores. Conclusion:, These findings support the conclusion that neuroticism and family history of alcoholism both influence the analgesic response of alcohol. Individuals with high N scores and FHP have the strongest response to ethanol analgesia particularly on the low exposure to alcohol. [source]

Comparison of Analgesic Effects of Khat (Catha edulis Forsk) Extract, D-Amphetamine and Ibuprofen in Mice

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2000
JOHN CONNOR
We have compared the analgesic properties of khat (Catha edulis Forsk) extract, amphetamine and ibuprofen in mice. After intragastric administration of the drugs analgesia was measured relative to water-injected controls using the hot-plate, the tail-flick, and abdominal-constriction tests. At the highest doses examined (amphetamine 1.8 mg kg,1, ibuprofen 90 mg kg,1, khat extract 1800 mg kg,1), all three substances produced analgesia, but the order of efficacy varied with the test. Khat and ibuprofen were significantly different from the control in the hot-plate assay at three or more time points post-injection. In the tail-flick test, khat and amphetamine were efficacious; ibuprofen means were somewhat lower but still significantly different from control. Higher doses of the drugs decreased the number of responses in the acetic acid-induced abdominal-constriction assay. We conclude that khat, like amphetamine and ibuprofen, can relieve pain. Differences in assay results may reflect differences in modes and sites of action, as well as in the type of pain generated by the chemical and thermal stimuli for nociception. [source]

Effects of Intrathecal Injection of Nicotine on the Analgesic Effects of Isoflurane in a Model of Inflammatory Pain

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009
Wei Cheng
After having established the mice model of analgesia by intraperitoneally injecting (i.p.) appropriate doses of isoflurane, nicotine, a neuronal nicotinic acetylcholine receptor agonist was intrathecally injected. The effects of isoflurane and nicotine on paw licking times and formalin-induced c-fos expression in the spinal cord dorsal horn were examined. Our correlative studies have shown that isoflurane can decrease the paw licking times and simultaneously suppress c-fos expression after injection of formalin in the mice. Nicotine can partially antagonize the effects induced by isoflurane above. Spinal neuronal nicotinic acetylcholine receptors may be important targets for the analgesic effects of isoflurane in formalin pain. [source]

Analgesic effects of preincisional administration of dextromethorphan and tenoxicam following laparoscopic cholecystectomy

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2004
C-C. Yeh
Background:, Pre-incisional treatment with either N -methyl-D-aspartate (NMDA) receptor antagonists or non-steroidal anti-inflammatory drugs (NSAIDs) improves postoperative pain relief. This study examines the effect on postlaparoscopic cholecystectomy (LC) pain of a combination of dextromethorphan (DM), a NMDA-receptor antagonist, and tenoxicam, a NSAID, given preoperatively. Methods:, Eighty-eight ASA I or II patients scheduled for LC were entered into a randomized, double-blind study and randomly allocated to one of four groups. Controls received 20 mg (4 ml) of chlorpheniramine maleate (CPM) IM and 4 ml of normal saline (N/S) IV. Group DM received 40 mg of DM (containing 20 mg of CPM) IM and 4 ml of N/S IV. Group T were given CPM 20 mg IM, and tenoxicam 40 mg (4 ml) IV. Group DM + T were given DM 40 mg (containing 20 mg of CPM) IM, and tenoxicam 40 mg IV. All treatments were given 30 min before skin incision. Analgesic effects were evaluated by Visual Analog Scale (VAS) pain scores at rest and during coughing, at 1, 2, 4, 12, 24 and 48 h after surgery. The time to the first request for meperidine for pain relief, and total meperidine consumption, were recorded for 48 h after surgery. Results:, Compared to controls, patients given DM and DM + T first requested meperidine significantly later, had lower meperidine consumption, made fewer requests for meperidine, and had lower pain scores. There were significant differences between the DM + T and T groups at 2 and 4 h in both resting and incident VAS pain scores, the incidence of meperidine requests and the time to first meperidine injection. There were significant differences between groups DM and T at 1 h for resting pain and at 2 and 4 h for incident pain. Except for a significant difference in the incident pain score 1 h after surgery, there were no other differences in pain scores between the DM and DM + T groups. Neither synergistic nor antagonistic interaction was observed between DM and tenoxicam. Conclusions:, The results suggest that pretreatment with DM, but not tenoxicam, provides significant pre-emptive analgesia for postoperative pain management in patients after LC surgery. Combining DM and tenoxicam also gives good pain relief. [source]

