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

Abstract

BackgroundOpioids 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.ResultsThe 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.ConclusionsAlthough 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.

The effect of laserpuncture at the LI4 Hegu point on the plasma levels of β-endorphin in healthy subjects

“…In addition, variations in the Na+, K+, and Ca2+ ion channels can provide different β-endorphin responses. The present study concluded that β-endorphin levels in the blood circulation are influenced by genetic and sex factors [35]. Rhodin et al's hypothesis supports the variations in results that occurred in this study.…”

“…There are several conditions that may lead to a decrease in β-endorphin levels: excess physical exercise [30], depression [31], use of prednisone and steroids [32], irritable bowel syndrome [33], menstrual cycle [26], alcoholic addiction [34], and genetics [35]. Rhodin et al, in a study comparing the analysis of β-endorphins with genetic polymorphism, suggested there may be differences in men and women due to genetic variation.…”

Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical Practice

“…An increased risk for morphine-induced nausea and vomiting was reported in whites with the 3435TT genotype undergoing colorectal surgery (32 ). A higher frequency of opioid-related adverse events such as sweating and sedation was reported in 3435TT genotyped individuals receiving remifentanil for spinal fusion surgery (33 ). Other SNPs in ABCB1, 1236CϾT (rs1128503) and 2677GϾT/A (rs2032582), have also been found to be related to adverse events (26,32,34,35 ).…”

Association of Single-Nucleotide Polymorhism C3435T in the ABCB1 Gene with Opioid Sensitivity in Treatment of Postoperative Pain

“…The most common polymorphisms found in ABCB1 are 1236C > T, 2677 G > T/A/C, and 3435C > T. It has been suggested that the genetic variations in ABCB1 could be a cause of inter-individual differences in drug response [9]. In this study we investigated the C3435T Single Nucleotide Polymorphisms -SNPs of ABCB1 where C > T. Thus, the major allele is CC, the heterozygous minor allele is CT and homozygous minor allele is TT.…”