Analgesia and central side‐effects: two separate dimensions of morphine response

Droney, Joanne; Gretton, Sophy; Sato, Hajime; Ross, Joy; Branford, Ruth; Welsh, Kenneth I.; Cookson, William; Riley, Julia

doi:10.1111/bcp.12008

Cited by 35 publications

(27 citation statements)

References 64 publications

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“…A similar lack of association was observed between A118G and nausea or vomiting due to fentanyl treatment in an additional study [33]. The intronic SNP rs2075572 was also only nominally associated with central side effects of morphine, such as nausea, drowsiness, and hallucinations [46]. In contrast to these negative findings, two independent studies observed decreased pruritus in women carrying the G allele of A118G after morphine treatment for post-caesarean section pain [38, 47].…”

Section: The μ-Opioid Receptormentioning

confidence: 65%

Pharmacogenetics of OPRM1

Crist

Berrettini

2014

Pharmacology Biochemistry and Behavior

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Pharmacogenetic research has the potential to explain the variation in treatment efficacy within patient populations. Understanding the interaction between genetic variation and medications may provide a method for matching patients to the most effective therapeutic options and improving overall patient outcomes. The OPRM1 gene has been a target of interest in a large number of pharmacogenetic studies due to its genetic and structural variation, as well as the role of opioid receptors in a variety of disorders. The mu-opioid receptor (MOR), encoded by OPRM1, naturally regulates the analgesic response to pain and also controls the rewarding effects of many drugs of abuse, including opioids, nicotine, and alcohol. Genetic variants in OPRM1, particularly the nonsynonymous polymorphism A118G, have been repeatedly associated with the efficacy of treatments for pain and various types of dependence. This review focuses on the current understanding of the pharmacogenetic impact of OPMR1, primarily in regards to the treatment of pain and addiction.

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Section: The μ-Opioid Receptormentioning

confidence: 65%

Pharmacogenetics of OPRM1

Crist

Berrettini

2014

Pharmacology Biochemistry and Behavior

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“…In this study OPRK rs7824175 was associated with variability in mechanical muscle pain. We have previously identified an association between OPRK rs7824175 and residual pain in a cohort of cancer patients titrated on oral morphine [25]. …”

Section: Discussionmentioning

confidence: 99%

“…Five polymorphisms in OPRM (rs6912029G/T, rs179997A/G, rs56364C/T, rs9479757G/A, rs533586C/T) , eight in OPRK (rs1050415T/C, rs7836120A/G, rs647379T/C, rs1365098G/T, rs701677T/A, rs7824175G/C, rs16918875C/T, rs963549G/A) and five in OPRD (rs1042114G/T, rs533123G/A, rs419335A/G, rs2236857T/C, rs2234918C/T) were included in the study. The details of primers are as previously described [25]. Within each of the genes polymorphisms were selected to try to cover allelic diversity across each gene.…”

Section: Methodsmentioning

confidence: 99%

Gender, Variation in Opioid Receptor Genes and Sensitivity to Experimental Pain

et al. 2013

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BackgroundPain tolerance is subject to considerable inter-individual variation, which may be influenced by a number of genetic and non-genetic factors. The mu, delta and kappa opioid receptors play a role in pain perception and are thought to mediate different pain modalities. The aim of this study was to explore associations between pain thresholds and gender and genetic variants in the three opioid receptor genes (OPRM, OPRD and OPRK). Experimental multi-modal pain data from previously published studies carried out in healthy Caucasian volunteers were used in order to limit the number of confounders to the study outcome. Data on thermal skin pain (n=36), muscle pressure pain (n=31) and mechanical visceral pain (n=50)) tolerance thresholds were included.ResultsNineteen genetic polymorphisms were included in linear regression modeling. Males were found to tolerate higher thermal and muscle pressure pain than females (p=0.003 and 0.02). Thirty four percent of variability in thermal skin pain was accounted for by a model consisting of OPRK rs6473799 and gender. This finding was just outside significance when correction for multiple testing was applied. Variability in muscle pressure pain tolerance was associated with OPRK rs7016778 and rs7824175. These SNPs accounted for 43% of variability in muscle pressure pain sensitivity and these findings remained significant after adjustment for multiple testing. No association was found with mechanical visceral pain.ConclusionThis is a preliminary and hypothesis generating study due to the relatively small study size. However, significant association between the opioid receptor genes and experimental pain sensitivity supports the influence of genetic variability in pain perception. These findings may be used to generate hypotheses for testing in larger clinical trials of patients with painful conditions.

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“…Six polymorphisms in OPRM1 ( rs6912029G/T , rs1799971A/G ( A118G ), rs589046 C/T , rs563649 C/T , rs9479757G/A and rs533586C/T ), eight in OPRK1 ( rs10504151T/C , rs7836120A/G , rs6473799T/C , rs1365098G/T , rs7016778T/A , rs7824175G/C , rs16918875C/T and rs963549G/A ) and five in OPRD1 ( rs1042114G/T , rs533123G/A , rs419335A/G , rs2236857T/C and rs2234918C/T ) were included in the study. The details of the primers have been published elsewhere .…”

Section: Methodsmentioning

confidence: 99%

The genetic influences on oxycodone response characteristics in human experimental pain

Olesen

Sato

Nielsen

et al. 2015

Fundamemntal Clinical Pharma

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Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P < 0.0001) and rs563649 (P < 0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P = 0.015), rs1799971 (P = 0.045), rs9479757 (P = 0.009) and rs533586 (P = 0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold, however, one OPRD1 rs419335 reached significance (P = 0.015). Another OPRD1 SNP rs2234918 (P = 0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone.

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Analgesia and central side‐effects: two separate dimensions of morphine response

Cited by 35 publications

References 64 publications

Pharmacogenetics of OPRM1

Pharmacogenetics of OPRM1

Gender, Variation in Opioid Receptor Genes and Sensitivity to Experimental Pain

The genetic influences on oxycodone response characteristics in human experimental pain

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