Grapefruit Juice Enhances the Exposure to Oral Oxycodone

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2010
Tuija H. Nieminen
The objective of this study was to examine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral oxycodone in a randomized cross-over study with two phases at an interval of 4 weeks. Twelve healthy volunteers ingested 200 ml of grapefruit juice or water t.i.d. for 5 days. An oral dose of oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed from the plasma samples for 48 hr and behavioural and analgesic effects were recorded for 12 hr. Grapefruit juice increased the mean area under the oxycodone concentration,time curve (AUC0,,) by 1.7-fold (p < 0.001), the peak plasma concentration by 1.5-fold (p < 0.001) and the half-life of oxycodone by 1.2-fold (p < 0.001) as compared to the water. The metabolite-to-parent AUC0,, ratios (AUCm/AUCp) of noroxycodone and noroxymorphone decreased by 44% (p < 0.001) and 45% (p < 0.001), respectively. Oxymorphone AUC0,, increased by 1.6-fold (p < 0.01) after grapefruit juice, but the AUCm/AUCp remained unchanged. Pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice. Analgesic effects were not influenced. Grapefruit juice inhibited the CYP3A4-mediated first-pass metabolism of oxycodone, decreased the formation of noroxycodone and noroxymorphone and increased that of oxymorphone. We conclude that dietary consumption of grapefruit products may increase the concentrations and effects of oxycodone in clinical use. [source]

Lumbosacral spinal cord somatosensory evoked potentials for quantification of nociception in horses

EQUINE VETERINARY JOURNAL, Issue 3 2010
J. P. A. M. Van LOON
Summary Reasons for performing study: There is a need for objective evaluation and quantification of the efficacy of analgesic drugs and analgesic techniques in horses. Objectives: To determine whether lumbosacral spinal cord somatosensory evoked potentials (SSEP) can be a useful and reliable tool to assess nociception in equines. Methods: SSEPs and electromyograms (EMG) from the epaxial muscles were recorded simultaneously, following electrical stimulation applied to the distal hindlimb in lightly anaesthetised Shetland ponies (n = 7). In order to validate the model, the effect of increasing stimulus intensity was documented and the conduction velocities (CV) of the stimulated nerves were calculated. The effect of epidurally applied methadone (0.4 mg/kg bwt) in a randomised, crossover design was investigated. Results: Two distinct complexes (N1P1 and N2P2) were identified in the SSEP waveform. Based on their latency and conduction velocity and the depressant effect of epidurally applied methadone, the SSEP N2P2 was ascribed to nociceptive A,-afferent stimulation. The SSEP N1P1 originated from non-nociceptive A,-afferent stimulation and was not influenced by epidurally applied methadone. Conclusions and potential relevance: The nociceptive A, component of the SSEP, the N2P2 complex, is presented as a valid and quantitative parameter of spinal nociceptive processing in the horse. Validation of the equine SSEP model enables the analgesic effects of new analgesics/analgesic techniques to be quantified and analgesia protocols for caudal epidural analgesia in equidae improved. [source]

A QSAR analysis of toxicity of Aconitum alkaloids

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2004
Angélica M. Bello-Ramírez
Abstract Biological activity of Aconitum alkaloids may be related to their toxicity rather than to a specific pharmacological action. A Quantitative structure-activity relationships (QSAR) analysis was performed on the following two groups of alkaloids: compounds with an aroyl/aroyloxy group at R14 position (yunaconitine, bulleyaconitine, aconitine, beiwutine, nagarine, 3-acetyl aconitine, and penduline), and compounds with the aroyloxy group at R4 position (N -deacetyllappaconitine, lappaconitine, ranaconitine, N -deacetylfinaconitine, N -deacetylranaconitine). The LD50 (,mol/kg) of the 12 alkaloids were obtained from the literature. LD50 was significantly lower in group 1 than in group 2. The steric and core,core repulsion energies were significantly higher in group 1. The total energy and heat of formation and electronic energies were significantly lower in group 1. The reactivity index of N, C1,, C4, and C6, were similar between groups. The reactivity index of C2, was significantly higher and the reactivity index of C3, and C5, were significantly lower in group 1. Log P and pKa were similar between groups. Molecular weight was significantly higher in group 1. A significant linear relationship was observed between log LD50 and either analgesic log ED50 or local anesthetic log ED50. The LD50/analgesic ED50 obtained from average values was 5.9 for group 1 and 5.0 for group 2. However, the LD50/local anesthetic ED50 was 40.4 and 318, respectively. The study supports that the analgesic effects of these alkaloids are secondary to their toxic effects whereas alkaloids from group 2 are susceptible to be further studied as local anesthetic agents. [source]

