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)

Morphine and aspartic acid were administered separately and in combination to 80 rats divided into 8 groups. Ten and 20 min following the injections, brain, liver and kidney L-asparaginase activity was determined. Morphine decreased brain and liver L-asparaginase activity and increased that of kidney. Aspartic acid completely antagonized the effect of morphine. Additionally 500 IU/kg L-asparaginase and 5 or 10 mg/kg morphine were i.v. injected into 56 rats divided into 5 groups. L-Asparaginase, which, in turn, increased motor activity, antagonized the morphine-induced hypoactivity and analgesia. These results support our previous findings.
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PMID:The relationship between morphine, aspartic acid and L-asparaginase in rats. 52 70

The effects of the specific N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 (dizocilpine, 0.075 mg/kg, i.p.) on swim-stress-induced analgesia (SSIA) were studied in control (C) mice and in mice selectively bred for high (HA) or low (LA) SSIA. In three consecutive experiments, animals were subjected to forced swimming at water temperature of 20 degrees C, 32 degrees C and 15 degrees C and the resulting analgesia (hot-plate test) was found to be mixed opioid/non-opioid, opioid and non-opioid, respectively, as a function of the degree of antagonism by naloxone (10 mg/kg, i.p.). The major finding of this study is that MK-801 attenuated 15 degrees C SSIA, against which naloxone was ineffective, but had no effect on 32 degrees C SSIA, which naloxone blocked completely. A combination of naloxone and MK-801 significantly attenuated 20 degrees C SSIA in C and HA mice and in HA mice this attenuation was significantly larger than that produced by either drug alone. Morphine analgesia (10 mg/kg, i.p.) was unaffected by MK-801. It is concluded that low doses of MK-801 selectively block non-opioid mechanisms of SSIA.
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PMID:N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 blocks non-opioid stress-induced analgesia. II. Comparison across three swim-stress paradigms in selectively bred mice. 138 34

The effects of the specific N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 (0.075 mg/kg), and the specific opiate receptor antagonist naloxone (10 mg/kg), on swim stress-induced analgesia (SSIA) were studied in opiate receptor-deficient (CXBK) and opiate receptor-rich (CXBH) mice. Animals were subjected to forced swimming, and analgesia was assessed using the hot-plate test. In CXBK mice SSIA was blocked by MK-801 but was completely insensitive to naloxone. In CXBH mice SSIA was partially attenuated both by naloxone and MK-801, and it was nearly abolished by a combination of these drugs. Morphine analgesia (10 mg/kg) was abolished by naloxone but completely unaffected by MK-801 in CXBH mice. These findings suggest that the NMDA receptor is critically involved in the non-opioid component of SSIA.
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PMID:N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 blocks non-opioid stress-induced analgesia. I. Comparison of opiate receptor-deficient and opiate receptor-rich strains of mice. 165 62

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

To investigate the possible role of excitatory amino acids (EAAs) in the mechanisms of morphine tolerance, rats were treated either with the wide-spectrum EAA antagonist, kynurenic acid (150 mg/kg), or the specific N-methyl-D-aspartic acid (NMDA) receptor antagonist. MK-801 (0.05 mg/kg), during a four-day induction period of morphine tolerance. Morphine was given once daily at a dose of 15 mg kg. On the fifth day rats were injected only with morphine (15 mg/kg), and analgesia was assessed using the hot-plate test. Morphine tolerance was significantly reduced by both EAA antagonists. Control experiments showed that at the same doses neither acute nor chronic administration of these antagonists affected morphine analgesia itself in a manner that can explain these findings. The possible involvement of EAAs in the mechanisms of morphine tolerance is discussed.
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PMID:Excitatory amino acid antagonists (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat. 186 74

To investigate the possible involvement of enduring or delayed changes at the N-methyl-D-aspartic acid (NMDA) receptor in the mechanisms of morphine tolerance, rats were treated with the specific NMDA receptor antagonist, MK-801 (0.15 mg/kg) 2 h after morphine injection (20 mg/kg) during a 4-day induction period of tolerance. On the fifth day rats were injected only with morphine (15 mg/kg), and analgesia was assessed using the hot-plate test. Morphine tolerance was significantly reduced by MK-801. These findings suggest that long-lasting or delayed changes at the NMDA receptor underlie the development of morphine tolerance. Moreover, because MK-801 was delivered 2 h after morphine and therefore could not serve as a cue for morphine administration, these findings indicate that the attenuating effect of MK-801 on the development of morphine tolerance is not attributable to state-dependent learning.
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PMID:Delayed application of MK-801 attenuates development of morphine tolerance in rats. 193 79

