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.
The results indicate that among the genetic SNPs we studied which include those affecting analgesic drug metabolism, transport of analgesic agents across the blood-brain barrier, and their activity at target receptors and ion channels and in the modulation of neurotransmitter pathways, the A118G allele variant of OPRM1 has the most potent influence on pain management of postoperative patients.
Regarding the A118G SNP in exon 1, in a cold pressor-induced pain test before surgery, less analgesic effects of fentanyl were shown in subjects carrying the minor G allele of the A118G SNP (median of difference between pain perception latencies before and after fentanyl injection [PPLpost-PPLpre]: 12s) compared with subjects not carrying this allele (PPLpost-PPLpre: 15s, p=0.046).
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.
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.
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 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).
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.
The A118G polymorphism of mu-opioid receptor may be closely associated with DFU pain in 34 out of 50 patients in the painless group and in 5 out of 15 patients in the painful group.
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.
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.
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).
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).
Several studies have shown that human carriers of the single nucleotide polymorphism of the μ-opioid receptor, OPRM1 A118G, exhibit greater drug and alcohol use, increased sensitivity to pain, and reduced sensitivity to the antinociceptive effects of opiates.
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.