PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “morphine tolerance”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1998

Use of methadone in the morphine-tolerant burned paediatric patient.

We describe the successful use of methadone in the restoration of sedation and provision of analgesia in two morphine-tolerant, paediatric patients who had suffered significant thermal injuries and were undergoing mechanical ventilation. Both patients had exhibited escalating requirements for sedative drugs while undergoing ventilation yet remained inadequately sedated. The introduction of i.v. methadone in place of i.v. morphine in the sedative regimen rapidly and effectively restored a state of sedation. Hyperalgesia and morphine tolerance appear to be associated; it is proposed that methadone acts primarily, under these circumstances, by re-establishing the analgesic state. Such use of methadone in the morphine-tolerant patient also afforded a concomitant sedative-sparing effect.

Analgesics, Opioid↗
PubMed1975

The possible role of brain histamine and H1 and H2 receptors in the development of morphine tolerance and physical dependence in mice.

The possible role of brain histamine in the mechanisms of morphine tolerance and physical dependence is under investigation in mice. L-histidine and histamine, given during the 'withdrawal' phase, significantly increase tolerance to the analgesic effects of morphine but reduce the degree of physical dependence. Metiamide significantly inhibits tolerance but has no consistent effect on physical dependence. These results suggest that H2 receptors may be involved in the development of morphine tolerance. Mepyramine does not significantly affect tolerance, and with regard to dependence there is an effect only on body weight loss, which is increased. However, combined treatment with metiamide and mepyramine inhibits tolerance significantly more than metiamide alone; and withdrawal jumping is also reduced more significantly by combined treatment than by the separate administration of these drugs. It is suggested that brain histamine is definitely implicated in the mechanisms of the 'withdrawal' phase of morphine tolerance and physical dependence in mice, with H2 receptors probably playing the more important part.

Animals↗
PubMed2002

The effect of cyclosporin A on morphine tolerance and dependence: involvement of L-arginine/nitric oxide pathway.

Cyclosporin A is known to decrease nitric oxide (NO) production in nervous tissues. The effects of systemic cyclosporine A on the induction and expression of morphine tolerance and dependence, acute morphine-induced antinociception, and the probable involvement of the L-arginine/nitric oxide pathway in these effects were assessed in mice. Cyclosporin A (20 mg/kg), N(G)-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) and a combination of the two at lower and per se non-effective doses (5 and 3 mg/kg, respectively) showed a similar pattern of action, inhibiting the induction of tolerance to morphine-induced antinociception and increasing the antinociception threshold in the expression phase of morphine tolerance. These agents also inhibited the expression of morphine dependence as assessed by naloxone-precipitated withdrawal signs, while having no effect on the induction of morphine dependence. L-Arginine, at a per se non-effective dose (60 mg/kg), inhibited the effects of Cyclosporin A. Moreover, acute administration of Cyclosporin A (20 mg/kg) or L-NAME (10 mg/kg) enhanced the antinociception induced by acute administration of morphine (5 mg/kg), while chronic pretreatment with Cyclosporin A (20 mg/kg) or L-NAME (10 mg/kg) for 2 days (twice daily) did not affect morphine-induced antinociception. The inducible nitric oxide synthase inhibitor, aminoguanidine (100 mg/kg), did not alter morphine antinociception, tolerance or dependence. In conclusion, decreasing NO production through constitutive nitric oxide synthase may be a mechanism through which cyclosporin A differentially modulates morphine tolerance, dependence and antinociception.

Analgesics, Opioid↗
PubMed1997

Chronic neurosteroid treatment prevents the development of morphine tolerance and attenuates abstinence behavior in mice.

The effect of neurosteroids on the development of morphine tolerance and dependence was examined in mice. Development of tolerance to the antinociceptive effect of morphine sulfate (10 mg/kg, twice daily for 9 days) was measured in the tail-flick test and dependence was assessed from naloxone (2 mg/kg)-precipitated withdrawal jumps on day 10 of testing. Concomitant chronic administration of neurosteroids, allopregnanolone (0.5 mg/kg), pregnenolone sulfate (2 and 5 mg/kg) or dehydroepiandrosterone sulfate (2 and 5 mg/kg), followed by morphine (10 mg/kg) prevented the development of tolerance to the antinociceptive effect of morphine and suppressed the naloxone-precipitated withdrawal jumps. In contrast, dehydroepiandrosterone acetate (5 mg/kg) failed to modulate the morphine tolerance and dependence. The inhibitory effect was also seen upon concomitant administration of a neurosteroid precursor, progesterone (1-10 mg/kg), and a mitochondrial diazepam binding inhibitor receptor agonist, 4'-chlordiazepam (0.25-1 mg/kg), while an adrenocorticosteroid, hydrocortisone (1 and 10 mg/kg), failed to do so. However, acute treatment with these neurosteroids was not associated with any decrease in withdrawal jumping behavior in morphine-dependent mice. Neurosteroids themselves, at doses employed in the study, did not exert any effects on antinociception. These results support a role for neurosteroids in the development of tolerance to and dependence on morphine and suggest the potential utility of specific neuroactive steroids in its treatment.

