Genetic susceptibility to postherniotomy pain. The influence of polymorphisms in the Mu opioid receptor, TNF-α, GRIK3, GCH1, BDNF and CACNA2D2 genes

2016 ◽  
Vol 12 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Maija-Liisa Kalliomäki ◽  
Gabriel Sandblom ◽  
Mathias Hallberg ◽  
Alfhild Grönbladh ◽  
Ulf Gunnarsson ◽  
...  

AbstractBackground and aimsDespite improvements in surgical technique, 5%-8% of patients undergoing herniorrhaphy still suffer from clinically relevant persistent postherniotomy pain. This is a problem at both individual and society levels. The aim of this study was to determine whether or not a single nucleotide polymorphism in a specific gene contributes to the development of persistent pain after surgery.MethodsOne hundred individuals with persistent postherniotomy pain, along with 100 without pain matched for age, gender and type of surgery were identified in a previous cohort study on patients operated for groin hernia. All patients underwent a thorough sensory examination and blood samples were collected. DNA was extracted and analysed for single nucleotide polymorphism in the Mu opioid receptor, TNF-α, GRIK3, GCH1, BDNF and CACNA2D2 genes.ResultsPatients with neuropathic pain were found to have a homozygous single nucleotide polymorph in the TNF-α gene significantly more often than pain-free patients (P =0.036, one-tailed test). ConclusionsSNP in the TNF-α gene has a significant impact on the risk for developing PPSP.ImplicationsThe result suggests the involvement of genetic variance in the development of pain and this requires further investigation.

2007 ◽  
Vol 0 (0) ◽  
pp. 070630082917007-??? ◽  
Author(s):  
Thomas Kroslak ◽  
K. Steven LaForge ◽  
Robert J. Gianotti ◽  
Ann Ho ◽  
David A. Nielsen ◽  
...  

2002 ◽  
Vol 97 (4) ◽  
pp. 814-819 ◽  
Author(s):  
Jörn Lötsch ◽  
Michael Zimmermann ◽  
Jutta Darimont ◽  
Claudia Marx ◽  
Rafael Dudziak ◽  
...  

Background Some, but not all, patients with renal dysfunction suffer from side effects after morphine administration because of accumulation of the active metabolite morphine-6-glucuronide (M6G). The current study aims to identify genetic causes that put patients at risk for, or protect them from, opioid side effects related to high plasma M6G. Candidate genetic causes are the single nucleotide polymorphism (SNP) A118G of the mu-opioid-receptor gene (OPRM1), which has recently been identified to result in decreased potency of M6G, and mutations in the MDR1-gene coding P-glycoprotein, of which morphine and M6G might be a substrate. Methods Two men, aged 87 and 65 yr, with renal failure (creatinine clearance of 6 and 9 ml/min) received 30 mg/day oral morphine for pain treatment. Both patients had sufficient analgesia from morphine. However, while one patient tolerated morphine well despite high plasma M6G of 1735 nM, in the patient with M6G plasma concentrations of 941 nM it caused severe sleepiness and drowsiness. Patients were genotyped for known SNPs of the OPRM1 and MDR1 genes. Results The patient who tolerated morphine well despite high plasma M6G was a homozygous carrier of the mutated G118 allele of the mu-opioid-receptor gene, which has been previously related to decreased M6G potency. In contrast, the patient who suffered from side effects was "wild-type" for this mutation. No other differences were found between the OPRM1 and MDR1 genes. Conclusions The authors hypothesize that the A118G single nucleotide polymorphism of the mu-opioid-receptor is among the protective factors against M6G-related opioid toxicity. The observation encourages the search for pharmacogenetic reasons that cause interindividual variability of the clinical effects of morphine.


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