Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recent literature on the antinociceptive action of ionotropic glutamate receptor antagonists is reviewed with special emphasis on their clinical potential. Actually the glutamatergic pathways descending from the brain stem into the spinal cord may generate analgesia. However, physiologically more important is that glutamate and aspartate are apparently the main neurotransmitters along the ascending nociceptive pathways in the spinal cord. Glutamate, aspartate and their receptors can be detected in particularly high concentrations in the dorsal root ganglia and the superficial laminae (I, II) of the spinal cord. In low doses glutamate receptor antagonists only slightly elevate the threshold of the physiological pain sensation. However, they suppress the process of pathological sensitisation i.e. lowering of the pain threshold seen upon excessive or lasting stimulation of C-fibre afferents, a process that takes place during inflammation or other kinds of tissue injury. At electrophysiological level antagonists of both the NMDA- and AMPA/kainate receptors inhibit wind up i.e. lasting activation of the polymodal, second-order sensory neurones in the deeper layers of the dorsal horn. During sensitisation the resting Mg(++) blockade of transmembrane Ca(++) channels is abolished, certain second messenger pathways are activated, the transcription of many genes is enhanced leading to overproduction of glutamate and other excitatory neurotransmitters and expression of Na(+) channels in the primary sensory neurones activated at lower level of depolarisation. This cascade of events leads to increased excitability of the pain pathways. NMDA antagonists are apparently more potent in experimental models of neuropathic pain, whereas AMPA antagonists are more effective in abolition of hyperalgesia seen during experimental inflammation. Clinically, of the previously known NMDA antagonists amantadine, dextromethorphan and ketamine have been tested, the latter extensively. Ketamine has been found quite active in certain cases of neuropathic pain and it reduced the opiate demand when used for postoperative analgesia. However, in other types of clinical pain their efficacy is less convincing. Not being registered there are no clinical data on the AMPA antagonists. There are, however, some investigational new drugs and some novel compounds in the stage of preclinical development which antagonise the AMPA receptors in competitive fashion or allosterically. Of the latter molecules 2,3-benzodiazepines are particularly promising.
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PMID:The role of ionotropic glutamate receptors in nociception with special regard to the AMPA binding sites. 1194 38

Hemodynamic profiles and myocardial contractility were investigated in children aged 3-14 years during epidural anesthesia with propofol. Anesthesia was induced by intravenous bolus propofol (3.5 mg/kg). Ketamine (2.4 mg/kg) was used to potentiate analgesia during intubation. Xilocaine (5 mg/kg) was used for epidural analgesia. Anesthesia was maintained by continuous i.v. propofol infused in a dose of 191-312 micrograms/kg x min (mean dose 243 +/- 30.3 micrograms/kg x min) until the peak of epidural analgesic activity was reached, after which propofol dose was gradually reduced to 53-143 micrograms/kg x min (mean 108.8 +/- 14.6 micrograms/kg x min). This variant of epidural anesthesia with i.v. propofol ensured a hemodynamically stable anesthesia and good analgesia in operations of any complexity. It was however paralleled by a moderate decrease of myocardial contractility.
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PMID:[Changes in hemodynamics with a combination of epidural anesthesia and propofol sedation in children]. 1199 92

Owing to different mechanisms of analgesia, we hypothesized that the combination of ketamine and tramadol could produce synergistic or additive antinociceptive effects. Swiss albino mice were administered intraperitoneally with ketamine, tramadol, a combination of ketamine and tramadol, or saline, and the resulting antinociceptive effects were tested in the mouse tail-flick and formalin tests. The potencies of the two drugs alone or in combination were obtained by fitting data to the Sigmoid Emax equation. Isobolographic analysis was performed to evaluate the interaction. CNS depression was also monitored. Results showed that tramadol exhibited apparent dose-dependent effects in the tail-flick test, and in phase 1 and phase 2 of the formalin test. Ketamine dose-dependently inhibited the phase 2 responses, but failed to modify the phase 1 and tail-flick responses. Combination of tramadol and ketamine produced significant synergistic interactions only in phase 2 of the formalin test (P < 0.05). The synergistic combinations also displayed less CNS depression than when an equianalgesic dose of ketamine was administered alone. We conclude that in the acute thermal or chemical pain model, ketamine is not effective and the net effect of ketamine and tramadol in combination was simply additive after systemic administration. However, the coadministration produced synergistic antinociception in the chemical-induced persistent pain model.
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PMID:Isobolographic analysis of the analgesic interactions between ketamine and tramadol. 1200 57

