1. 2019;22;97-107OPRM1 Gene Interaction with Sleep in Chronic Pain Patients Treated with Opioids
   Observational Study
   Cesar Margarit, MD, PhD, Purificacion Ballester, LMS, Maria-del-Mar Inda, PhD, Reyes Roca, LMS, Luis Gomez, LMS, Beatriz Planelles, LMS, Raquel Ajo, LMS, Domingo Morales, PhD, and Ana M. Peiro, MD, PhD.

BACKGROUND: The experience of chronic non-cancer pain (CNCP) is one of the most common reasons individuals seek medical attention. Patients with CNCP frequently experience concomitant sleep-related problems.

OBJECTIVES: The aim was to evaluate sleep problems in opioid naïve CNCP patients, before and 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 assessed at baseline and 3 months after opioid titration in 231 opioid naïve CNCP patients. Sleep data was compared with a matched-control group (n = 64). Morphine equivalent daily doses, adverse events, and drugs prescribed for pain were also registered. OPRM1 polymorphism rs1799971 was analyzed by RT-PCR. Ethics Committee approved the study and results were analyzed 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 increased quality 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 sleep problems.

LIMITATIONS: Total number of subjects studied was relatively small and most patients were on other non-opioid centrally-acting medications.

CONCLUSIONS: Opioids decreased CNCP severity, improving patients’ psychological areas, and quality of life. However, patients with OPRM1 118-GG genotype indicated an increase in sleep problems and worsening sleep pattern while taking opioids.

KEY WORDS: OPRM1, pharmacogenetics, MOS-Sleep, opioids, chronic noncancer pain, sleep related problems, sleep problem index SLP-6 and SLP-9