Relationship between CYP2B6*6 and cold pressor pain sensitivity in opioid dependent patients on methadone maintenance therapy (MMT)

Zahari Z 1 , Lee CS 2 , Ibrahim MA 3 , Musa N 4 , Mohd Yasin MA 5 , Lee YY 6 Show all authors , Tan SC 4 , Mohamad N 7 , Ismail R 8

Affiliations 

  • 1 Department of Pharmacy, Hospital Universiti Sains Malaysia, Kelantan, Malaysia; Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kelantan, Malaysia. Electronic address: zzalina@usm.my
  • 2 Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia (USM), Kelantan, Malaysia
  • 3 Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kelantan, Malaysia; Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University, Hawler, Iraq
  • 4 Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kelantan, Malaysia
  • 5 Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kelantan, Malaysia; Department of Psychiatry, School of Medical Sciences, Universiti Sains Malaysia (USM), Kelantan, Malaysia
  • 6 School of Medical Sciences, Universiti Sains Malaysia (USM), Kelantan, Malaysia
  • 7 Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kelantan, Malaysia; Faculty of Medicine & Health Sciences, Universiti Sultan Zainal Abidin, Terengganu, Malaysia
  • 8 Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kelantan, Malaysia; Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia
Drug Alcohol Depend, 2016 08 01;165:143-50.
PMID: 27289271 DOI: 10.1016/j.drugalcdep.2016.05.028

Abstract

BACKGROUND: CYP2B6 polymorphisms contribute to inter-individual variations in pharmacokinetics of methadone. Increased pain sensitivity is frequently reported by opioid dependent patients on methadone maintenance therapy (MMT). It is possible, therefore, that genetic polymorphisms in CYP2B6, which affects the metabolism of methadone, influence pain sensitivity among patients on MMT. This study investigated CYP2B6 polymorphisms and pain sensitivity in this group.

METHODS: The cold pressor pain responses of 148 opioid dependent patients receiving MMT were evaluated using the cold pressor test (CPT). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR)-genotyping.

RESULTS: Of the 148 subjects, 77 (52.0%) were carriers of CYP2B6*6 allele. CYP2B6*6 allele carriers had shorter cold pain threshold and pain tolerance times than non-carriers of CYP2B6*6 allele (21.05s vs 33.69s, p=0.036 and 27.15s vs 44.51s, p=0.020, respectively). Pain intensity scores of the CYP2B6*6 allele carriers was 67.55, whereas that of the CYP2B6*6 allele non-carriers was 64.86 (p=0.352).

CONCLUSION: Our study indicates that the CYP2B6*6 allele is associated with a lower pain threshold and lower pain tolerance among males with opioid dependence on MMT. The CYP2B6*6 allele may provide a mechanistic explanation for clinical observations of heightened pain sensitivity among opioid dependent patients receiving MMT.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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