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)

Repetitive stimulation of small diameter primary afferent fibres produces a progressive increase in action potential discharge (windup) and a prolonged increase in the excitability of neurones in the spinal cord following the stimulus. Previous studies have demonstrated that windup is the consequence of the temporal summation of slow synaptic potentials and that the slow potentials and windup are reduced by pretreatment with N-methyl-D-aspartic acid (NMDA) antagonists. We have now examined whether primary afferent induced hypersensitivity states in flexor motoneurones are also dependent on the activation of NMDA receptors and whether windup is a possible trigger for the production of the central hypersensitivity. Both a non-competitive (MK-801) and a competitive (D-CPP) NMDA antagonist, at doses that did not modify the baseline reflex, reduced the facilitation of the flexor reflex produced by either brief electrical stimulation of the sural nerve (1 Hz for 20 sec at C-fibre strength), or by the cutaneous application of the chemical irritant mustard oil. These antagonists also prevented windup from occurring in the motoneurones. When the the MK-801 and the D-CPP were administered once a state of central facilitation had been induced by prior treatment with mustard oil, they returned the facilitated reflex to its pretreatment level. These results indicate that NMDA receptors are involved in the induction and maintenance of the central sensitization produced by high threshold primary afferent inputs. Because central sensitization is likely to contribute to the post-injury pain hypersensitivity states in man, these data have a bearing both on the potential role of NMDA antagonists for pre-emptive analgesia and for treating established pain states.
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PMID:The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. 1256 Mar 18

Rats were given morphine as an agent of putative conditioning to establish a place preference. Doses of 4 and 8 mg/kg of morphine did establish reliable conditioned place preferences (CPP's). Other rats were given one of the doses of morphine and one of a number of antagonists in procedures designed to assess which antagonists would specifically block morphine's ability to establish a CPP indicative of positivity. Doses of naloxone and larger doses of naltrexone but not smaller ones did antagonize morphine's effects. A dose of the benzodiazepine antagonist Ro 15-1788 did not attenuate morphine's effects. It was concluded that morphine's positivity is dependent upon actions by way of receptors sensitive to naloxone and naltrexone, but that morphine's positivity is less sensitive to naltrexone's effects than morphine's analgesia.
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PMID:Using antagonists to assess neurochemical coding of a drug's ability to establish a conditioned place preference. 208 83

The effects of NMDA antagonists on passive avoidance learning, shock sensitivity and locomotor activity were examined. Pre-training administration of the antagonists 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) in mice and rats resulted in impaired performance in a retention test 24 h later. No such impairment resulted from immediate post-training administration of either compound in either species. In addition neither compound, given only before the retention test, reduced the retention latencies of mice. In rats CPP was similarly ineffective whereas MK-801 reduced retention latencies, but only at a dose which significantly elevated locomotor activity at the time of the retention test. As assessed by vocalization threshold in mice and by the proportion of animals vocalizing in response to the passive avoidance training shock, neither compound produced analgesia. The vocalization threshold was, in fact, slightly reduced by both compounds. MK-801, but not CPP, stimulated locomotor activity in mice. These results indicate that in the passive avoidance task activation of NMDA receptors is involved in memory formation, but is not critical for the maintenance of memory or its retrieval.
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PMID:Effects of NMDA receptor antagonists on passive avoidance learning and retrieval in rats and mice. 215 33

The haemodynamic effects of isoflurane- and modified neurolept-anaesthesia were evaluated in 24 patients undergoing coronary artery bypass grafting. 12 patients (isoflurane group) were anaesthetized after an induction with 1.5 mg/kg methohexital and a unique dose of 0.005 mg/kg fentanyl with isoflurane (0.5-1.5 Vol%), N2O/O2 and pancuronium. 12 patients (neurolept group) received fentanyl (0.04 mg/kg), flunitrazepam, pancuronium and N2O/O2. Haemodynamic measurements were made before anaesthesia, in steady state anaesthesia, after sternotomy, after extracorporal circulation, after thoracic closure and one, two and four hours after the end of the operation. Between both groups we could not find significant differences in the haemodynamic parameters RAP, PAP, PCWP, PVR, CI, SVI, AP and CPP. However in the isoflurane group the peripheral vascular resistance (TPR) was significantly lower in steady state anaesthesia and after sternotomy. In the neurolept group the heart rate (HR) was significantly higher after bypass than in the isoflurane group. We believe, that at this time fentanyl analgesia was reduced. Before extracorporal bypass, patients with isoflurane anaesthesia had a lower arterio-mixed venous oxygen content difference (AVDO2) than patients with neurolept anaesthesia. Therefore it can be supposed that isoflurane lowers the oxygen demand more than neurolept anaesthesia. After surgery neurolept anaesthetized patients showed postanaesthetic shivering more frequently than those in the isoflurane group. We suggest that the vasodilating effect of isoflurane induces a homogeneous heat gain during warming the patients up, and that, therefore, in patients of the isoflurane-group AVDO2 and TPR were lower than in the patients of the neurolept-group during the first postoperative hours.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hemodynamics of coronary surgery patients under isoflurane and neuroleptanalgesia]. 375 80