Analgesics, Opioid↗
PubMed2004

[Molecular mechanism of morphine tolerance and biological approaches to resolve tolerance].

One of the major problems associated with the chronic use of morphine is tolerance. Repeated uses of morphine to relieve pain often cause patients to develop increasing resistance to the effects of the drugs, so that progressively higher doses are required to achieve the same analgesic effects. Acquired tolerance is thought to be different from dependence or addiction, but molecular mechanism underlying the development of tolerance is still unclear. Tolerance has been explained by desensitization of opioid receptor signaling and loss of functional receptors in the cell surface. The classical hypothesis was that phosphorylation and arrestin binding resulted in uncoupling of the receptor from G proteins, and reduced agonist efficacy. The receptor internalization would then result in fewer functional receptors at the cell surface. These events would cause so-called signaling desensitization. However, recent molecular biological studies have led researchers to revise the classical view of tolerance from observations that morphine does not always promote efficient receptor internalization. Among several key processes, the sequestration and subsequent internalization of the opioid receptor may play an important role for morphine tolerance. In fact, recent studies have suggested that receptor internalization can reduce tolerance. In addition, activation of the NMDA subtype of the glutamate receptor has been suggested as an anti-opioid system in the development of morphine tolerance. In this review, we focus on recent research progress on the morphine tolerance, and molecular biological and clinical approaches to resolve morphine tolerance.

Animals↗
PubMed1991

Selective blockage of delta opioid receptors prevents the development of morphine tolerance and dependence in mice.

Recently, we demonstrated that delta opioid binding sites are involved in the development of morphine tolerance and dependence. In our present work, we studied the effect of the potent and selective delta antagonist, naltrindole (NTI), and its nonequilibrium analog, naltrindole 5'-isothiocyanate (5'-NTII), on the development of morphine tolerance and dependence in mice. In the acute model, mice injected with 100 mg/kg of morphine sulfate s.c. displayed acute tolerance 4 hr later as evidenced by a greater than 3-fold increase of the ED50 of morphine sulfate when compared to that of control mice. The acute tolerance was accompanied by the development of acute physical dependence as seen by the dramatic decrease in the amount of naloxone required to precipitate withdrawal jumping. Likewise, in the chronic model s.c. implantation of morphine pellets (75 mg free base) for 3 days produced tolerance and physical dependence. The ED50 of morphine sulfate in this case was increased by about 19-fold and the amount of naloxone needed to precipitate withdrawal jumping was 40 times lower than that required for acutely dependent mice. The development of acute tolerance and dependence was suppressed markedly in mice pretreated with NTI before induction of tolerance and dependence with 100 mg/kg of morphine sulfate. Multiple administration of either NTI or 5'-NTII before and during implantation with morphine base pellets also inhibited substantially the development of morphine tolerance and dependence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Morphine tolerance and dependence in the nociceptin receptor knockout mice.

Here we report the involvement of nociceptin receptor in tolerance to morphine-induced antinociception and in morphine dependence. There was no different nociceptive perception and antinociceptive effects of morphine between wild-type and the nociceptin receptor knockout mice. Tolerance to morphine (10 mg/kg)-induced antinociception was developed in both wild-type and the nociceptin receptor knockout mice after administration of morphine (10 mg/kg) twice a day for 5 days. When naloxone (5 mg/kg) was administered to mice treated with morphine repeatedly on the 6th day, morphine withdrawal syndrome was observed in both wild-type and the nociceptin receptor knockout mice, which were accompanied by the elevation of cyclic AMP levels. While naloxone benzoylhydrazone (1 mg/kg), a putative antagonist for nociceptin receptor/naloxone benzoylhydrazone-sensitive sites, also induced the morphine withdrawal signs in both wild-type and the nociceptin receptor knockout mice, the jumping signs in the nociceptin receptor knockout mice were less severe than those in wild-type mice. Treatment with naloxone benzoylhydrazone in morphine-dependent wild-type mice caused a significant increase in cyclic AMP levels in the thalamus while it had no effect in the nociceptin receptor knockout mice. The analysis of opioid mu-receptor binding showed no difference between wild-type and the nociceptin receptor knockout mice. These results suggest that the nociceptin receptor/naloxone benzoylhydrazone-sensitive sites contribute to the induction of morphine withdrawal syndrome in part. Furthermore, it is demonstrated that morphine withdrawal syndrome excepting jumping can be induced by naloxone benzoylhydrazone without any changes in the cyclic AMP levels in the thalamus.

