Splice variation of the mu-opioid receptor and its effect on the action of opioids

Gretton, Sophy; Droney, Joanne

doi:10.1177/2049463714547115

Cited by 11 publications

(10 citation statements)

References 52 publications

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“…MORs are encoded by a single structural gene (Opioid receptor mu 1, Oprm1 ) consisting of 4 exons. Exon 1 codes for the extracellular N‐terminal and first transmembrane domain, exons 2 and 3 for the remaining transmembrane domains and exon 4 for amino acids of the C‐terminal region . We analyzed Oprm1 mRNA levels by using RT‐SYBR green quantitative PCR assay.…”

Section: Resultsmentioning

confidence: 99%

“…Our results show that the elevated MOR mRNA expression corresponds to the increase in protein levels and for the enhancement of the functional response to MOR activation. The Oprm1 gene undergoes extensive splice variants, and several of these are functionally relevant . We focused on the MOR‐1S and MOR‐1T splice variants, which are the most abundantly expressed in the striatum.…”

Section: Discussionmentioning

confidence: 99%

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Enhanced mu opioid receptor–dependent opioidergic modulation of striatal cholinergic transmission in DYT1 dystonia

et al. 2017

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Mice with the DYT1 dystonia mutation exhibit an enhanced response to mu receptor activation, dependent on selective receptor gene upregulation. Our data suggest a novel role for striatal opioid signaling in motor control, and more important, identify mu opioid receptors as potential targets for pharmacological intervention in dystonia. © 2017 International Parkinson and Movement Disorder Society.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Enhanced mu opioid receptor–dependent opioidergic modulation of striatal cholinergic transmission in DYT1 dystonia

et al. 2017

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“…There is a growing appreciation that individuals may responded differently to opioids due to variants of the opioid receptor. The opioid receptor mu has several polymorphisms and variants, which may be associated with differences in morphine‐induced cell signals …”

Section: Discussionmentioning

confidence: 99%

“…The opioid receptor mu has several polymorphisms and variants, which may be associated with differences in morphine-induced cell signals. [89][90][91] Dever et al 92 showed that MOR variants may be differently regulated in patients with HIV who have varying levels of neurocognitive impairment. Hypothetically, therefore, when exploring the effects of opioids on cognition, the influence of genetic and molecular factors should also be considered as contributing to individual responses.…”

Section: Pain Opioids and Cognitionmentioning

confidence: 99%

Systematic Review and Meta‐Analysis on Neuropsychological Effects of Long‐Term Use of Opioids in Patients With Chronic Noncancer Pain

et al. 2018

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Background and Objective Opioid treatments are often prolonged because of the pathology causing pain. We focused on the cognitive functions in patients with chronic pain treated with opioids. This topic is currently controversial, but in practice, the consequences are important in patients’ daily lives, social interactions, working ability, and driving. Database and Data Treatment Medline and Embase databases were searched for eligible articles. We included studies that enrolled patients with chronic noncancer pain, studies with patients receiving opioid treatment, studies with a control group not using opioids, and studies in which cognitive functions were evaluated with specific tests. The cognitive areas examined were as follows: attention, reaction time, executive functions, psychomotor speed, memory, and working memory. From 356 abstracts screened, 9 articles satisfied eligibility criteria and were included in our review: 7 observational and 7 experimental studies. We classified the pain treatments as follows: opioids, other drugs active on the central nervous system (CNS) (antidepressants/anticonvulsants), and treatments not specifically targeted to the CNS. Results Statistically significant differences were seen only with regard to attention between opioids alone and no centrally acting treatment (standardized mean difference [SMD]: −0.53, 95% confidence interval [CI] : −0.91, −0.15; P = 0.007; I2 = 23%) and between opioids combined with antidepressants and/or anticonvulsants and no centrally acting treatment (SMD: −0.62, 95% CI: −1.04, −0.20; P = 0.004; I2 = 0%). No other significant differences were observed. Conclusions Opioids reduce attention when compared with treatments not targeted on the CNS. If opioids are used together with antidepressants and/or anticonvulsants, this effect increases. Significance These findings on the neuropsychological effects of opioids could be used to generate strategies to refine pain treatments.

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“…It is hypothesized that compounds promoting G signaling will produce analgesia while avoiding the β-arrestin complex-dependent effects leads to less respiratory depression [106]. The presence of several OPRM1 splice variants leads to a different efficacy of each opioid receptor [107], where each splice variant may exhibit a distinct pharmacological profile explaining the different opioid consumptions between individuals [108]. μopioid receptor heterodimerization further diversifies the possible opioid response since dimerization will affect intracellular pathways [109,110].…”

Section: Pharmacodynamic Factors Affected By Polymorphisms μ-Opioid Rmentioning

confidence: 99%

Are Opioids Effective in Relieving Neuropathic Pain?

Schembri

2018

SN Compr. Clin. Med.

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Neuropathic pain (NP) and its treatment are considered to constitute an unmet need, with a high-multidimensional impact on society and the sufferer. The broad spectrum of opioid analgesics is considered beneficial for acute pain, yet these drugs pose serious controversial issues due to the potential for adverse behavior and a higher chance of tolerance and addiction in long-term use. Opioids like other first-line medications for NP, will not be useful for every patient suffering from chronic NP. However, due to their possible adverse effects, opioids are considered as second-or third-line medications by various guidelines. Therefore, this literature review was conducted to evaluate the status of opioids in NP and to asses if any recent research has shed further evidence on their efficacy or the contrary. The literature reviewed showed that the mechanisms underlying NP, may themselves contribute to the reduced effect of opioids in this condition. Also, various genetic polymorphisms affecting pharmacokinetic and pharmacodynamic factors are discussed, providing further evidence for the variability in opioid response. Although opioids may reduce NP, nociceptive pain tends to be more responsive to opioids compared to NP. Also, opioids seem to be more effective in intermediate term studies of up to 12 weeks and being mostly effective in peripheral NP compared to supraspinal NP and being least effective in central NP. However, there is still no robust evidence that any specific opioid agent is better than any other one for NP, but it is possible that opioids targeting multiple mechanisms may provide benefit. A limitation of many trials is the lack of consideration for the comorbid psychological aspects of NP, which tend to lower opioid analgesia.

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Splice variation of the mu-opioid receptor and its effect on the action of opioids

Cited by 11 publications

References 52 publications

Enhanced mu opioid receptor–dependent opioidergic modulation of striatal cholinergic transmission in DYT1 dystonia

Enhanced mu opioid receptor–dependent opioidergic modulation of striatal cholinergic transmission in DYT1 dystonia

Systematic Review and Meta‐Analysis on Neuropsychological Effects of Long‐Term Use of Opioids in Patients With Chronic Noncancer Pain

Are Opioids Effective in Relieving Neuropathic Pain?

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