Overview of Opioid Tolerance and Physical Dependence

Louie, Alan K.; Way, E. Leong

doi:10.1007/978-3-642-46660-1_26

Cited by 10 publications

(5 citation statements)

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“…1979;Urca et al 1979 Bozarth andWise 1984). Several authors are of the opinion that formation of physical dependence and tolerance is inseparable (see Louie and Way 1991), but many data now indicate that tolerance and dependence are separable processes (Koob and Bloom 1988;Ayesta 1991). Thus Christie et al (1987) have demonstrated tolerance development without producing the abstinence state (characterized by responses to opiate antagonists) in locus coeruleus neurons, and in peripheral organs Schulz (1991) has shown that the vas deferens preparation from mice chronically treated with DADLE shows tolerance to, but no dependence on DADLE (no response to naloxone), while the ileum isolated from guinea pigs receiving fentanyl chronically show both tolerance and dependence (naloxone-induced contractions).…”

Section: Discussionmentioning

confidence: 96%

Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine

et al. 1993

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Nifedipine, 5 mg/kg IP, potentiated the morphine-induced analgesia measured in the hot-plate, but not in the tail-flick test. Further experiments were carried out using the hot-plate test only. Pretreatment with nifedipine partially restores the analgesic action of morphine in morphine-tolerant rats. Co-administration of nifedipine with morphine in a chronic experiment did not prevent the loss of morphine efficiency (an increase in latency of 44% was not significant) and did not prevent the debilitating effect of chronic morphine administration reflected by an inhibition of the body weight gain, but prevented naloxone-induced withdrawal syndrome (quantified by counting head shakes) in the test carried out 24 h after the injection of nifedipine, when the drug did not affect morphine analgesia. Chronic treatment with either morphine or nifedipine did not produce a significant increase in the density of [3H] naloxone or [3H]prazosin binding sites in the cortex and in the rest of the brain (measured 24 h after the last dose), but the combined treatment resulted in a significant increase in the cortical [3H]prazosin binding site density. The present results suggest that opiate tolerance and physical dependence may be separated by co-administration of nifedipine and suggest that the combined chronic treatment with morphine and nifedipine may increase the efficacy of morphine during chronic treatment and prevent development of abstinence.

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Section: Discussionmentioning

confidence: 96%

Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine

et al. 1993

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“…It seems that the induction of these two types of tolerances follow different mechanisms. AMT was not restricted to cellular adaptations of a specific receptor or second messenger cascade like those that influenced NAMT [ 23 ]. AMT is based on integrated associative learning factors and can be justified based on Pavlovian classical conditioning rules [ 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits

et al. 2021

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Background ɣ-aminobutyric acid (GABA) facilitator valproic acid may be able to curb memory disruption induced by morphine exposure. Objective The effects of the GABA facilitator valproic acid on the behavioral tolerance induced by morphine were investigated. Then hippocampal-dependent tasks named spatial-working and short-term memory procedures using the Y-maze apparatus were examined in morphine tolerant rats. Finally, the changes in the expression of hippocampal GABA-A receptors underlying morphine tolerance were also examined. Methods Rats were treated with daily morphine injections, with or without distinct contextual pairing. To examine the effect of valproic acid on morphine tolerance expression, valproic acid was pretreated an hour before morphine. Spatial-working and short-term memory procedures using the Y-maze apparatus were examined in morphine tolerant rats. Afterwards the changes in the expression of hippocampal GABAα receptors using the quantitative real-time PCR and western blot techniques to detect GABArα subunits mRNAs and protein level were studied. Results Our results showed that both learned and non-associative morphine tolerance influence short-term memory and the subjacent expression of GABArα mRNAs and protein level. Despite its attenuating effects on the development and expression of both learned and non-associative morphine tolerance, only associative morphine tolerance-induced memory dysfunction was ameliorated by valproic acid pretreatment. We also found that the expression of GABArα1, α2, α5 subunits mRNAs and GABAα protein level were affected heavier in associative morphine tolerant rats. Conclusion Our data supports the hypothesis that unconditioned and learned morphine tolerance influences short-term memory and the expression of GABArα 1, α2, α5 mRNAs and GABArα protein level differently, and adds to our understanding of the behavioral and molecular aspects of the learned tolerance to morphine effects.

