Combined analysis of circulating β-endorphin with gene polymorphisms in OPRM1, CACNAD2 and ABCB1 reveals correlation with pain, opioid sensitivity and opioid-related side effects.
paper
Cited
Public
- Authors
- Rhodin, Annica; Grönbladh, Alfhild; Ginya, Harumi; Nilsson, Kent W; Rosenblad, Andreas; Zhou, Qin; Enlund, Mats; Hallberg, Mathias; Gordh, Torsten; Nyberg, Fred
- Year
- 2013
- Journal
- Molecular brain
- PMID
- 23402298
- DOI
- 10.1186/1756-6606-6-8
- PMCID
- PMC3602034
BACKGROUND: Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the μ-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide β-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls. RESULTS: The plasma β-endorphin levels were significantly higher in controls than in pain patients.A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found. CONCLUSIONS: Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids.
Genotype frequency of ABCB1. The genotype frequency of the ABCB1 SNP in chronic pain with different opioid sensitivity. For further details see Methods and Results.
β-endorphin levels and the ABCB1 SNP. Plasma levels of the opioid peptide β-endorphin in males and females with different alleles of the ABCB1 SNP. A tendency towards sex difference (p = 0.057) in the group carrying the minor TT allele is indicated. For further details see Methods and Results. Values are presented as mean ± SEM.
Scores of pain and other symptoms. Scores of pain and other symptoms for patients carrying the various ABCB1 alleles. For further details see Methods and Results.
Quality of Life and symptom scores. Quality of Life (QoL) and symptom scores in patients carrying the various alleles of the ABCB1 gene. For further details see Methods and Results.
The genotype frequency of CACNA2D2. The genotype frequency of the CACNA2D2 gene in chronic pain patients with different opioid sensitivity. For further details see Methods and Results.
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| Name | Type |
|---|---|
| 0.1xSSC local | drug |
| 1236C>T local | variant |
| 1xSSC local | drug |
| 2677G>T/A/C local | variant |
| 2xSSC local | drug |
| 3435C>T local | variant |
| A118G SNP | variant |
| ABCB1 local | gene |
| ABCB1 3435C>T local | variant |
| ABCB1 CC allele local | variant |
| ABCB1 rs1045642 local | variant |
| ABCB1 TT allele local | variant |
| ABCB1 variant local | variant |
| Abdominal hysterectomy local | cohort |
| AccuPrime Taq DNA polymerase local | drug |
| adverse effects | phenotype |
| Analgesic requirements local | phenotype |
| analgesic response | phenotype |
| anterior lobe of the pituitary gland local | anatomy |
| anti-β-endorphin antiserum local | drug |
| blood-brain barrier | anatomy |
| brain tissue | anatomy |
| CACNA2D local | gene |
| CACNA2D2 | gene |
| CACNA2D2 G>A allele local | variant |
| CACNA2D2 G>A SNP local | variant |
| CACNA2D2 major allele local | variant |
| CACNA2D2 rs5030977 local | variant |
| CACNA2D variant local | variant |
| calcium channel | drug |
| Calcium channel fragment gene local | gene |
| Cancer pain local | phenotype |
| Caucasian population | cohort |
| CC allele local | variant |
| chronic low back pain local | phenotype |
| chronic low-back pain local | phenotype |
| Chronic low back pain local | phenotype |
| chronic low-back pain patients local | cohort |
| chronic pain | phenotype |
| chronic pain disorders local | phenotype |
| Clinical chronic pain cohort local | cohort |
| control group | cohort |
| control groups | cohort |
| control population | cohort |
| controls | cohort |
| control subjects | cohort |
| CT allele local | variant |
| Cy5 probe local | drug |
| Cy5-Tag1 local | drug |
| Degenerative disc disease local | phenotype |
| delta receptor local | drug |
| DNA | drug |
| drug response | phenotype |
| Dry mouth local | phenotype |
| early respiratory depression local | phenotype |
| EDTA | drug |
| emotional function local | phenotype |
| EURIA-β-Endorphin kit local | drug |
| EURO-DIAGNOSTICA AB local | cohort |
| fentanyl | drug |
| formic acid | drug |
| frozen plasma local | drug |
| gabapentin | drug |
| G allele | variant |
| Hardy-Weinberg equilibrium local | phenotype |
| healthy controls | cohort |
| Heroin dose local | phenotype |
