Biomedical subjects

P Marek

Publications and source records attributed to P Marek.

At least 37 records · Page 2Linked to original sources

PubMed1992

Stress-induced analgesia prevents the development of the tonic, late phase of pain produced by subcutaneous formalin.

Subcutaneous injection of formalin produces a biphasic pain response: a transient early phase followed by a tonic late phase. It has recently been suggested that development of the late phase depends upon the presence of the early one. In support of this suggestion, we now demonstrate that blocking the early phase by stress-induced analgesia prevents development of the late phase, whereas the same stressor given after the first phase does not. Both phases are manifested when stress-induced analgesia is blocked by the N-methyl-D-aspartate (NMDA) or opiate antagonists, MK-801 and naloxone.

Analgesia↗

PubMed1992

The effect of phencyclidine and DL-2-amino-5-phosphonovaleric acid on N-methyl-D-aspartic acid induced changes in extracellular concentration of dopamine and DOPAC in the rat neostriatum.

The effects of N-methyl-D-aspartic acid (NMDA) and phencyclidine (PCP) on extracellular levels of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) in the striatum of the rat were studied using in vivo microdialysis. Intrastriatal infusion of NMDA produced a significant dose-dependent increase in extracellular DA and a decrease in concentrations of DOPAC. Whereas both 2-amino-5-phosphonovalerate (APV) and PCP antagonized the NMDA-induced increase in extracellular levels of DA, the effect on NMDA-induced changes in extracellular concentrations of DOPAC were different for the two compounds. The APV significantly attenuated the decrease in extracellular DOPAC produced by smaller concentrations of NMDA, whereas PCP did not prevent decrease in DOPAC produced by any concentrations of NMDA. Phencyclidine alone produced a dose-dependent increase in extracellular DA but had no effect on the extracellular concentration of DOPAC. This study demonstrated that PCP, at concentrations which did not produce an increase in extracellular DA, antagonized the effect of the NMDA on DA. The data also indicated that both APV and PCP antagonized the NMDA-evoked release of DA over a range of concentrations of NMDA, even though they did so by different mechanisms.

2-Amino-5-phosphonovalerate↗

PubMed1991

Delayed application of MK-801 attenuates development of morphine tolerance in rats.

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.

Analysis of Variance↗

PubMed1991

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.

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.

Analysis of Variance↗

PubMed1991

Excitatory amino acid antagonists (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat.

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.

Analgesia↗

PubMed1991

Stimulation-produced analgesia in the mouse: evidence for laterality of opioid mediation.

The effect of naloxone on periaqueductal gray matter (PAG) stimulation-produced analgesia (SPA) was examined in pentobarbital anesthetized Swiss-Webster mice. Electrodes were placed either in dorsolateral or ventrolateral PAG, and SPA threshold was assessed using the hind paw-flick test (paw withdrawal from radiant heat). SPA threshold did not differ between dorsal and ventral PAG, and naloxone equally attenuated SPA from both areas. SPA threshold for the paw contralateral to the stimulation site was half that for the ipsilateral paw. Elevation of SPA threshold by naloxone was greater for the contralateral than ipsilateral paw. Exposure to analgesic neck pinch prior to SPA almost completely abolished the antinociceptive effect of contralateral PAG stimulation without affecting SPA on the ipsilateral paw. This effect of pinch was itself reversed by prior naloxone administration. We suggest that the substrate of opioid mediated SPA from PAG in the mouse has principally a contralateral organization.

Analgesia↗

PubMed1991

Tolerance and cross-tolerance with morphine in mice selectively bred for high and low stress-induced analgesia.

Mice selectively bred for high (HA) and low (LA) swim-induced analgesia were exposed to two different stress paradigms; one consisting of a 3-min swim at 20 degrees C daily for 14 days, and the other consisting of 3-min swims repeated at 2-h intervals for 48 h. Both forms of chronic stress resulted in the development of tolerance to swim-induced antinociception to a greater degree in the HA mice than in control (C) mice, but were both ineffective at inducing tolerance in LA mice. Swimming repeated at 2-h intervals for 48 h resulted in cross-tolerance with morphine in HA and C mice. Naloxone (1 and 10 mg/kg, IP) failed to antagonize swim-induced analgesia in mice that had experienced chronic swimming in the 2-h/48-h paradigm. The daily swimming paradigm failed to produce cross-tolerance with morphine analgesia in any line. Differential degree of tolerance in three lines supports a hypothesis that selective breeding for high and low stress-induced analgesia has modified the degree of opioid involvement in the endogenous analgesia mechanisms.

