Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Catechol-O-methyltransferase (COMT) polymorphisms modulate pain and opioid analgesia in human beings. It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level.
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PMID:Stress-induced analgesia and morphine responses are changed in catechol-O-methyltransferase-deficient male mice. 1883 57

Increased pain sensitivity after opioid administration (opioid-induced hyperalgesia) and/or repeated painful stimuli is an individually varying and clinically important phenomenon. The functional polymorphism (val(158)met) of the Catechol-O-methyltransferase (COMT) gene regulates the metabolism of dopamine/noradrenaline. Individuals homozygous for the met(158) allele have been reported to have increased pain sensitivity and there are findings of lower micro-opioid system activation during sustained pain. We hypothesized that met/met individuals would exhibit higher pain sensitization and opioid-induced hyperalgesia in response to repeated pain stimuli and an intravenous injection of an opioid drug. Participants were 43 healthy subjects who went through an experiment where five blocks of pain were induced to the hand using a heat probe. After each stimulus subjects rated the pain on a visual analogue scale (VAS) from 0 mm (no pain) to 100 mm (worst possible pain). Before the second stimulus there was an intravenous injection of a rapid and potent opioid drug. At baseline there was no difference in pain ratings between the COMTval(158)met genotypes, F(2, 39)<1. However, a repeated measures ANOVA for all five stimuli revealed a main effect for COMTval(158)met genotype, F(2, 36) = 4.17, p = 0.024. Met/met individuals reported significantly more pain compared to val/val, p = 0.010. A pairwise comparison of baseline and the opioid intervention demonstrated that analgesia was induced in all groups (p = 0.042) without a separating effect for genotype (n.s). We suggest that the initial response of the descending pain system is not influenced by the COMTval(158)met polymorphism but when the system is challenged the difference is revealed. An important clinical implication of this may be that the COMTval(158)met related differences may be more expressed in individuals where the inhibitory system is already challenged and sensitive, e.g. chronic pain patients. This has to be proven in future studies where the impact of the COMTval(158)met polymorphism on opioid treatment in patients is addressed.
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PMID:Increased sensitivity to thermal pain following a single opiate dose is influenced by the COMT val(158)met polymorphism. 1954 55

Catechol-O-methyltransferase (COMT) gene polymorphisms and haplotypes have been associated with both experimental and clinical pain phenotypes. In this prospective study, we investigated the association of three common polymorphisms with experimentally induced pressure pain, postoperative pain and amount of self-administered morphine in 973 patients who underwent scheduled total hysterectomy. DNA extracted from peripheral blood was genotyped for three COMT polymorphisms by Taqman assay or a PCR-based method. In the overall sample, rs4633 and rs4680 were significantly associated with morphine use, whereas rs4818 was associated with time-averaged pain scores. Statistically significant associations were found between COMT rs4633 and rs4680 genotypes and the amount of morphine self-administered through a patient-controlled analgesia pump. For rs4818, the only statistically significant association was with time-averaged pain scores. Haplotype analysis showed statistically significant association of the low pain sensitivity haplotype with time-averaged pain scores; and average pain sensitivity haplotype with total morphine and weight-adjusted morphine.
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PMID:Common variants of catechol-O-methyltransferase influence patient-controlled analgesia usage and postoperative pain in patients undergoing total hysterectomy. 2596 35