Effect of ipriflavone on pain due to recent osteoporotic vertebral crush fracture

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 1 2002
Mohammad M. Rahman
Abstract Aim:,Ipriflavone conserves bone mass in postmenopausal osteoporosis. Salmon calcitonin and alendronate, two other anti-resorptive drugs, have been found to have analgesic effects in osteoporotic acute vertebral fracture. This study aimed to determine if ipriflavone also possesses such an effect. Methods:,Thirty-two women with recent osteoporotic vertebral fractures were randomly assigned to ipriflavone treatment or placebo groups. Ipriflavone was given at the dose of 200 mg three times a day. Non-steroidal anti-inflammatory drugs were given ad libitum in both groups. Calcium carbonate (1 g daily) was administered to all subjects. Intensity of pain at rest, on movement and on pressure, pain rating on a 10-point visual analogue scale, degree of mobility impairment, and supplementary analgesic were assessed at the end of a 3-month period in both groups to assess the analgesic effect of ipriflavone. Results:,Fourteen subjects in the ipriflavone group and 12 in the placebo group completed the trial. After 3 months, all pain variables had decreased significantly in both groups. Intensity of pain at rest and on pressure and supplementary analgesic use were significantly lower in the ipriflavone group compared to the placebo group. Conclusion:,The study shows that ipriflavone has an analgesic adjuvant effect in acute osteoporotic vertebral fracture. [source]

Nitric oxide and pain: ,Something old, something new'

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2009
A. MICLESCU
Challenges have emerged following the revival of nitric oxide (NO) from ,something old', a simple gas derived from nitrogen and oxygen with a role in the early stages of evolution, into ,something new', an endogenously formed biological mediator regulating a wide variety of physiological functions. Although pain is a common sensation, it encompasses multiple neurobiologic components, of which NO is only one. In pain research, the study of NO is complicated by convoluted problems related mostly to the effects of NO, which are pro- or anti-nociceptive depending on the circumstances. This dual function reflects the multi-faceted roles of the NO molecule described in physiology. This review covers current information about NO and its implications in pain mechanisms. In addition, it follows the pain pathways, demonstrating the role of NO in peripheral nociceptive transmission as well in central sensitization. This knowledge may provide the scientific basis for developing new drugs that are indicated for different types of pain, drugs that may be related to the chemical links of NO. A comprehensive approach to understanding the effects of NO will help clinicians identify novel agents that combine the pharmacological profile of native drugs with a controllable manner of NO release. Inhibitors of NO synthesis may have analgesic effects and would be of interest for treating inflammatory and neuropathic pain. Unfortunately, only a few of these compounds have reached the stage of clinical pain trials. [source]

Reactive oxygen species in rats with chronic post-ischemia pain

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2009
K. H. KWAK
Background: An emerging theme in the study of the pathophysiology of persistent pain is the role of reactive oxygen species (ROS). In the present study, we examined the hypothesis that the exogenous supply of antioxidant drugs during peri-reperfusion would attenuate pain induced by ischemia/reperfusion (IR) injury. We investigated the analgesic effects of three antioxidants administered during peri-reperfusion using an animal model of complex regional pain syndrome-type I consisting of chronic post-ischemia pain (CPIP) of the hind paw. Methods: Application of a tight-fitting tourniquet for a period of 3 h produced CPIP in male Sprague,Dawley rats. Low-dose allopurinol (4 mg/kg), high-dose allopurinol (40 mg/kg), superoxide dismutase (SOD, 4000 U/kg), N -nitro- l -arginine methyl ester (l -NAME, 10 mg/kg), or SOD (4000 U/kg)+l -NAME (10 mg/kg) was administered intraperitoneally just after tourniquet application and at 1 and 2 days after reperfusion for 3 days. The effects of antioxidants in rats were investigated using mechanical and cold stimuli. Each group consisted of seven rats. Results: Allopurinol caused significant alleviation in mechanical and cold allodynia for a period of 4 weeks in rats with CPIP. Both SOD and l -NAME, which were used to investigate the roles of superoxide (O2 ,,) and nitric oxide (NO) in pain, also attenuated neuropathic-like pain symptoms in rats for 4 weeks. Conclusions: Our findings suggest that O2 ,, and NO mediate IR injury-induced chronic pain, and that ROS scavengers administered during the peri-reperfusion period have long-term analgesic effects. [source]

Biomimetic affinity purification of cardiotoxin and its pharmacological effects on the nervous system,

