Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inadequately treated acute and chronic pain remains a major cause of suffering and dissatisfaction in pain therapy. A cause for the variable success of pharmacologic pain therapy is the different genetic disposition of patients to develop pain or to respond to analgesics. The patient's phenotype may be regarded as the result of synergistic or antagonistic effects of several genetic variants concomitantly present in an individual. Variants modulate the risk of developing painful disease or its clinical course (e.g., migraine, fibromyalgia, low back pain). Other variants modulate the perception of pain (e.g., OPRM1 or GCH1 variants conferring modest pain protection by increasing the tone of the endogenous opioid system or decreasing nitric oxide formation). Other polymorphisms alter pharmacokinetic mechanisms controlling the local availability of active analgesic molecules at their effector sites (e.g., decreased CYP2D6 related prodrug activation of codeine to morphine). In addition, genetic variants may alter pharmacodynamic mechanisms controlling the interaction of the analgesic molecules with their target structures (e.g., opioid receptor mutations). Finally, opioid dosage requirements may be increased depending on the risk of drug addiction (e.g., DRD2 polymorphisms decreasing the functioning of the dopaminergic reward system). With the complex nature of pain involving various mechanisms of nociception, drug action, drug pharmacology, pain disease and possibly substance addiction, a multigenic or even genome wide approach to genetics could be required to base individualized pain therapy on the patient's genotype.
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PMID:Genetic modulation of the pharmacological treatment of pain. 1961 6

Regard of functional pharmacogenetic polymorphisms may further the success of pain therapy by adopting individualized approaches. The mu-opioid receptor gene (OPRM1) 118A>G polymorphism is a promising candidate for both opioid effects and pain because of both biological reasonability and apparent experimental and clinical evidence. We analyzed its importance for pain therapy using a meta-analytic approach to studies relating it to opioid pain therapy. Data from suitable studies selected from hits of a PubMed search for "OPRM1" were independently extracted by two authors. The meta-analysis included phenotypes by OPRM1 genotype (opioid dosing, pain, and side effects), publication year, diagnostic status, proportion of male study participants, and whether genotype frequencies agreed with Hardy-Weinberg equilibrium. We found no consistent association between OPRM1 118A>G genotypes and most of the phenotypes in a heterogeneous set of eight clinical studies. Only weak evidence of an association with less nausea (effect size, Cohen's d=-0.21, p=0.037) and of increased opioid dosage requirements (d=0.56, p=0.018) in homozygous carriers of the G allele was obtained. This indicates that despite initially promising results, available evidence of the clinical relevance of the OPRM1 118A>G polymorphism does not withhold a meta-analysis. This discourages basing personalized therapeutic concepts of pain therapy on OPRM1 118A>G genotyping at the present state of evidence.
Pain 2009 Dec
PMID:Meta-analysis of the relevance of the OPRM1 118A>G genetic variant for pain treatment. 1967 95

Scientific understanding of social pain--the hurt feelings resulting from social rejection, separation, or loss--has been facilitated by the hypothesis that such feelings arise, in part, from some of the same neural and neurochemical systems that generate the unpleasant feelings resulting from physical pain. Accordingly, in animals, the painkiller morphine not only alleviates the distress of physical pain, but also the distress of social separation. Because morphine acts on the mu-opioid receptor, we examined whether variation in the mu-opioid receptor gene (OPRM1), as measured by the functional A118G polymorphism, was associated with individual differences in rejection sensitivity. Participants (n = 122) completed a self-report inventory of dispositional sensitivity to social rejection and a subsample (n = 31) completed a functional MRI session in which they were rejected from an online ball-tossing game played with two supposed others. The A118G polymorphism was associated with dispositional sensitivity to rejection in the entire sample and in the fMRI subsample. Consistent with these results, G allele carriers showed greater reactivity to social rejection in neural regions previously shown to be involved in processing social pain as well as the unpleasantness of physical pain, particularly the dorsal anterior cingulate cortex (dACC) and anterior insula. 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. Taken together, these data suggest that the A118G polymorphism specifically, and the mu-opioid receptor more generally, are involved in social pain in addition to physical pain.
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PMID:Variation in the mu-opioid receptor gene (OPRM1) is associated with dispositional and neural sensitivity to social rejection. 1970 72