Animals↗

PubMed1990

Stimulation of the hypothalamic paraventricular nucleus produces analgesia not mediated by vasopressin or endogenous opioids.

The analgesic effect of electrical stimulation of the hypothalamic paraventricular nucleus (PVN) was studied. Additionally, the involvement of vasopressin and opioid peptides in this process was examined by comparing vasopressin-deficient (Brattleboro) and Long-Evans rats and by administering the opiate antagonist naloxone. Rats were chronically implanted with a stimulating electrode in the parvocellular (PVN-Pc) and magnocellular (PVN-Mg) divisions of the PVN. At least 10 days after surgery, the analgesic effects of PVN stimulation were examined in lightly anesthetized rats, using the tail-flick method, and in unanesthetized rats, using the hot-plate test. PVN stimulation produced marked analgesia in both tests. Current threshold for analgesia was lower from PVN-Pc than from PVN-Mg. Threshold did not differ significantly between Brattleboro and Long-Evans rats and was not affected by naloxone administration. The results indicate that the PVN is part of the brain's pain inhibitory system, and show that the analgesia induced by PVN stimulation is not mediated by either vasopressin or opioid peptides.

Analgesia↗

PubMed1990

Genetic influences on brain stimulation-produced analgesia in mice: II. Correlation with brain opiate receptor concentration.

The analgesic effect of electrical stimulation of the periaqueductal gray matter (PAG) was studied in 4 strains of mice: C57BL/6By (C57), BALB/cBy (BALB), CXBH, and CXBK. These strains are known to have high (CXBH), low (CXBK), and intermediate (C57 and BALB) concentrations of brain opiate receptors. The current intensity required for stimulation-produced analgesia (SPA) did not differ among strains. Naloxone attenuated SPA in CXBH, C57 and BALB mice, but was ineffective in the opiate receptor deficient CXBK mice. The results suggest that genetic differences in opiate receptor density can influence the degree to which opioid mechanisms are involved in SPA from the PAG.

Analgesia↗

PubMed1990

Post-stress analgesia after lesions to the central nucleus of the amygdala in rats.

In two experiments the role of the central nucleus of the amygdala under two modes of foot-shock analgesia was studied in 39 male Möll-Wistar rats. In Experiment I a 4 min continuous foot-shock, dependent on neural mechanism was used as a stressor. Analgesia was produced by regularly intermitted 20 min of foot-shock action in Experiment II which evoke an opioid, humorally mediated mechanism. The results suggested that the central nucleus is involved only in the humoral regulation of the opioid form of analgesia. This finding fits well with the concept of limbic control of the anterior pituitary and the pituitary-adrenocortical axis, and points to the role of the amygdaloid complex in processing of stressful stimuli.

Amygdala↗

PubMed1989

Genetic influences on brain stimulation-produced analgesia in mice. I. Correlation with stress-induced analgesia.

The analgesic effect of electrical stimulation of the periaqueductal gray matter (PAG) was studied in mice selectively bred for high and low stress-induced analgesia (HA and LA lines, respectively). The current intensity required for stimulation-produced analgesia (SPA) in LA mice was 5 times that for HA mice. Naloxone produced a 4-fold increase of SPA threshold in HA mice, but was ineffective in LA mice. These findings suggest that the differential responsiveness of these two lines to the analgesic effect of stress reflects a more general genetic modification of the efficacy and mechanism of their pain-inhibitory systems.

Analgesia↗

PubMed1988

Strain differences in the magnitude of swimming-induced analgesia in mice correlate with brain opiate receptor concentration.

Swimming-induced analgesia was studied in 4 strains of mice differing in central opiate receptor density: C57BL/6By (C57), BALB/cBy (BALB/c), CXBK and CXBH. The degree of 'swim analgesia' significantly differed among strains in the order CXBH greater than BALB/c = C57 greater than CXBK. This order positively correlates with known differences in opiate receptor density in these strains. Naloxone reversed the analgesic effect of swimming in CXBH, C57 and BALB/c, but was ineffective in opiate receptor-deficient CXBK mice. These results suggest that genetic differences in central opiate receptor density influence the analgesic response to stressful stimuli.

Analgesia↗

PubMed1987

Adrenalectomy and dexamethasone differentially affect postswim antinociception in mice selectively bred for high and low stress-induced analgesia.