JOURNAL OF MOLECULAR RECOGNITION, Issue 3 2008
Dexian Dong
Abstract Cobra venom is a very precious natural resource. The traditional method for purification of cardiotoxin from cobra venom is a multi-step, high cost, and low recovery procedure. By molecular modeling and docking with SYBYL software, we designed and synthesized an affinity ligand, m-aminobenzoic acid, for high efficiency purification of this therapeutically useful Chinese cobra venom cardiotoxin. The one-step recovery of cardiotoxin reached 64% and the purity reached 92% upon purification. The binding capacity of this synthetic ligand was 9.1,mg cardiotoxin/g moist weight gel and the affinity constant for cardiotoxin was 5.5,×,103,M,1. Unlike a natural affinity ligand, this synthetic ligand is highly stable, and has great potential for industrial scale production of cardiotoxin. In addition, we examined the effects of cardiotoxin on the nervous system in a mouse model. Results showed that cardiotoxin could maintain analgesic effects for 120,min with a dose of less than 0.06,mg/kg (2.8% of the LD50). Administration of 0.12,mg/kg cardiotoxin could improve scopolamine impairments of memory in mice. These results suggest that cardiotoxin may be a potential drug for nervous system diseases. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Hypoalgesia in mice lacking GABA transporter subtype 1

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2008
Yin Fang Xu
Abstract ,-Aminobutyric acid (GABA) transporters play a key role in the regulation of GABA neurotransmission. We reported previously that overexpression of the GABA transporter subtype 1 (GAT1), the major form of the GABA transporter in the CNS, led to hyperalgesia in mice. In the present study, nociceptive responses of GAT1-knockout mice (GAT1,/,) were compared with those of heterozygous (GAT+/,) and wild-type (GAT+/+) mice by four conventional pain models (tail-immersion test, hot-plate test, acetic acid,induced abdominal constriction test, and formalin test). In addition, the analgesic effects of two GAT1-selective inhibitors, NO-711 and tiagabine, were examined in all three genotypes using the same four models. Our data demonstrated that GAT1 deficiency because of genetic knockout or acute blockade by selective inhibitors leads to hypoalgesia in mice. These results confirmed the crucial role of GAT1 in the regulation of nociceptive threshold and suggested that GAT1 inhibitors have the potential for clinical use in pain therapy. © 2007 Wiley-Liss, Inc. [source]

Anti-inflammatory, analgesic and anti-oedematous effects of Lafoensia pacari extract and ellagic acid

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2006
Alexandre P. Rogerio
Lafoensia pacari St. Hil. (Lythraceae) is used in traditional medicine to treat inflammation. Previously, we demonstrated the anti-inflammatory effect that the ethanolic extract of L. pacari has in Toxocara canis infection (a model of systemic eosinophilia). In this study, we tested the antiinflammatory activity of the same L. pacari extract in mice injected intraperitoneally with ,-glucan present in fraction 1 (F1) of the Histoplasma capsulatum cell wall (a model of acute eosinophilic inflammation). We also determined the anti-oedematous, analgesic and anti-pyretic effects of L. pacari extract in carrageenan-induced paw oedema, acetic acid writhing and LPS-induced fever, respectively. L. pacari extract significantly inhibited leucocyte recruitment into the peritoneal cavity induced by ,-glucan. In addition, the L. pacari extract presented significant analgesic, anti-oedematous and anti-pyretic effects. Bioassay-guided fractionation of the L. pacari extract in the F1 model led us to identify ellagic acid. As did the extract, ellagic acid presented anti-inflammatory, anti-oedematous and analgesic effects. However, ellagic acid had no anti-pyretic effect, suggesting that other compounds present in the plant stem are responsible for this effect. Nevertheless, our results demonstrate potential therapeutic effects of L. pacari extract and ellagic acid, providing new prospects for the development of drugs to treat pain, oedema and inflammation. [source]

Melatonin enhances the rewarding properties of morphine: involvement of the nitric oxidergic pathway

