A Genetic Association Study of the Functional A118G Polymorphism of the Human ??-Opioid Receptor Gene in Patients with Acute and Chronic Pain

Abstract

In this prospective, observational study we explored whether A118G single nucleotide polymorphism in the human mu-opioid receptor (MOR) gene could explain the inter-individual differences in opioid analgesic requirements in patients with acute postoperative pain and chronic pain. The frequency of the wild-type A118 MOR (major) and variant G118 MOR (minor) alleles in the subjects with chronic, noncancer pain (n = 121) and opioid-naïve subjects with acute postoperative pain (n = 101), serving as the control group, were examined. The relationships among the A118G MOR genotype, opioid requirements, and the numerical pain score were analyzed in both groups. The frequency of the minor allele was significantly lower in the subjects with chronic pain when compared with the group with acute postoperative pain (0.079 versus 0.158; P = 0.009 by chi2 test). No statistically significant association was observed between the presence of A118G MOR polymorphism and the average postoperative pain score or the doses of morphine used in the immediate postoperative period. In the high-quartile, opioid utilization, chronic pain patients, the homozygotic carriers of the major allele required significantly higher opioid dose than did the carriers of the minor allele. The results indicate that although the presence of the minor allele does not appear to affect opioid analgesic use in acute postoperative pain, the minor allele is less common in chronic pain patients, especially in those requiring higher doses of opioid analgesics.

Genetic variability of the μ-opioid receptor influences intrathecal fentanyl analgesia requirements in laboring women ☆

“…Our results are not consistent with findings of a handful of studies assessing the clinical efficacy and toxicity of morphine-6-glucuronide compared to morphine in subjects with 304A/G polymorphism [29,30,42], and several trials examining chronic morphine requirements in cancer patients [5,23,25] or the use of postoperative i.v. morphine via patient-controlled analgesia [10,11,14,23].…”

“…morphine via patient-controlled analgesia [10,11,14,23]. In these various settings, patients with at least one 304G allele exhibited a trend towards increased systemic morphine requirements, findings which are in the opposite direction to our results with intrathecal fentanyl.…”

“…Since labor pain is primarily caused by changes of pressure during the contractions transmitted at the level of the lower thoracic and upper lumbar segments, the experimental findings with a pressure stimulus may be more relevant. Finally, the frequency of the 304G variant has been shown to be lower in chronic pain patients as compared to controls [23], suggesting that the variant confers some analgesia or other form of "protection" against pain.…”

How Much Oxycodone Is Needed for Adequate Analgesia After Breast Cancer Surgery: Effect of the OPRM1 118A>G Polymorphism

“…In addition, many of the negative studies have had small sample sizes 4, 9, 11 or a low frequency of the G-allele. 3,15,21 Two previous studies have used a different approach to measure the effect of muopioid receptor genotype on postoperative pain. 5,36 In these studies the amount of opioids given to subjects has been standardized and the focus has been on the pain score.…”

Role of Opioidergic System in Humoral Immune Response

“…Indeed, Vassou et al (2008) have shown that opiates like morphine, alpha S1 -casomorphin and ethylketocyclazocine modulate antibody and cytokine secretion by multiple myeloma cells in a cell line-dependent manner and decrease antibody secretion by normal B-lymphocytes. Data from both transfected cells and human autopsy brain tissue from carriers of 118G allele indicate that this allele may produce deleterious effect on mRNA and corresponding MOR protein yield (Janicki et al, 2006). Based on the literature reviewed here it can be conclusively said that the complete repertoire of molecular consequence of the 118G SNP on receptor function in various immune cells and nevous tissue still remain unelucidated.…”