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“…There is no clinically evaluative predictor of uniform opioid resistance, and consequently, the presumption of inefficacy can never be used as the primary justification for the decision to forego a trial of opioid therapy. Durability of response: If tolerance to the analgesic effects of opioid drugs in humans occurred as rapidly and uniformly as tolerance to antinociceptive effects in experimental animal models (96,97), long term opioid therapy would have little clinical utility. Examination of this issue requires an understanding of the mechanisms believed to be involved in the development of tolerance and the fundamental differences between the experimental and clinical settings (98)(99)(100).…”

Section: Therapeutic Efficacymentioning

confidence: 99%

Opioid Therapy for Chronic Nonmalignant Pain

Portenoy

1995

Pain Research and Management

123

145

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RK Portenoy.Opioid therapy for chronic nonmalignant pain. Pain Res Manage 1996;1(1):17-28. Long term administration of an opioid drug for chronic nonmalignant pain continues to be controversial, but is no longer uniformly rejected by pain specialists. This is true despite concerns that the regulatory agencies that oversee physician prescribing of opioid drugs continue to stigmatize the practice. The changing clinical perspective has been driven, in part, by widespread acknowledgement of the remarkably favourable outcomes achieved during opioid treatment of cancer pain. These outcomes contrast starkly with popular teaching about chronic opioid therapy and affirm the potential for prolonged efficacy, tolerable side effects, enhanced function associated with improved comfort and minimal risk of aberrant drug-related behaviours consistent with addiction. A large anecdotal experience in populations with nonmalignant pain suggests that these patients are more heterogeneous and that opioid therapy will greatly benefit some and will contribute to negative outcomes for others. The few controlled clinical trials that have been performed support the safety and efficacy of opioid therapy, but have been too limited to ensure generalization to the clinical setting. A critical review of the medical literature pertaining to chronic pain, opioid pharmacology and addiction medicine can clarify misconceptions about opioid therapy and provide a foundation for patient selection and drug administration. The available data support the view that opioids are no panacea for chronic pain, but should be considered in carefully selected patients using clinically derived guidelines that stress a structured approach and ongoing monitoring of efficacy, adverse effects, functional outcomes and the occurrence of aberrant drug-related behaviours. Key Words: Addiction, Drug dependence, Nonmaligant pain, Opioids, Pain therapyThérapie opioïde pour la douleur chronique non cancéreuse RÉSUMÉ : L'administration à long terme d'un médicament opioïde pour traiter la douleur chronique non cancéreuse reste sujet à controverse mais n'est plus rejetée de façon uniforme par les spécialistes de la douleur. Ceci est vrai même si l'on s'inquiète de ce que les organismes régulateurs qui supervisent la prescription médicale d'agents opioïdes persistent à stigmatiser cette pratique. Le changement de perspective clinique a été motivé en partie par une reconnaissance généralisée des résultats remarquablement favorables obtenus lors du traitement opioïde de la douleur cancéreuse. Ces résultats contrastent carrément avec ce qui est généralement enseigné sur l'administration à long terme d'un médicament opioïde et, confirment un potentiel d'efficacité durable, des effets secondaires supportables, une augmentation de la capacité fonctionnelle associée à une amélioration du bienêtre et, un risque minimal de comportements aberrants liés au médicament compatibles avec une toxicomanie. Une vaste expérience anecdotique chez des populations souffrant d'une douleur non cancéreus...

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Overview of Opioid Tolerance and Physical Dependence

Cited by 10 publications

References 74 publications

Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine

Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine

Unconditioned and learned morphine tolerance influence hippocampal-dependent short-term memory and the subjacent expression of GABA-A receptor alpha subunits

Opioid Therapy for Chronic Nonmalignant Pain

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