Masui. The Japanese journal of anesthesiology
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We experience individual differences in pain and sensitivity to analgesics clinically. Genetic factors are known to influence individual difference. ⋯ 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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Extracellular adenosine 5'triphosphate (ATP) has been recognized as a neurotransmitter and/or neuromodulater in the nervous systems, through acting on specific receptors, P2 purinergic receptors on the cell surface. P2 purinergic receptors are divided into two classes; P2X receptors, which are ATP-gated cation channels and subdivided into seven subtypes, and P2Y receptors, which are heptahelical G-protein coupled receptors and subdivided into eight subtypes. Recent studies revealed that ATP and its receptors are involved in peripheral and central nociceptive transmissions, including the mechanism of neuropathic pain. ⋯ Further, some of the SNPs have been revealed to cause changes of receptor functions. Our recent study showed one of these SNPs tends to be associated with the pain sensitivity induced by the cold stimuli. Association studies of these polymorphisms in the gene encoding P2X and P2Y receptors with the pain sensitivity and effects of analgesics may provide novel and useful suggestions for personalized pain managements.
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It has been known widely that sensitivity to pain and opioid analgesics varies widely among individual subjects. Because of this variability, a dose of an opioid analgesic that can produce satisfactory pain relief without adverse effects in some patients might cause underdosing or overdosing in other patients, which is often problematic in the clinic. ⋯ Further, many technologies of genotyping polymorphisms, most often single nucleotide polymorphisms (SNPs), have been developed and advanced, leading to accelerated understanding of many associations between various genetic polymorphisms and sensitivity to pain and opioids. In this article, we review the evidence of these associations accumulated thus far.
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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. ⋯ 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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There are gene polymorphisms changing the expression or activation of the serotonin (5-HT) receptors, which are associated with pain. This review showed an availability of 5-HT2A receptor gene polymorphism in analgesic sensitivity. To search gene polymorphisms related to analgesic sensitivity is important to further effective pain management. In future 5-HT2A receptor gene polymorphisms, together with polymorphisms of other genes, may greatly contribute to effective postoperative pain management and personalized medicine.