A118G single nucleotide polymorphism of human mu-opioid receptor gene influences pain perception and patient-controlled intravenous morphine consumption after intrathecal morphine for postcesarean analgesia.
A118G: We found that the variant G allele was associated with reduced antinociceptive effect as measured by pain tolerance thresholds to single electrical nerve stimulation (8% increase vs. 25% for the wild-type carriers, P = 0.007).
A common single nucleotide polymorphism (SNP), A118G, in the mu-opioid receptor gene can affect opioid function and, consequently, has been suggested to contribute to individual variability in pain management and drug addiction.
A single nucleotide polymorphism (SNP) in the human mu-opioid receptor gene (OPRM1 A118G) has been widely studied for its association in a variety of drug addiction and pain sensitivity phenotypes; however, the extent of these adaptations and the mechanisms underlying these associations remain elusive.
Accordingly, a functional μ-opioid receptor (OPRM1) polymorphism (C77G in primates, A118G in humans) affecting opioidergic signaling has been associated with separation distress and attachment behavior in nonhuman primates, and social pain sensitivity in humans.
Additionally, the combined genotype of CYP3A4*18B and OPRM1 A118G may affect fentanyl doses administered for pain control, but not postoperative nausea, vomiting and dizziness.
Few associations replicated: morphine dose (mcg/kg) in African American children and ABCB1 rs1045642 (A allele, β = -9.30, 95% CI: -17.25 to -1.35, p = 0.02) and OPRM1 rs1799971 (G allele, β = 23.19, 95% CI: 3.27-43.11, p = 0.02); KCNJ6 rs2211843 and high pain in African American subjects (T allele, OR 2.08, 95% CI: 1.17-3.71, p = 0.01) and in congruent European Caucasian pain phenotypes; and COMT rs740603 for high pain in European Caucasian subjects (A allele, OR: 0.69, 95% CI: 0.48-0.99, p = 0.046).
For patients with no copies of the LPS haplotype, AA of OPRM1 A118G was significantly associated with higher pain scores compared to the variant AG/GG.
Furthermore, dACC activity mediated the relationship between the A118G polymorphism and dispositional sensitivity to rejection, suggesting that this is a critical site for mu-opioid-related influence on social pain.
Genetic variants in OPRM1, particularly the non-synonymous polymorphism A118G, have been repeatedly associated with the efficacy of treatments for pain and various types of dependence.
In a subpopulation, identifying OPRM1 A118G polymorphism may provide valuable information regarding the individual analgesic doses that are required to achieve satisfactory pain control.
In addition, given the prominent role of the opioid system in pain signaling, we investigated the effects of acute alcohol exposure on PIP5K1C expression in humanized transgenic mice for the μ-opioid receptor that included the OPRM1 A118G polymorphism, a widely used mouse model to study analgesic response to opioids in pain.
In comparison, two pain-related gene SNPs (OPRM1 [rs1799971] and COMT [rs4818]) interacted with psychological factors to predict four shoulder impairment phenotypes (abduction: 5-day average loss; strength loss: 5-day average, peak, and relative loss).
In line with suggestions of a common neural network involved in the processing of physical pain and negative and distressing stimuli, like social rejection as a psychologically harmful event, we examined the influence of the A118G polymorphism on the neural processing of physical and non-physical pain.
In subgroup analysis, we did not find statistically significant correlation between OPRM1 A118G polymorphism and opioid pain relief among Caucasian patients (SMD=-0.15; 95% CI, -0.29 to -0.00; P=0.04), as well as among morphine users (SMD =-0.20; 95% CI, -0.40 to 0.00, P=0.05), except for Asian patients (SMD=-0.42; 95% CI, -0.62 to -0.23; P<0.001).
Logistic regression analysis adjusting for age effects showed the A118G SNP of the OPRM1 gene to be significantly associated with migraine pain severity in the test population (P = 0.0037).
No difference was observed between fibromyalgia patients with and without the A118G allele with regard to the Beck Depression Inventory, widespread pain index, symptom severity, and Fibromyalgia Impact Questionnaire scores.
Our previous data revealed significantly higher pressure pain thresholds among individuals possessing the minor G allele of the A118G SNP of the mu-opioid receptor gene (OPRM1) compared with those with 2 consensus alleles.
Our results demonstrate that the A118G OPRM1 polymorphism contributes to interindividual variations in the function of neurotransmitters responsive to pain (endogenous opioid and dopamine), as well as their regulation through cognitive-emotional influences in the context of therapeutic expectations, the so-called placebo effect.
Our results suggest that ethnicity and OPRM 118A>G genotype are independent and significant contributors to variation in pain perception and postoperative morphine use in patients undergoing cesarean delivery.
Patients homozygous for the variant G allele of the 118 A > G polymorphism (n = 4) needed more morphine to achieve pain control, compared to heterozygous (n = 17) and homozygous wild-type (n = 78) individuals.
Polymorphisms of OPRM1 A118G and ABCB1 C3435T have been suggested to contribute to inter-individual variability regarding pain sensitivity, opioid usage, tolerance and dependence and incidence of adverse effects in patients with chronic pain.