JOURNAL OF PINEAL RESEARCH, Issue 4 2007
Noushin Yahyavi-Firouz-Abadi
Abstract:, Melatonin has different interactions with opioids including the enhancement of the analgesic effects of morphine and also reversal of tolerance and dependence to morphine. The present study assessed the effect of melatonin on morphine reward in mice using a conditioned place preference (CPP) paradigm. Our data showed that subcutaneous administration of morphine (1,7.5 mg/kg) significantly increased the time spent in the drug-paired compartment in a dose-dependent manner. Intraperitoneal (i.p.) administration of melatonin (1,40 mg/kg) alone did not induce either CPP or conditioned place aversion (CPA), while the combination of melatonin (5,20 mg/kg) and sub-effective dose of morphine (0.5 mg/kg) led to rewarding effect. We further investigated the involvement of the nitric oxidergic pathway in the enhancing effect of melatonin on morphine CPP, by a general nitric oxide synthase inhibitor, NG -nitro- l -arginine methyl ester (l -NAME). l -NAME (1 and 5 mg/kg, i.p.) alone or in combination with morphine (0.5 mg/kg) did not show any significant CPP or CPA. Co-administration of l -NAME (5 mg/kg) with an ineffective combination of melatonin (1 mg/kg) plus morphine (0.5 mg/kg) produced significant CPP that may imply the similarity of action of melatonin and l -NAME and involvement of the nitric oxidergic pathway in this regard. Our results indicate that pretreatment of animals with melatonin enhances the rewarding properties of morphine via a mechanism which may involve the nitric oxidergic pathway. [source]

Correlation between serum concentrations following continuous intravenous infusion of dexmedetomidine or medetomidine in cats and their sedative and analgesic effects

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2000
Ansah
Dexmedetomidine (DEX) may have some therapeutic advantages over the racemate medetomidine (MED). Here we have examined how serum concentrations of DEX correlate with some of its anaesthetic effects. Cats (n = 6) were administered with a continuous stepwise intravenous (i.v.) infusion of DEX or MED on different occasions in a cross-over design. Maintenance infusion rates (mg/kg/min) used were: DEX = 0.25 (MED = 0.50); DEX = 1 (MED = 2) and DEX = 4 (MED = 8) for infusion steps 1, 2 and 3, respectively. Each maintenance infusion lasted at least 50 min and was preceded with a loading dose. There was no significant difference between serum DEX and 0.5 serum MED concentrations at any dose level nor was there a significant difference between serum DEX and the (entire) serum MED concentrations. There was no significant difference between DEX and MED for sedation, analgesia, muscular relaxation and heart and respiratory rates. For both DEX and MED, serum drug concentration and analgesia were dose-dependent and sedation increased until the end of infusion step 2 (dose level 2) and decreased at the end of step 3 (dose level 3). Muscular relaxation was not dose-dependent. We conclude that increasing the blood concentration of DEX or MED beyond a certain level decreases the level of sedation instead of increasing it even though analgesia increases. The rate at which DEX and MED are metabolized in cats may not be the same. [source]

Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: A randomized, double-blind trial

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2004
G. Dierking
Background: Preliminary clinical studies have suggested that gabapentin may produce analgesia and reduce the need for opioids in postoperative patients. The aim of the present study was to investigate the opioid-sparing and analgesic effects of gabapentin administered during the first 24 h after abdominal hysterectomy. Methods: In a randomized, double-blind study, 80 patients received oral gabapentin 1200 mg or placebo 1 h before surgery, followed by oral gabapentin 600 mg or placebo 8, 16 and 24 h after the initial dose. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 24 h postoperatively. Pain was assessed on a visual analogue scale (VAS) at rest and during mobilization, nausea, somnolence and dizziness on a four-point verbal scale, and vomiting as present/not present at 2, 4, 22 and 24 h postoperatively. Results: Thirty-nine patients in the gabapentin group, and 32 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from median 63 (interquartile range 53,88) mg to 43 (28,60) mg (P < 0.001). We observed a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0 to 2 h, and from 0 to 4 h postoperatively (R2 = 0.30, P = 0.003 and R2 = 0.24 P = 0.008, respectively). No significant differences in pain at rest or during mobilization, or in side-effects, were observed between groups. Conclusion: Gabapentin in a total dose of 3000 mg, administered before and during the first 24 h after abdominal hysterectomy, reduced morphine consumption with 32%, without significant effects on pain scores. No significant differences in side-effects were observed between study-groups. [source]

The cannabinoid CB2 receptor: a good friend in the gut

NEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2007
A. A. Izzo
Abstract, Mammalian tissues express the cannabinoid 1 (CB1) receptor and the cannabinoid 2 (CB2) receptor, the latter being involved in inflammation and pain. In somatic nerve pathways, the analgesic effects of CB2 agonism are well documented. Two papers published in the Journal have provided evidence that CB2 receptor activation inhibits visceral afferent nerve activity in rodents. These exciting findings are discussed in the context of recent data highlighting the emerging role of CB2 receptor as a critical target able to counteract hypermotility in pathophysiological states, gut inflammation and possibly colon cancer. [source]