The effects of dexamethasone and naloxone on analgesia induced by swimming (3 min, 20 degrees C) were studied in the 6th and 7th generations of adrenalectomized and intact mice selectively bred for high (HA) and low (LA) postswim analgesia. Swim-induced analgesia in intact HA animals was significantly reduced by naloxone and dexamethasone while in LA mice these two compounds were ineffective. Naloxone ability to reverse adrenalectomy-caused swim analgesia increase was much greater in HA than in LA mice. In both intact and adrenalectomized HA animals dexamethasone and naloxone decreased postswim analgesia to the level observed in LA mice. It is suggested that selective breeding for high and low swim analgesia modified the extent of pituitary-adrenal axis involvement in the generation of stress-induced analgesia.

Adrenalectomy↗

PubMed1987

Selective breeding of mice for high and low swim analgesia: differential effect on discrete forms of footshock analgesia.

Selective breeding of mice displaying high and low swim-induced analgesia led to the development of two animal lines divergent in the magnitude of analgesic response to swimming. In this study, animals belonging to the seventh generation of both lines were exposed to two temporally different forms of footshock, one of which produced opioid and the other non-opioid analgesia. We found that selective breeding for high and low swim-induced analgesia exerted a striking influence on the magnitude of the opioid-mediated type of footshock analgesia, but was ineffective on that of the non-opioid type.

Animals↗

PubMed1987

Emergency percutaneous coronary dilatation for acute myocardial infarction in Behçet's disease.

We describe a young man with Behçet's disease who presented with acute coronary insufficiency: emergency coronary arteriography revealed 2 coronary aneurysms and a left anterior descending (LAD) artery stenosis which was successfully dilated. The reduction of the coronary stenosis by balloon angioplasty induced immediate relief of chest pain and decrease of ST segment elevation, and was probably responsible for the satisfactory evolution, with limited myocardial infarction on the ECG and no akinetic segment on the left ventricular angiogram 3 weeks after the acute event. Cardiac surgery was performed to avoid possible relapse or aneurysmal rupture with hemopericardium. Surgery confirmed the destructive arterial lesion of Behçet's disease with false aneurysms of the LAD and left circumflex arteries.

Adult↗

PubMed1986

Inheritance of stress-induced analgesia in mice. Selective breeding study.

Random mated Swiss mice swam for 3 min at 20 degrees C. The animals with less than or equal to 10 s and greater than or equal to 50 s postswim latencies on the hot plate (56 degrees C) were selected as progenitors of low (LA) and high (HA) analgesia lines, respectively. Gradual divergence of latency distributions and postswim hind paw flick latencies between the two lines was observed in successive generations. As shown by the tail flick test applied to the sixth offspring generation, postswim analgesia in the HA line was not only more pronounced but also lasted longer compared to the LA line and the unselected controls. Possible differentiation of the endorphin system activity in the course of selection is discussed.

Animals↗

PubMed1986

Differentiation of neurochemical basis of stress-induced analgesia in mice by selective breeding.

Two selectively bred lines of mice, one responding with high (HA) and the other with low analgesia (LA) to 3 min swims at 20 degrees C were compared with respect to naloxone ability to reverse such swim induced pain threshold elevation. Also, the analgesic effect of morphine was tested in both lines of mice. Naloxone at a dose of 1 mg/kg significantly reduced postswim analgesia determined with hot plate and tail flick tests in HA mice, but was not effective in LA mice. HA mice responded with significant elevation of hot plate threshold to 0.1 mg/kg of morphine hydrochloride, whereas in LA mice comparable level of analgesia developed after 12.8 mg/kg. The data argue for greater involvement of opioid mechanisms in producing analgesia in HA mice than in LA mice, and so for inheritance of endorphin system(s) activity.

Animals↗

PubMed1986

Activation of anti- and pro-nociceptive mechanisms by front paw shock in spinal mice: involvement of humoral factors.

The effect of prolonged, intermittent front paw shock on nociception was studied in two groups of differently spinalized mice. The animals, spinalized so that the dura was left intact to allow free cerebrospinal fluid (CSF) passage, exhibited post-foot shock increase in latencies of spinally-mediated nociceptive reflexes. This anti-nociception was completely blocked by naloxone. A facilitation of nociceptive reflexes was observed in animals in which the spinal cord was ligated together with the dura. The results indicate that: front paw shock in mice leads to activation of supraspinal sites which mediate anti-nociception by releasing substance(s) reaching the spinal cord via the CSF route; single stressors may simultaneously activate both anti- and pro-nociceptive mechanisms.

Animals↗