The brain contains neuronal circuits, activation of which by electrical stimulation or environmental stress causes analgesia. Both opioid and non-opioid forms of stimulus-induced analgesia exist, and are anatomically differentiated. Several transmitters have been postulated for non-opioid stimulus-induced analgesia, N-methyl-D-aspartic acid being a particularly likely candidate. In mice there are marked gender differences in the underlying neurochemical medication of stress-induced analgesia, the development of which is sensitive to the hormonal environment during early post-natal development and which changes with age in both sexes. Mice can be bred for a high or low analgesic response to stress and there is evidence that this is determined by a single gene. Operative pain, as a stressor, inhibits natural killer (NK) cell activity and influences the propensity to develop metastases when mice are inoculated with an experimental tumour after abdominal surgery. This can be influenced by peri-operative morphine in analgesic doses.
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PMID:The analgesic response to stress: genetic and gender considerations. 764 37

The effects of D- and L-aspartic acids on the nociceptive tail flick reflex in mice were investigated. D-Aspartic acid (115-230 mg/kg, IP) was found to increase tail flick latency significantly. Naloxone (0.1 mg/kg) abolished the analgesic effect of D-aspartic acid (115 mg/kg). Morphine and D-aspartic acid, when combined at their nonanalgesic doses, led to significant analgesia. It may be concluded that the opioid system is involved in the antinociceptive effect of D-aspartic acid. Both morphine and D-aspartic acid were previously reported to inhibit L-aspartic acid production via blockade of L-asparaginase. L-Aspartic acid, which was ineffective alone, significantly inhibited the antinociceptive effects of both D-aspartic acid and morphine.
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PMID:Antinociceptive effect of D-aspartic acid in mice. 767 49

Effects of electrical stimulation of the somatosensory area II (S II) of the cerebral cortex and electroacupuncture (EA) on contents of r-aminobutyric acid (GABA), glutamic acid (Glu), aspartic acid (Asp) and alanine (Ala) in the precruciate cortex (PreCtx) were investigated in order to probe if the free amino acids in the preCtx are involved in the S II descending modulation and acupuncture analgesia. Adult cats were randomly divided into four groups: control, EA, electrical stimulation of S II and stimulation of S II plus EA. EA was applied at right Huantiao and Yanglingquan acupoints for 30 min and electrical stimulation was given on the S II surface. Amino acids were separated by paper chromatography and determined with spectrophotometry. Results showed that the stimulation of S II or/and EA had no significant effects on the contents of GABA, Glu, Asp and Ala in the PreCtx, indicating that the four amino acids are probably not involved in regulatory effects of EA and the stimulation of S II on the PreCtx.
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PMID:[Effects of electrical stimulation of S II and electroacupuncture on contents of some free amino acids in the precruciate cortex]. 783 61

The present study was performed to examine the analgesic effects of the intrathecal administration of agents acting at various sites in the N-methyl-D-aspartic acid (NMDA) receptor complex on the nociceptive responses to s.c. formalin injection in rats. Both the competitive NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) and the non-competitive NMDA antagonist dizocilpine maleate (MK-801) produced dose-dependent analgesic effects in the late, but not the early, phase of the formalin test. The polyamine antagonist ifenprodil, and the strychnine-insensitive glycine antagonists DCQX and 7-chlorokynurenic acid, failed to produce any analgesic effects in either the early or the late phase of the formalin test. The analgesic effects of APV were enhanced slightly by combined administration with a non-analgesic dose of glycine, and the analgesic effects of MK-801 were dramatically potentiated by combined administration of a non-analgesic dose of the polyamine spermine. The results indicate that much more potent analgesia can be produced in the formalin test by a combination of open channel blockers (such as MK-801) with agonists acting at the polyamine site, than by a single treatment with antagonists to either glycine allosteric or polyamine sites within the NMDA receptor complex.
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PMID:Potent analgesia induced in rats by combined action at PCP and polyamine recognition sites of the NMDA receptor complex. 790 88


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