We present a rare case of an autoerotic accident involving a fatal combination of asphyxia by suffocation and intoxication with self-administered intravenous ketamine. Of note in this case is the fact that the victim was an emergency medical technician. Ketamine causes complete analgesia with superficial unconciousness and amnesia called "dissociative anasthesia". Futhermore low anaesthetic doses of ketamine induce alterations in mood, cognition and body image and the substance is an emerging drug of abuse. We discuss the death scene investigation, findings at autopsy and the toxicological report.
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PMID:Autoerotic accident associated with self-applied ketamine. 1205 18

Epidural opioids have been reported to provide superior analgesia in acute pain management. Despite the fact that the required doses are low, major side effects such as respiratory depression may still occur. In an effort to maximize analgesia and to minimize the rate of side effects, epidural NMDA receptor antagonists, especially ketamine, may be co-administered with opioids. This study investigated whether ketamine had beneficial effects on fentanyl- or morphine-induced antinociception in an acute pain model in rats. In male Wistar rats, an epidural catheter was placed under general anaesthesia. After 1 week the animals were subjected to the tail withdrawal reaction (TWR) test. After determination of the basal reaction latencies, fentanyl, morphine, ketamine or combinations of an opioid with ketamine were administered epidurally. TWR latencies were measured for up to 2h after treatment. Both opioids showed a dose related antinociceptive effect. Fentanyl had a fast onset and a short duration of action whereas the reverse was true for morphine. Ketamine exhibited only limited antinociceptive properties. In the combinations, ketamine improved morphine-induced antinociception both in terms of maximal possible effect (MPE) as well as in duration of action. The combination of fentanyl with ketamine did not result in any improvement, neither in terms of MPE nor in duration of action. Moreover, increasing doses of ketamine tended to decrease the MPE of various doses of fentanyl. These data confirm that ketamine, contrary to opioids, does not possess important antinociceptive properties in an acute test such as the TWR test. Furthermore, these data indicate that additive drugs such as ketamine may have different effects on different opioids.
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PMID:Epidural ketamine potentiates epidural morphine but not fentanyl in acute nociception in rats. 1260 Jul 93

Ketamine is an NMDA receptors antagonist, with a potent anaesthetic effect. NMDA receptors are involved in nociceptive modulation, in the wind-up phenomenon, in peripheral receptive fields expansion, in primary and secondary hyperalgesia, in neuronal plasticity. Ketamine effects are well-known: it produces a state of "dissociative anaesthesia", amnesia, and, at the same time, it mantains the respiratory drive effective and supports the sistemic arterial blood pressure. Anaesthesiologists are also familiar with its side-effects, like the increase of salivar and bronchial secretions, the possible increase of intracranial and pulmonary pressures and the dysphoric effect that may produce vivid and sometimes unpleasant dreams. Reviewing scientific data and studies about the use of ketamine in children, many considerations come out: at first they considered the effects of the racemic ketamine, then they evaluated the S-enantiomer. Many surveys studied the effects (analgesia, sedation, side-effects) of different doses or different routes of administration. Other studies were designed to compare ketamine to clonidine or opioids as adjuvants in paediatric regional anaesthesia with local anesthetic drugs, in order to prolong analgesia. In our Children's Hospital, we use ketamine in the operating room, in intensive care unit and for any procedure in hospital wards. The suggested doses are: Epidural or caudal route (as an ajuvant for local anaesthetic agents, in the treatment of postoperative pain): 0.5 mg/kg. Sedative/analgesic effect (for algesic procedures): 1-2 mg/kg i.v. Continuous infusion (intensive care unit): 0.5 mg/kg/h, with a range from 20-30 microg/kg/min to 80 microg/kg/min, depending on the age of the patient.
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PMID:Ketamine: a new look to an old drug. 1276 86

In a randomized, double-blinded study, we evaluated the analgesic effect of ketamine in the management of pain in a surgical intensive care unit after major abdominal surgery. Patients received morphine patient-controlled analgesia with either placebo (Group M) or ketamine (Group K). Morphine was administered with initial loading doses of 2 mg until the visual analog scale (VAS) score was <30 and thereafter with bolus doses of 1 mg and a lockout time of 7 min. Ketamine was administered with an initial bolus of 0.5 mg/kg followed by a perfusion of 2 micro g x kg(-1) x min(-1) during the first 24 h and 1 micro g x kg(-1) x min(-1) during the following 24 h. The 4-h cumulative morphine doses were measured over 48 h. The VAS scores at rest and at mobilization were measured every 4 h during 48 h. A total of 101 patients were enrolled, and 93 were analyzed (41 in Group K and 52 in Group M). VAS scores at rest and at mobilization were similar. The cumulative consumption of morphine was significantly smaller in Group K (P < 0.05). We concluded that small doses of ketamine were a valuable adjunct to opioids in surgical intensive care unit patients after major abdominal surgery.
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PMID:The effects of small-dose ketamine on morphine consumption in surgical intensive care unit patients after major abdominal surgery. 1293 13