Intensity of postoperative pain and postoperative analgesic requirements are widely varied among patients. The most determinant significant aspect of postoperative pain is the site and type of surgery. For example, open abdominal surgery usually causes intense postoperative pain. Even in patients after the same type of surgery, however, there are wide individual variations in pain intensity and analgesic requirements. A variety of environmental factors can lead to such differences. In addition, genetic factors also can contribute to such differences. For example, a single nucleotide polymorphism A118G of human micro-opioid receptor gene (OPRM1) may decrease analgesic efficacy of opioids and increase postoperative opioid requirements. Full elucidation of genetic factors that can affect pain sensitivity and/or opioid sensitivity may open new avenues for personalized pain treatment.
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PMID:[How can we cope with wide individual variations in pain intensity and opioid requirements after surgery?]. 1976 30

We experience individual differences in pain and sensitivity to analgesics clinically. Genetic factors are known to influence individual difference. Polymorphisms in the human OPRM1 gene, which encodes the micro-opioid receptors, may be associated with the clinical effects of opioid analgesics. The study demonstrated whether any of five common single nucleotide polymorphisms (SNPs) of the OPRM1 gene could affect the antinociceptive effect of fentanyl. Fentanyl was less effective in subjects with the G allele of the OPRM1 A118G SNP than those with the A allele, and subjects with the G allele required more fentanyl for adequate postoperative pain control than those with the A allele. In the future, identifying SNPs might give us information to modulate the analgesic dosage of opioid individually for better pain control.
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PMID:[Postoperative pain management following orthognathic surgery in consideration of individual differences--is the antinociceptive effect of fentanyl related to the genotype involving nucleotide at OPRM1?]. 1976 32

A multiple primer extension (MPEX) was originally developed for the hybridization, extension, and amplification of a DNA template on a planar substrate by Kinoshita et al. in 2006. Herein we present a modified MPEX method refined by our group for single nucleotide polymorphism (SNP) detection. In this method, hybridization and extension reactions are performed on a plastic S-BIO PrimeSurface substrate, with a biocompatible polymer. Its surface chemistry offers extraordinarily stable thermal properties, as well as chemical properties advantageous for enzymatic reactions on the surface. To visualize allele-specific PCR products on the surface, biotin-dUTP was incorporated into newly synthesized complementary strands during the extension reaction. The products were ultimately detected by carrying out a colorimetric reaction with a substrate solution containing 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium. We have further successfully combined this method with multiplex PCR. We demonstrate the advantages of this combined method by analyzing representative SNPs on different linkage disequilibrium blocks of the micro opioid receptor gene (OPRM1), which is a marker gene for pain threshold.
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PMID:Modified multiple primer extension method. 1976 10

Genetic risk factors for pain sensitivity may also play a role in susceptibility to chronic pain disorders, in which subjects have low pain thresholds. The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and mu opioid receptor (OPRM1) genes previously associated with pain sensitivity affect susceptibility to chronic widespread pain (CWP). Pain data was collected using body manikins via questionnaire at three time-points over a four year period from subjects aged 25-65 in the North-West of England as part of a population based cohort study, EPIFUND. CWP was defined at each time point using standard criteria. Three SNPs forming a proposed "pain-protective" haplotype in GCH1 (rs10483639, rs3783641 and rs8007267) and two SNPs in OPRM1 (rs1777971 (A118G) and rs563649) were genotyped in cases with persistent CWP (CWP present at >or=2 time-points) and controls who were pain-free at all time-points. The expectation-maximisation algorithm was used to estimate haplotype frequencies. The frequency of the "pain-protective" (CAT - C allele of rs10483639, A allele of rs3783641 and T allele of rs8007267) haplotype was compared to the frequency of the other haplotypes between cases and controls using the chi2 test. Allele frequencies and carriage of the minor allele was compared between cases and controls using chi2 tests for the OPRM1 SNPs. The frequency of the proposed GCH1 "pain-protective" haplotype (CAT) did not significantly differ between cases and controls and no significant associations were observed between the OPRM1 SNPs and CWP. In conclusion, there was no evidence of association between proposed functional SNPs, previously reported to influence pain sensitivity, in GCH1 and OPRM1 with CWP. Further evidence of null association in large independent cohorts is required to truly exclude these SNPs as genetic risk factors for CWP.
Mol Pain 2009 Sep 23
PMID:Do genetic predictors of pain sensitivity associate with persistent widespread pain? 1977 52