The present study was performed to assess the utility of excitatory amino acid (EAA) antagonists as analgesia agents. The antinociceptive activity of various classes of EAA antagonists was assessed in mechanical and thermal flexion reflexes tests, as well as in the formalin test. Additional testing assessed the motor dysfunction associated with antinociceptive dose levels of the agents used, by examining placing, grasping and righting reflexes, as well as occurrences of balance loss during locomotion. No antinociceptive activity was observed on any of the nociceptive measures for the non-NMDA receptor antagonists CNQX or L-AP-3. High doses of the non-competitive (PCP-site) NMDA receptor antagonist MK-801 and the allosteric-glycine receptor antagonist 7-CKA produced antinociception on both the mechanical and thermal flexion reflex measures, while a high dose of the competitive NMDA receptor antagonist CPP produced antinociception only on the thermal flexion reflex measure. Hyperalgesic effects on thermal flexion reflexes were obtained with all doses of the polyamine receptor antagonist ARCA, and with the highest dose of the allosteric-glycine receptor antagonist FICA. Formalin nociceptive behaviours were significantly reduced only by high doses of competitive (APV) and non-competitive (MK-801) NMDA receptor antagonists. The doses of EAA receptor antagonists which produced antinociceptive effects on any of the 3 nociceptive tests also produced evidence of motor dysfunction. Both competitive NMDA receptor antagonists (APV and CPP) produced disruptions of placing, grasping and righting reflexes, while 2 of the allosteric-glycine receptor antagonists (7-CKA and DCQX) significantly disrupted placing and righting reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The utility of excitatory amino acid (EAA) antagonists as analgesic agents. I. Comparison of the antinociceptive activity of various classes of EAA antagonists in mechanical, thermal and chemical nociceptive tests. 770 8

Effects of the non-selective 5-hydroxytryptamine (5-HT) receptor agonist m-chlorophenylpiperazine (m-CPP) on the nociceptive responsiveness in a hot plate and tail flick tests were examined in mice. Intraperitoneal administration of m-CPP (1-10 mg/kg) produced a dose-dependent antinociception in both those tests; the effect of m-CPP in the hot plate test was stronger. The antinociceptive effect of m-CPP in either test was abolished by pretreatment with mesulergine (2 mg/kg), ritanserin (1-2 mg/kg), 5-HT2A/5-HT2C receptor antagonists, and metergoline (0.5-2 mg/kg), a non-selective 5-HT receptor antagonist. On the other hand, spiperone (0.25-0.5 mg/kg), a dopamine, 5-HT1A and 5-HT2A receptor antagonist; pindolol (4-8 mg/kg), a beta-adrenoceptor, 5-HT1A and 5-HT1B receptor antagonist and zacopride (0.1-1 mg/kg) a 5-HT3 receptor antagonist, did not affect the analgesia induced by m-CPP. Neither of the drugs used as putative receptor antagonists changed the nociceptive responsiveness in mice. The obtained results suggest that the analgesia induced by m-CPP is mediated by 5-HT2C receptors.
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PMID:Involvement of 5-HT2C receptors in the m-CPP-induced antinociception in mice. 789 29

Despite opioids are routinely used for analgesia in head injured patients, the effects of such drugs on ICP and cerebral hemodynamics remain controversial. Cerebrovascular autoregulation (CAR) could be an important factor in the ICP increases reported after opioid administration. In order to describe the effects on intracranial pressure of fentanyl and correlated such effects with autoregulation status, we studied 30 consecutive severe head injury patients who received fentanyl (2 micrograms/kg) intravenously over one minute. Prior to study, CAR was assessed. Monitoring included MAP, HR, SaO2, ETCO2, SjO2 and ICP. Changes in cerebral blood flow (CBF) were estimated from relative changes in AVDO2. Patients mean GCS was 5.7 +/- 1.7 (mean +/- STD) and mean ICP on admission was 23.8 +/- 16.3 mmHg. Fentanyl caused significant increases in ICP and decreases in MAP and CPP, but CBF remained unchanged when estimated by AVDO2. In patients with preserved CAR (34.5%), opioid-induced ICP increase was greater (but not statistically significant) than in those with impaired CAR (65.5%). We conclude than fentanyl moderately increased ICP and decreased MAP and CPP. Our data suggests that in patients with preserved CAR, potent opioids could cause greater increases of ICP, probably due to activation of the vasodilatadory cascade.
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PMID:Effects on intracranial pressure of fentanyl in severe head injured patients. 977 29

