Differential development of acute tolerance to analgesia, respiratory depression, gastrointestinal transit and hormone release in a morphine infusion model

Ling, Geoffrey; Paúl, Dennis; Simantov, Ronit; Pasternak, Gavril W.

doi:10.1016/0024-3205(89)90272-5

Cited by 115 publications

(71 citation statements)

References 24 publications

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“…A number of studies have suggested that opiate control of respiration might be due to activation of a different subset of ORs ( 2 OR, type 2 OR) as opposed to those that are believed to mediate antinociception ( 1 OR, type 1 OR) (Ling et al, 1985(Ling et al, , 1989. Others have also noted this difference, finding less correlation between antinociception and respiratory suppression with highly selective OR agonists (Pick et al, 1991;Stott and Pleuvry, 1991).…”

Section: Morphine Side Effects In ␤-Arrestin 2 Knockout Mice 1199mentioning

confidence: 99%

Morphine Side Effects in β-Arrestin 2 Knockout Mice

Raehal¹,

Walker²,

Bohn³

2005

J Pharmacol Exp Ther

542

496

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Morphine is a potent analgesic, yet, like most opioid narcotics, it exerts unwanted side effects such as constipation and respiratory suppression, thereby limiting its clinical utility. Pharmacological approaches taken to preserve the analgesic properties, while eliminating the unwanted side effects, have met with very limited success. Here, we provide evidence that altering opioid receptor regulation may provide a novel approach to discriminate morphine's beneficial and deleterious effects in vivo. We have previously reported that mice lacking the G protein-coupled receptor regulatory protein, ␤-arrestin 2, display profoundly altered morphine responses. ␤-Arrestin 2 knockout mice have enhanced and prolonged morphine analgesia with very little morphine tolerance. In this report, we examine whether the side effects of morphine treatment are also augmented in this animal model. Surprisingly, the genetic disruption of opioid receptor regulation, while enhancing and prolonging analgesia, dramatically attenuates the respiratory suppression and acute constipation caused by morphine.

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Section: Morphine Side Effects In ␤-Arrestin 2 Knockout Mice 1199mentioning

confidence: 99%

Morphine Side Effects in β-Arrestin 2 Knockout Mice

Raehal¹,

Walker²,

Bohn³

2005

J Pharmacol Exp Ther

542

496

View full text Add to dashboard Cite

show abstract

“…This lack of tolerance differs from other adverse effects of opioid analgesics and could possibly be related to the actions associated with μ-opioid receptor subtypes (eg, tolerance develops for activities that are μ-1 dependent versus other subtypes). [26][27][28] Given the lack of tolerance development to OIC, it is important that OIC be anticipated and be treated as appropriate in patients receiving opioid analgesics. 4 The strength of this placebo crossover analysis is that the design allowed patients to serve as their own controls when comparing the efficacy and safety of methylnaltrexone versus placebo.…”

Section: Discussionmentioning

confidence: 99%

(451) Efficacy and safety of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain: a placebo crossover analysis

Viscusi¹,

Barrett²,

Paterson³

et al. 2014

The Journal of Pain

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“…Tolerance to the reward effect occurs quickly, whereas tolerance to respiratory depression occurs much more slowly. 17 This mismatch in tolerance of effect may lead to increase in opioid doses to maintain analgesia or euphoria, and also places patients at a higher risk of overdose. 18 …”

Section: Definitionsmentioning

confidence: 99%

Acute Pain Management in Hospitalized Adult Patients with Opioid Dependence: A Narrative Review and Guide for Clinicians

Raub

Vettese

2017

Journal of Hospital Medicine

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Pain management is a core competency of hospital medicine, and effective acute pain management should be a goal for all hospital medicine providers. The prevalence of opioid use in the United States, both therapeutic and non-medical in origin, has dramatically increased over the past decade. Although nonopioid medications and nondrug treatments are essential components of managing all acute pain, opioids continue to be the mainstay of treatment for severe acute pain in both opioid-naïve and opioid-dependent patients. In this review, we provide an evidence-based approach to appropriate and safe use of opioid analgesics in treating acute pain in hospitalized patients who are opioid-dependent.

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Differential development of acute tolerance to analgesia, respiratory depression, gastrointestinal transit and hormone release in a morphine infusion model

Cited by 115 publications

References 24 publications

Morphine Side Effects in β-Arrestin 2 Knockout Mice

Morphine Side Effects in β-Arrestin 2 Knockout Mice

(451) Efficacy and safety of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain: a placebo crossover analysis

Acute Pain Management in Hospitalized Adult Patients with Opioid Dependence: A Narrative Review and Guide for Clinicians

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