The present study was designed to test the hypothesis that a synergistic interaction could be recorded after epidural administration of ketamine-an N-methyl-D-aspartate (NMDA) antagonist and pethidine--an opioid agonist. Twelve adult mongrel dogs of either sex were randomly divided in three groups A, B and C of four animals each. Ketamine (5%) at 2.5 mg/kg and pethidine (3%) 2 mg/kg were injected at lumbosacral epidural space in animals of groups A and B, respectively. In animals of group C ketamine (2.5 mg/kg) and pethidine (2 mg/kg) were injected. Heart rate increased significantly up to 15 min in group A, whereas in groups B and C, the increase was non-significant for a period of 10 and 45 min, respectively. Respiration increased gradually up to 45-60 min in group A and for 15-20 min in group B. However, in animals of group C respiration fell below the baseline during the first 10-15 min and then returned near the baseline. Rectal temperature decreased only marginally in all the groups. Ketamine alone produced complete analgesia at tail and perineal region for a period of 5-10 min and then moderate analgesia for the next 20-30 min. Analgesia at the flank was moderate to complete between 5 and 15 min. In group B complete analgesia was only moderate at the tail and perineal region up to 30 min. In animals of group C, complete analgesia was observed only at perineal region for a very short period (5 min). Analgesia was not associated with sedation in any of the groups but animals of groups A and C showed signs of motor incoordination. Results of the study suggest rather antagonistic than synergistic interaction between epidurally administered ketamine and pethidine. Further studies are needed to confirm the antagonistic interaction between the two drugs.
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PMID:Interaction between epidurally administered ketamine and pethidine in dogs. 1456 13

Few studies exist of using remifentanil and intravenous ketamine for anaesthetic induction in paediatric day case anaesthesia. Therefore, we studied 75 unpremedicated ASA I-II children (age 1-7 years) who were randomly assigned in a double-blind fashion to receive either remifentanil (1 microgram/kg), ketamine (0.7 mg/kg) or placebo before the anaesthetic induction. Anaesthesia was induced with propofol and maintained with O2-N2O-sevoflurane. Induction characteristics, recovery times and the need for postoperative analgesia were evaluated. The required induction dose of propofol was lower in the groups receiving remifentanil and ketamine compared with the group receiving placebo. After tracheal intubation heart rate and blood pressure were better attenuated with remifentanil than with ketamine or placebo. In the recovery room children in the placebo group required more doses of oxycodone than the other two groups but this did not reach statistical significance. There were no differences between the groups in achieving predetermined recovery end-points, attaining full points on the Steward score or in the well being at home. In conclusion, remifentanil provides haemodynamically more stable induction of anaesthesia compared with ketamine or placebo. Ketamine with its' longer duration of action does not prolong recovery but does not have a clear opioid-sparing effect either in the immediate postoperative period.
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PMID:Comparison of remifentanil versus ketamine for paediatric day case adenoidectomy. 1459 18

Ketamine has diverse effects that may be of relevance to chronic pain including: N-methyl-D-aspartic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, gamma-aminobutyric acid(A) receptors; inhibition of voltage gated Na(+) and K(+) channels and serotonin, dopamine re-uptake. Ketamine has been in clinical practice for over 30 yr; however, there has been little formal research on the effectiveness of ketamine for chronic pain management. In this review we evaluate the available clinical data as a basis for defining the potential use of ketamine for chronic pain. Literature referenced in this review was obtained from a computer search of EMBASE and MEDLINE from 1966 through August, 2002. Search terms included ketamine, ketalar, pain, painful, analgesic, and analgesia. Abstracts were screened for relevance and publications relating to chronic pain use were obtained. Levels of evidence were stratified according to accepted guidelines (level I-IV). For central pain, there is level II and level IV evidence of efficacy for parenteral and oral ketamine. For complex regional pain syndromes, there is only level IV evidence of efficacy of epidural ketamine. For fibromyalgia, there is level II evidence of pain relief, reduced tenderness at trigger points, and increased endurance. For ischemic pain, a level II study reported a potent dose-dependent analgesic effect, but with a narrow therapeutic window. For nonspecific neuropathic pain, level II and level IV studies reported divergent results with questionable long-term effects on pain. For phantom limb pain and postherpetic neuralgia, level II and level II studies provided objective evidence of reduced hyperpathia and pain relief was usually substantial either after parenteral or oral ketamine. Acute on chronic episodes of severe neuropathic pain represented the most frequent use of ketamine as a "third line analgesic," often by IV or subcutaneous infusion (level IV). In conclusion, the evidence for efficacy of ketamine for treatment of chronic pain is moderate to weak. However, in situations where standard analgesic options have failed ketamine is a reasonable "third line" option. Further controlled studies are needed.
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PMID:Ketamine in chronic pain management: an evidence-based review. 1463 51


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