Individual differences in sensitivity to fentanyl, a widely used opioid analgesic, can hamper effective pain treatment. Still controversial is whether the single nucleotide polymorphisms (SNPs) of the human OPRM1 gene encoding the mu-opioid receptor influence the analgesic effects of opioids. We examined associations between fentanyl sensitivity and the two SNPs, A118G and IVS3+A8449G, in the human OPRM1 gene in 280 Japanese patients undergoing painful orofacial cosmetic surgery, including bone dissection. 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). Furthermore, the IVS3+A8449G SNP in intron 3, which represents a complete linkage disequilibrium block with more than 30 SNPs from intron 3 to the 3' untranslated region, was associated with 24-h postoperative fentanyl requirements. Subjects carrying the minor G allele of the IVS3+A8449G SNP required significantly less fentanyl for 24-h postoperative pain control (median: 1.5microg/kg) compared with subjects not carrying this allele (median: 2.5microg/kg, p=0.010). Although further validation is needed, the present findings shed light on the involvement of OPRM1 3' untranslated region polymorphisms in fentanyl sensitivity in addition to the A118G SNP and open new avenues for personalized pain treatment with fentanyl.
Pain 2009 Dec 15
PMID:Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery. 1978 98

The aim of this study was to search for a possible association between the variant allele of the single nucleotide polymorphisms A118G in the OPRM1 gene and C3435T and G2677T/A in the ABCB1 gene and altered antinociceptive effect and adverse drug reactions of oxycodone. Thirty-three healthy subjects exposed to experimental pain including electrical stimulation and the cold pressor test were included. 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). C3435T: The carriers of the variant T allele generally had less adverse drug reactions on oxycodone than the carriers of the wild-type genotype. G2677T/A: The carriers of the variant T allele had a better antinociceptive effect of oxycodone than the carriers of the wild-type genotype in the cold pressor test (25% reduction vs. 15%, P = 0.015 in the discomfort rating and 25% reduction vs. 12%, P = 0.007 in the pain time AUC) and less adverse drug reactions. The combined wild-type genotype 3435CC-2677GG was associated with less antinociceptive effect of oxycodone in the discomfort rating of the cold pressor test (13% reduction vs. 23%, P = 0.019) and more severe adverse drug reactions than the carriers of the variant alleles. We found a moderate association between less antinociceptive effect of oxycodone and the variant allele of A118G. There was strong association between less adverse drug reactions of oxycodone and the variant alleles of C3435T and G2677T/A.
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PMID:The antinociceptive effect and adverse drug reactions of oxycodone in human experimental pain in relation to genetic variations in the OPRM1 and ABCB1 genes. 1984 69

One hundred and seventy-four Chinese gynaecology patients were studied for the impact of A118G polymorphism in the micro-opioid receptor gene (OPRM1) on pain sensitivity and postoperative fentanyl consumption. Pre-operatively, the pain threshold and pain tolerance threshold were measured using electrical stimulation. A118G polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Intravenous fentanyl patient-controlled analgesia provided postoperative pain management, assessed using a visual analogue scale and fentanyl consumed in the first 24 h after surgery was noted. We found the prevalence of G118 allele was 31.3%. The A118G polymorphism had a gene-dose-dependent effect on electrical pain tolerance threshold. Fentanyl consumption was also significantly different in patients with different OPRM1 genotypes (homozygotes for 118G consumed more than did heterozygotes or homozygotes for 118A). Fentanyl consumption increased in accordance with the number of 118G alleles. We conclude that OPRM1 gene analysis may help predict individual opioid sensitivity and so optimise postoperative pain control.
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PMID:Association of human micro-opioid receptor gene polymorphism A118G with fentanyl analgesia consumption in Chinese gynaecological patients. 2000 18


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