OPRM1 Gene Interaction with Sleep in Chronic Pain Patients Treated with Opioids

Background: The experience of chronic non-cancer pain (CNCP) is one of the mostcommon reasons individuals seek medical attention. Patients with CNCP frequently experienceconcomitant sleep-related problems.Objectives: The aim was to evaluate sleep problems in opioid naïve CNCP patients, beforeand after opioid titration, analyzing the influence of OPRM1 gene variants.Study Design: A prospective, cohort, observational study.Setting: This study was performed at the Pain Unit of the Alicante University General Hospital.Methods: Pain and Medical Outcomes Study Sleep questionnaire (MOS-Sleep) were assessedat baseline and 3 months after opioid titration in 231 opioid naïve CNCP patients. Sleepdata was compared with a matched-control group (n = 64). Morphine equivalent daily doses,adverse events, and drugs prescribed for pain were also registered. OPRM1 polymorphismrs1799971 was analyzed by RT-PCR. Ethics Committee approved the study and results wereanalyzed by R software.Results: After 3 months of opioid titration, patients with CNCP (63 ± 14 years, 64% female,VAS 74 ± 17 mm) significantly decreased pain intensity, anxiety and depression, and increasedquality of life. Sleep problems were significantly more frequent in females (P = 0.002). Age,quality of life, anxiety, and depression all influenced sleep disturbances and problems indices,which were significantly different from the control group. Furthermore, the OPRM1 118-GG genotype was also associated with significantly lower sleep adequacy, and more sleepproblems.Limitations: Total number of subjects studied was relatively small and most patients were onother non-opioid centrally-acting medications.Conclusions: Opioids decreased CNCP severity, improving patients’ psychological areas, andquality of life. However, patients with OPRM1 118-GG genotype indicated an increase in sleepproblems and worsening sleep pattern while taking opioids.Key words: OPRM1, pharmacogenetics, MOS-Sleep, opioids, chronic noncancer pain, sleeprelated problems, sleep problem index SLP-6 and SLP-9