| higher pressure pain threshold local | phenotype |
| high opioid sensitivity local | phenotype |
| high responder local | cohort |
| high responder | phenotype |
| high responders local | cohort |
| High responders local | cohort |
| High responders local | phenotype |
| high responders to remifentanil local | cohort |
| high responder to remifentanil local | phenotype |
| HotGoldStar DNA polymerase local | drug |
| human serum albumin local | drug |
| Invitrogen | drug |
| Low back pain patients local | cohort |
| Lumbar fusion surgery local | phenotype |
| Magtration 12GC system local | drug |
| major allele CC local | variant |
| male patients | cohort |
| Malignant disease local | phenotype |
| men | cohort |
| Men with chronic pain local | cohort |
| Methadone | drug |
| migraine | phenotype |
| minor allele TT local | variant |
| MOP receptor local | drug |
| morphine | drug |
| muscular tension local | phenotype |
| Muscular tension local | phenotype |
| mutant mice | cohort |
| Nanodrop | drug |
| nausea | phenotype |
| neuropathic pain | phenotype |
| nociception | phenotype |
| non-responder local | cohort |
| non-responder local | phenotype |
| non-responders local | cohort |
| Non-responders local | cohort |
| Non-responders | phenotype |
| normal responder local | cohort |
| normal responder local | phenotype |
| normal responders local | cohort |
| Normal responders local | cohort |
| Normal responders local | phenotype |
| Obstipation local | phenotype |
| opioid | drug |
| opioid dependence | phenotype |
| opioid-induced hyperalgesia | phenotype |
| opioid-related side effects local | phenotype |
| Opioid-related symptoms local | phenotype |
| opioid requirements local | phenotype |
| opioid responders local | cohort |
| Opioid responders local | cohort |
| opioid sensitivity | phenotype |
| opioid side effects local | phenotype |
| Opioid side effects local | phenotype |
| Opioid Side Effects local | phenotype |
| Opioid toxicity local | phenotype |
| OPMR1 local | gene |
| OPMR1 A>G local | variant |
| OPRM1 | cohort |
| OPRM1 118 G variant local | variant |
| OPRM1 A118G | cohort |
| OPRM1 A118G polymorphism local | variant |
| OPRM1 A118G (rs1799971) local | variant |
| OPRM1 IVS2+31 G>A local | variant |
| OPRM1 major allele local | variant |
| OPRM1 minor allele local | variant |
| OPRM1 variant local | variant |
| pain | phenotype |
| Pain levels local | phenotype |
| pain perception | phenotype |
| pain processing pathways local | phenotype |
| Pain relieving drugs local | drug |
| pain sensitivity | phenotype |
| patients | cohort |
| patients with chronic low back pain local | cohort |
| patients with chronic pain local | cohort |
| PCR Clean-Up Kit local | drug |
| PCR product | drug |
| perceived stress | phenotype |
| P-glycoprotein local | drug |
| Pharmacodynamics of opioids local | phenotype |
| Pharmacokinetics of opioids local | phenotype |
| phosphate local | drug |
| Pomc | gene |
| population | cohort |
| postoperative pain local | phenotype |
| Postoperative pain local | phenotype |
| pregabalin local | drug |
| pressure pain threshold | phenotype |
| pruritus | phenotype |
| pyridine | drug |
| quality of life | phenotype |
| quetiapine local | drug |
| remifentanil local | drug |
| Remifentanil local | drug |
| remifentanil response local | phenotype |
| R-methadone local | drug |
| salmon sperm DNA local | drug |
| SDS | drug |
| sedatives | drug |
| sex | phenotype |
| sodium azide | drug |
| SP-Sephadex C-25 gel local | drug |
| stress | phenotype |
| sweating | phenotype |
| symptoms | phenotype |
| TaKaRa LA Taq local | drug |
| TaKaRa LA Taq polymerase local | drug |
| tension local | phenotype |
| Total knee arthroplasty local | cohort |
| Trasylol local | drug |
| TT allele local | variant |
| voltage-gated calcium channels local | gene |
| women | cohort |
| women in labor local | cohort |
| β-endorphin | drug |
| β-mercaptoethanol | drug |
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External
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| The Role of Clinical Pharmacogenetics and Opioid Interactions in Pain Management: Current Evidence and Future Perspectives. | Di Salvo C et al. | — | 2026 | → |
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