Effects of ketamine on formalin-induced activity in the spinal dorsal horn of spinal cord-transected cats: differences in response to intravenous ketamine administered before and after formalin

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2000
H. Nagasaka
Background: Although formalin has been widely used as an algesic substance in rodent studies, the unique biphasic effect seen in rats is not present in humans. Humans, like cats, have a monophasic behavioral response to formalin injection. Electrophysiologically, spinal dorsal horn neurons in cats also have what could be considered a monophasic response after the initial burst of activity following formalin injection. Although several studies of the effects of ketamine on formalin responses have been carried out in rodents, we are unaware of similar studies in cats. We hypothesize that such species differences may explain observed differences in preemptive analgesic effects. Therefore, we examined the effects of ketamine on activity of spinal wide dynamic range (WDR) neurons evoked by formalin injection in cats. Methods: We investigated in cats the effect of ketamine on the activity of WDR neurons in the spinal dorsal horn that was evoked by formalin. In addition, we studied the effects of pre- and post-administration of ketamine on the maintained phase of the formalin response. Each dose was a subanesthetic, anesthetic or high anesthetic dose (3.0 mg · kg,1, 10 mg · kg,1, and 30 mg · kg,1). Results: Intravenously administered ketamine produced a dose-dependent depression of evoked activity that was significantly greater when the drug was administered before formalin. Conclusions: In spite of the species differences in responses to formalin, there still appears to be a clear preemptive effect of ketamine in the cat. Species differences may not explain apparent differences between human and animal preemptive analgesia. [source]

Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery

PEDIATRIC ANESTHESIA, Issue 7 2008
SANDRA A. PRINS MD PhD
Summary Background:, The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. Methods:, During surgery all infants (6 months,2 years) received a rectal loading dose of 40 mg·kg,1 paracetamol 2 h before anticipated extubation. On admittance to the pediatric surgical ICU, the children were randomized to receive either a 15 min intravenous infusion of 40 mg·kg,1 propacetamol, a prodrug of paracetamol, or 20 mg·kg,1 paracetamol rectally every 6 h. A population pharmacokinetic analysis of the paracetamol plasma concentration time-profiles was undertaken using nonlinear mixed effects models. The visual analogue scale (VAS) (score 0,10 cm) and COMFORT Behavior scale (score 6,30) were used to monitor analgesia in the 24-h period following surgery. Results:, Twelve infants received intravenous propacetamol and 14 paracetamol suppositories. Paracetamol pharmacokinetics were described according to a two-compartmental model with linear disposition. Pharmacokinetic parameters were standardized to a 70 kg person using allometric ,1/4 power' models. Parameter estimates were: absorption half-life from the rectum 4.6 h, propacetamol hydrolysis half-life 0.028 h, clearance 12 l·h,1·70 kg,1, intercompartmental clearance 116 l·h,1·70 kg,1, central and peripheral volume of distribution 7.9 and 44 l·70 kg,1, respectively. During the 24-h study period 22 infants exhibited VAS scores <4 cm, which was considered a cutoff point. On single occasions four patients, two in each group, exhibited a VAS score ,4 cm. Nine patients in the rectal treatment group and three patients in the intravenous treatment group received midazolam for COMFORT-B scores exceeding 17 (P < 0.05). Conclusions:, Intravenous propacetamol proved to be more effective than rectal paracetamol in infants after craniofacial surgery. Midazolam was more frequently administered to patients receiving paracetamol suppositories, indicating that these children experienced more distress, possibly caused by pain. [source]

Sequential clot strength analyses following diclofenac in pediatric adenotonsillectomy

PEDIATRIC ANESTHESIA, Issue 11 2007
MAIREAD HEANEY FCARCSI FJFICM
Summary Background:, Tonsillectomy is a common pediatric surgical procedure resulting in significant postoperative pain. There is ongoing controversy as to the most satisfactory analgesic regimen. Nonsteroidal antiinflammatory drugs (NSAIDs) are an alternative to opioids in this setting. NSAID use in tonsillectomy has been shown to be opioid sparing in the recovery period and to have similar analgesic effects to opioids in pediatric patients. Because of their nonspecific action on the enzyme cyclo-oxygenase there is potential for increased bleeding which has led many practitioners to avoid NSAIDs completely in this patient population potentially resulting in suboptimal pain control. Our aim in this study was to assess the effect of preoperatively administered diclofenac on the blood clot strength in children undergoing (adeno-) tonsillectomy. Methods:, Twenty patients undergoing (adeno-) tonsillectomy were recruited into this prospective observational study. All patients received 2 mg·kg,1 of diclofenac rectally immediately preoperatively. Blood was taken for thromboelastograph analysis pre-diclofenac and 1 and 4 h post-diclofenac administration. Results:, There was a statistically significant increase in maximal clot strength (MA) at 1 and 4 h after diclofenac. Similarly there was a statistically significant reduction in time to initial fibrin formation (R time) post-diclofenac. There was no primary or secondary hemorrhage. Conclusions:, Diclofenac when given preoperatively does not adversely affect clot strength in the immediate postoperative period when the risk of primary hemorrhage is greatest. [source]

