PMID- 32149782
OWN - NLM
STAT- MEDLINE
DCOM- 20210818
LR  - 20210818
IS  - 1536-5409 (Electronic)
IS  - 0749-8047 (Linking)
VI  - 36
IP  - 6
DP  - 2020 Jun
TI  - Sex Bias and Genotype Influence on Opioid Safety Profile in Chronic Low Back 
      Pain.
PG  - 420-429
LID - 10.1097/AJP.0000000000000824 [doi]
AB  - OBJECTIVES: The use of opioids to relieve pain is a challenge because of the high 
      variability in dose requirements and tolerance profiles. Among potential 
      modulators are the individual's genetic background and being female. Our aim was 
      to evaluate sex bias and genotype-related influence on opioid titration safety, 
      in chronic low back pain (CLBP), the most frequent chronic noncancer pain. 
      METHODS: A 3-year prospective study was developed in opioid-naive CLBP patients. 
      Data were self-reported by patients (pain [Visual Analogy Scale], adverse events 
      [AEs], and health care resource utilization) and physicians (analgesic 
      prescription, morphine equivalent daily dose, and suspected adverse drug 
      reactions [ADRs]). Outcomes were analyzed as patients with AEs (case) or without 
      (control) together with patients' sex and genotype. Gene variants in OPRM1 
      (rs1799971), COMT (rs4680), ABCB1 (rs1045642), UGT2B7 (rs12233719 and rs7438135), 
      KCNJ6 (rs2070995 and rs6517442), and CYP3A5*3 (rs776746) were assessed. The 
      hospital ethics committee approved the study, and statistical analyses were 
      performed with R, v.3.2.4. RESULTS: A total of 179 patients were included (64% 
      female, mean pain intensity 73+/-16 mm), and 90% of them presented at least 1 AE 
      (median of 3 (1 to 6) AEs/patient) with a rate of 5 AEs: 1 ADR without 
      differences due to sex. However, there is a significant delay in referral of 
      female patients (a mean of 6 years) to the Pain Unit, being significantly 3 to 5 
      times more likely to present sleep or psychiatric disorders. Meanwhile male 
      individuals showed more sexual and reproductive system disorders. Genotypes 
      influenced skin (COMT, G472A-GG) and gastrointestinal (ABCB1, C3435T-CC) related 
      problems. CONCLUSIONS: Sex bias affects female patients resulting in a CLBP 
      diagnostic delay and a different analgesic safety profile. Moreover, the 
      individual's genetic background might be useful to predict certain AEs in 
      opioid-naive patients under an opioid titration procedure. Addressing sex in 
      necessary to resolve inequalities in health care access.
FAU - Margarit, Cesar
AU  - Margarit C
AD  - Pain Unit, Department of Health of Alicante.
AD  - Neuropharmacology on Pain (NED) Group, Alicante Institute for Health and 
      Biomedical Research (ISABIAL-FISABIO Foundation).
FAU - Roca, Reyes
AU  - Roca R
AD  - Occupational Observatory, Miguel Hernandez University of Elche, Alicante.
FAU - Inda, Maria-Del-Mar
AU  - Inda MD
AD  - Neuropharmacology on Pain (NED) Group, Alicante Institute for Health and 
      Biomedical Research (ISABIAL-FISABIO Foundation).
FAU - Muriel, Javier
AU  - Muriel J
AD  - Neuropharmacology on Pain (NED) Group, Alicante Institute for Health and 
      Biomedical Research (ISABIAL-FISABIO Foundation).
FAU - Ballester, Pura
AU  - Ballester P
AD  - Neuropharmacology on Pain (NED) Group, Alicante Institute for Health and 
      Biomedical Research (ISABIAL-FISABIO Foundation).
FAU - Flor, Andrea
AU  - Flor A
AD  - Pain Unit, Department of Health of Alicante.
FAU - Morales, Domingo
AU  - Morales D
AD  - Operations Research Center, Miguel Hernandez University of Elche, Elche, Spain.
FAU - Peiro, Ana M
AU  - Peiro AM
AD  - Pain Unit, Department of Health of Alicante.
AD  - Neuropharmacology on Pain (NED) Group, Alicante Institute for Health and 
      Biomedical Research (ISABIAL-FISABIO Foundation).
AD  - Clinical Pharmacology Unit, Department of Health of Alicante, Alicante General 
      Hospital.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin J Pain
JT  - The Clinical journal of pain
JID - 8507389
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Receptors, Opioid, mu)
SB  - IM
MH  - Analgesics, Opioid/adverse effects
MH  - *Chronic Pain/drug therapy/genetics
MH  - Delayed Diagnosis
MH  - Female
MH  - Genotype
MH  - Humans
MH  - *Low Back Pain/drug therapy/genetics
MH  - Male
MH  - Prospective Studies
MH  - Receptors, Opioid, mu/genetics
MH  - Sexism
EDAT- 2020/03/10 06:00
MHDA- 2021/08/19 06:00
CRDT- 2020/03/10 06:00
PHST- 2020/03/10 06:00 [pubmed]
PHST- 2021/08/19 06:00 [medline]
PHST- 2020/03/10 06:00 [entrez]
AID - 10.1097/AJP.0000000000000824 [doi]
PST - ppublish
SO  - Clin J Pain. 2020 Jun;36(6):420-429. doi: 10.1097/AJP.0000000000000824.