title: 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: 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.
authors: Department of Surgical Sciences, University Hospital, Uppsala, SE 75185, Sweden.
authors: Annica
authors: A
authors: Rhodin
authors: Alfhild
authors: A
authors: Grönbladh
authors: Harumi
authors: H
authors: Ginya
authors: Kent W
authors: KW
authors: Nilsson
authors: Andreas
authors: A
authors: Rosenblad
authors: Qin
authors: Q
authors: Zhou
authors: Mats
authors: M
authors: Enlund
authors: Mathias
authors: M
authors: Hallberg
authors: Torsten
authors: T
authors: Gordh
authors: Fred
authors: F
authors: Nyberg
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D015220:Calcium Channels / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011788:Quality of Life; D017450:Receptors, Opioid, mu / Q000235:genetics*; D001615:beta-Endorphin / Q000097:blood*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; C425903:CACNA2D1 protein, human; D015220:Calcium Channels; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D001615:beta-Endorphin
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