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



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.



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).



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.
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.
Zalina
Z
Zahari
Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia (USM), Kelantan, Malaysia.
Chee Siong
CS
Lee
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.
Muslih Abdulkarim
MA
Ibrahim
Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kelantan, Malaysia.
Nurfadhlina
N
Musa
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.
Mohd Azhar
MA
Mohd Yasin
School of Medical Sciences, Universiti Sains Malaysia (USM), Kelantan, Malaysia.
Yeong Yeh
YY
Lee
Pharmacogenetics and Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia (USM), Kelantan, Malaysia.
Soo Choon
SC
Tan
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.
Nasir
N
Mohamad
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.
Rusli
R
Ismail
D000328:Adult; D000483:Alleles; D000701:Analgesics, Opioid / Q000627:therapeutic use; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008691:Methadone / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy / Q000235:genetics*; D017288:Pain Threshold / Q000187:drug effects*; D011110:Polymorphism, Genetic
D000701:Analgesics, Opioid; D065702:Cytochrome P-450 CYP2B6; D008691:Methadone
CYP2B6; CYP2B6*6; Cold pressor test (CPT); Male patients; Methadone maintenance therapy (MMT); Opioid dependence; Pain sensitivity