The intrathecal (IT) administration of NMDA in rodents has usually been reported to produce hyperalgesic reactions, although some articles describe that spinal NMDA can lead to analgesia. We show here that the nociceptive behavior (biting, scratching, licking; BSL) observed after NMDA injection (1-8 microg/rat; IT) is followed by a long period of increased tail-flick latencies, not longer detected 24 h after NMDA administration. The NMDA-receptor antagonist CPP (10-100 ng/rat; IT) blocked the BSL behavior induced by NMDA. In the tail-flick test, this antagonist induced analgesia by itself, and was able, at 30 ng/rat, to prevent the NMDA-mediated analgesia. The implication of opiate mechanisms was discarded since naloxone (3 and 10 mg/kg; IP) did not antagonize NMDA-induced analgesia. Finally, the involvement of the intracellular calcium binding protein calmodulin was assessed. The calmodulin inhibitor, calmidazolium (30-300 microg/rat; IT) only blocked the excitatory effect (BSL) without modifying the tail-flick analgesia produced by NMDA (4 microg). These results show that a single intrathecal administration of NMDA sequentially induces both nociceptive and antinociceptive, nonopiate responses in rats.
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PMID:Intrathecal N-methyl-D-aspartate (NMDA) induces paradoxical analgesia in the tail-flick test in rats. 1076 14

Multiple studies demonstrate that coadministration of N-methyl-D-aspartate (NMDA) receptor antagonists with the opioid agonist morphine attenuates the development of analgesic tolerance. Sex differences in the effects of noncompetitive, but not competitive NMDA receptor antagonists on acute morphine analgesia, have been reported in mice, yet the role of sex in modulation of morphine tolerance by NMDA receptor antagonists has yet to be addressed. Therefore, we tested whether there is a sex difference in the effect of NMDA receptor antagonists on the development of morphine analgesic tolerance in C57BL/6J mice. Acutely, at a dose required to affect morphine tolerance in male mice, the noncompetitive NMDA receptor antagonist dizocilpine (MK-801) prolonged morphine analgesia similarly in both sexes in the hot plate and tail withdrawal assays. In the hot plate assay, coadministration of MK-801 or the competitive antagonist 3-(2-carboxpiperazin-4-yl)propyl-1-phosphanoic acid (CPP) with morphine attenuated the development of tolerance in male mice, while having no effect in females. Like normal and sham females, ovariectomized mice were similarly insensitive to the attenuation of morphine tolerance by MK-801 in the hot plate assay. Surprisingly, in the tail withdrawal assay, MK-801 facilitated the development of morphine-induced hyperalgesia and tolerance in males but not females. The results demonstrate that male mice are more sensitive to modulation of nociception and morphine analgesia after repeated coadministration of NMDA receptor antagonists. Furthermore, the underlying mechanisms are likely to be different from those mediating the sex difference in the modulation of acute morphine analgesia that has previously been reported.
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PMID:NMDA receptor antagonism disrupts the development of morphine analgesic tolerance in male, but not female C57BL/6J mice. 1660 Dec 58

We tested the role of sex chromosome complement and gonadal hormones in sex differences in several different paradigms measuring nociception and opioid analgesia using "four core genotypes" C57BL/6J mice. The genotypes include XX and XY gonadal males, and XX and XY gonadal females. Adult mice were gonadectomized and tested 3-4 weeks later, so that differences between sexes (mice with testes vs. ovaries) were attributable mainly to organizational effects of gonadal hormones, whereas differences between XX and XY mice were attributable to their complement of sex chromosomes. In Experiment 1 (hotplate test of acute morphine analgesia), XX mice of both gonadal sexes had significantly shorter hotplate baseline latencies prior to morphine than XY mice. In Experiment 2 (test of development of tolerance to morphine), mice were injected twice daily with 10 mg/kg morphine or saline for 6 days. Saline or the competitive NMDA antagonist CPP (3-(2-carboxypiperazin-4yl) propyl-1-phosphonic acid) (10 mg/kg) was co-injected. On day 7, mice were tested for hotplate latencies before and after administration of a challenge dose of morphine (10 mg/kg). XX mice showed shorter hotplate latencies than XY mice at baseline, and the XX-XY difference was greater following morphine. In Experiment 3, mice were injected with morphine (10 mg/kg) or saline, 15 min before intraplantar injection of formalin (5%/25 microl). XX mice licked their hindpaw more than XY mice within 5 min of formalin injection. The results indicate that X- or Y-linked genes have direct effects, not mediated by gonadal secretions, on sex differences in two different types of acute nociception.
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PMID:Sex chromosome complement affects nociception in tests of acute and chronic exposure to morphine in mice. 1795 59


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