Analgesics, Opioid↗
PubMed1997

Enhancement of morphine actions in morphine-naive and morphine-tolerant mice by LY 235959, a competitive antagonist of the NMDA receptor.

1. The effects of LY 235959, a competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, on the analgesic and hypothermic actions of morphine, were determined in nontolerant and morphine-tolerant mice. 2. LY 235959 enhanced the analgesic and hypothermic action of morphine in nontolerant mice. 3. LY 235959 also enhanced the analgesic and hypothermic actions of morphine in morphine-tolerant mice. LY 235959, injected before saline injection, had no effect on the antinociception or the body temperature. 4. It is concluded that competitive antagonism of the NMDA receptor enhances the pharmacologic actions of morphine both in morphine-naive and morphine-tolerant mice and that these actions differ from the noncompetitive antagonism of the NMDA receptors.

Analgesics, Opioid↗
PubMed2004

Increasing of intrathecal CSF excitatory amino acids concentration following morphine challenge in morphine-tolerant rats.

Excitatory amino acids (EAAs) are involved in the development of opioid tolerance. The present study reveals that an increasing of CSF EAAs concentration might be responsible for the losing of morphine's antinociceptive effect in morphine tolerant rats. Male Wistar rats were implanted with two intrathecal (i.t.) catheters and one microdialysis probe, then continuously infused i.t. for 5 days with saline (1 microl/h; control group), morphine (15 micrograms/h), the NMDA antagonist, MK-801 (5 micrograms/h), or morphine (15 micrograms/h) plus MK-801 (5 micrograms/h). Each day, tail-flick responses were measured; in addition, CSF dialysates were collected and CSF amino acids measured by high performance liquid chromatography using a fluorescence detector. Morphine started to lose its analgesic effect on day 2 and this effect was overcome by MK-801. The AD(50) (AD: analgesic dose) was 1.33 micrograms in control animals, 83.83 micrograms in morphine-tolerant rats (a 63-fold shift), and 11.2 micrograms (a 8.4-fold shift) in rats that had received MK-801 plus morphine. No significant differences were observed in CSF amino acid release between the groups from day 1 to day 5. On day 5, after basal dialysate collection, a 10-micrograms challenge of morphine was administered i.t., and CSF samples collected over the next 3 h. After morphine challenge, morphine-tolerant rats showed a significant increase in the release of glutamate and aspartate (131+/-9.5% and 156+/-12% of basal levels, respectively), and no antinociceptive effect in the tail-flick latency test, while MK-801/morphine co-infused rats showed no increase in morphine-induced EAA release and a partial antinociceptive effect (MPE=40%). The present study provides direct evidence for a relationship between EAA release and a lack of an antinociceptive response to morphine, and shows that the NMDA antagonist, MK-801, attenuates both of these effects.

Analgesics, Opioid↗
PubMed2005

Involvement of hypothalamic pituitary adrenal axis on the effects of nifedipine in the development of morphine tolerance in rats.

It has been shown that nifedipine, as a calcium channel blocker, can attenuate the development of tolerance to the antinociceptive effect of morphine; however, the role of HPA axis on this action has not been elucidated. We examined the effect of nifedipine on morphine analgesic tolerance in intact and adrenalectomized (ADX) rats and on HPA activity induced by morphine. Adult male rats were rendered tolerant to morphine by daily injection of morphine (15 mg/kg i.p.) for 8 days. To determine the effect of nifedipine on the development of morphine tolerance, nifedipine (1, 2 and 5 mg/kg i.p.) was injected concomitant with morphine. The tail-flick test was used to assess the nociceptive threshold, before and 30 min after morphine administration in days 1, 3, 5 and 8. Our results showed that despite the demonstration of tolerance in both ADX and sham operated rats, nifedipine in ADX rats prevented morphine tolerance development at a lower dose (2 mg/kg) than in sham operated rats, however corticosterone replacement prevented nifedipine effect in ADX rats. Acute administration of morphine produced significant increase in plasma corticosterone level, and with repeated injection, a tolerance to this neurosecretory effect was developed. Nifedipine (5 mg/kg) attenuated the acute effect of morphine, but could not block its neurosecretory tolerance.

Adrenalectomy↗