Comparison of two doses of breast milk and sucrose during neonatal heel prick

PEDIATRICS INTERNATIONAL, Issue 2 2010
Tutku Ozdogan
Abstract Background:, The aim of the present study was to test analgesic effects of double- versus single-dose breast milk and compare this effect with efficacy of double- versus single-dose sucrose in a group of healthy term newborns during heel prick blood sampling. Methods:, Healthy newborns (n= 142) were consecutively allocated to one of the six groups: group 1, single-dose breast milk; group 2, single-dose sterile water; group 3, single-dose 12.5% sucrose; group 4, two doses breast milk; group 5, two doses sterile water; and group 6, two doses 12.5% sucrose before the heel prick. The medians for crying time and the pain scores according to the neonatal facial coding system were recorded. Results:, Crying times were 117 s, 126 s, 82 s, 128 s, 117 s, and 95 s in groups 1,6, respectively (P= 0.053). The mean pain scores were 4.60, 5.82, 3.91, 4.94, 5, and 4.05 in groups 1,6, respectively (P= 0.068). There was a significant difference between the groups for mean pain scores at 1 min and 3 min. There was a significant difference between the single-dose sucrose group and single-dose sterile water group at 1 min (P= 0.002). The babies in the sucrose group were active awake, whereas the ones in the breast milk group were asleep before heel prick. Conclusion:, Two doses of sucrose solution were not superior to single-dose sucrose. Neither single nor double doses of breast milk were effective in relieving pain in neonates. Two milliliters breast milk does not reduce response to pain during minor painful procedures in term neonates even when two doses have been given. Further studies are needed. [source]

Collagen-induced arthritis as a model of hyperalgesia: Functional and cellular analysis of the analgesic actions of tumor necrosis factor blockade

ARTHRITIS & RHEUMATISM, Issue 12 2007
Julia J. Inglis
Objective There is a disparity in the animal models used to study pain in rheumatoid arthritis (RA), which tends to be acute in nature, and models used to assess the pathogenesis of RA. The latter models, like human RA, are lymphocyte-driven and polyarthritic. We assessed pain behavior and mechanisms in collagen-induced arthritis (CIA), the model of preclinical arthritis used most commonly in the field of immunology. We then validated the model using anti,tumor necrosis factor (anti-TNF) therapy, which has analgesic effects in models of inflammation as well as in human RA. Methods CIA was induced in DBA/1 mice by immunization with type II collagen at the base of the tail. Swelling and mechanical and thermal hyperalgesia were assessed before and for 28 days after the onset of arthritis. Spontaneous behavior was assessed using an automated activity monitor. Glial activity was assessed by glial fibrillary acidic protein expression, and nerve damage was evaluated by activating transcription factor 3 expression. The actions of anti-TNF therapy on nociception were then evaluated. Results Arthritis resulted in a decrease in the threshold for thermal and mechanical stimuli, beginning on the day of onset. Decreased spontaneous activity was also observed. A significant increase in the number of hyperplasic spinal cord astrocytes was observed beginning 10 days after the onset of arthritis. Anti-TNF therapy was profoundly analgesic, with an efficacy similar to that of cyclooxygenase 2 inhibition, and reduced astrocyte activity in CIA. Conclusion This study shows that the CIA model is suitable for testing not only antiinflammatory but also analgesic drugs for potential use in RA, and highlights the importance of using appropriate disease models to assess relevant pain pathways. [source]

Inhibition of cAMP-dependent protein kinase A: a novel cyclo-oxygenase-independent effect of non-steroidal anti-inflammatory drugs in adipocytes

AUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2 2007
M. Zentella de Piña
Summary 1 Non-steroidal anti-inflammatory drugs (NSAIDs) [acetylsalicylic acid (ASS), naproxen, nimesulide and piroxicam] decreased adrenaline- or dibutyryl cAMP-stimulated glycerol release in isolated adipocytes. We aimed to determine the mechanism of this NSAIDs action. 2 Non-steroidal anti-inflammatory drugs decreased cAMP-dependent protein kinase A (PKA) activity in rat adipocyte lysates and in a commercial bovine heart PKA holoenzyme. If added before cAMP, NSAIDs impaired PKA activation by the cyclic nucleotide; however, if PKA was first activated by cAMP, NSAIDs were ineffective. NSAIDs were also ineffective against PKA catalytic subunits. 3 Consequently, NSAIDs lowered hormone-sensitive lipase translocation from cytosol to lipid storage droplets in adipocytes lysates, the critical event to promote lipolysis. 4 These results indicate that inhibition of PKA activation explains NSAIDs-induced decrease in adrenaline-stimulated lipolysis. We suggest that reproduction of such inhibition in nociceptive cells might enhance the understanding of the mechanism underlying the analgesic effects of NSAIDs. [source]

Grapefruit Juice Enhances the Exposure to Oral Oxycodone

Effects of Intrathecal Injection of Nicotine on the Analgesic Effects of Isoflurane in a Model of Inflammatory Pain

Pharmacokinetic,pharmacodynamic modelling of the analgesic effects of lumiracoxib, a selective inhibitor of cyclooxygenase-2, in rats

BRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010
DA Vásquez-Bahena
Background and purpose:, This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats. Experimental approach:, Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg·kg,1 of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg·kg,1 oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI. Results:, A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT=LT0/(1 +MED). LT0 is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 µg·mL,1. Conclusions:, The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics. [source]

Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2008
C-L Chin
Background and purpose: Activation of cannabinoid CB1 and/or CB2 receptors mediates analgesic effects across a broad spectrum of preclinical pain models. Selective activation of CB2 receptors may produce analgesia without the undesirable psychotropic side effects associated with modulation of CB1 receptors. To address selectivity in vivo, we describe non-invasive, non-ionizing, functional data that distinguish CB1 from CB2 receptor neural activity using pharmacological MRI (phMRI) in awake rats. Experimental approach: Using a high field (7 T) MRI scanner, we examined and quantified the effects of non-selective CB1/CB2 (A-834735) and selective CB2 (AM1241) agonists on neural activity in awake rats. Pharmacological specificity was determined using selective CB1 (rimonabant) or CB2 (AM630) antagonists. Behavioural studies, plasma and brain exposures were used as benchmarks for activity in vivo. Key results: The non-selective CB1/CB2 agonist produced a dose-related, region-specific activation of brain structures that agrees well with published autoradiographic CB1 receptor density binding maps. Pretreatment with a CB1 antagonist but not with a CB2 antagonist, abolished these activation patterns, suggesting an effect mediated by CB1 receptors alone. In contrast, no significant changes in brain activity were found with relevant doses of the CB2 selective agonist. Conclusion and implications: These results provide the first clear evidence for quantifying in vivo functional selectivity between CB1 and CB2 receptors using phMRI. Further, as the presence of CB2 receptors in the brain remains controversial, our data suggest that if CB2 receptors are expressed, they are not functional under normal physiological conditions. British Journal of Pharmacology (2008) 153, 367,379; doi:10.1038/sj.bjp.0707506; published online 29 October 2007 [source]

The management of cancer pain,

CA: A CANCER JOURNAL FOR CLINICIANS, Issue 2 2000
Dr. 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 Relief

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2000
MacDonald 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]

Oral hypertonic glucose spray: a practical alternative for analgesia in the newborn

ACTA PAEDIATRICA, Issue 10 2004
M Akçam
Aim: Pain and stress have been shown to induce significant physiological and behavioural reactions in newborn infants. Pharmacological agents are not recommended in neonates for pain relief in minor procedures. Since different sweet solutions given orally by syringe have been shown to relieve pain in neonates, we decided to compare the analgesic effects of a small dose of glucose solution given orally by spray and by syringe during heel lancing in term neonates, using a validated behavioural acute pain rating scale. Methods: Sixty hyperbilirubinaemic full-term neonates were studied. We used a randomized, masked, placebo-controlled, crossover trial. Each infant was assessed three times receiving 0.5 ml 30% glucose in spray form, 0.5 ml 30% glucose by syringe or 0.5 ml sterile water by syringe in random order, 2 min before heel lancing. Results: Pain scores were significantly lower in the 30% glucose given either spray or syringe groups compared with the placebo group. No statistically significant difference in pain scores was found between the 30% glucose spray group and 30% glucose syringe group. Conclusions: A small dose of 0.5 ml 30% glucose spray has an equal analgesic effect to the same dose given by syringe. The spray form has the advantage of being easy to use and is well accepted by newborn babies. [source]