Are catechol-O-methyltransferase gene polymorphisms genetic markers for pain sensitivity after all? – A review and meta-analysis

Vetterlein, Annabel; Monzel, Merlin; Reuter, Martin

doi:10.1016/j.neubiorev.2023.105112

Cited by 10 publications

(6 citation statements)

References 128 publications

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“…These variations are very common (approximately one in every thousand base pairs in the human genome), and account for 90% of all human genetic variation. SNPs underlie differences in susceptibility to many diseases, including some inducing pain, and can modify pain thresholds especially when pain modulatory pathways are challenged (Vetterlein et al, 2023); it is, therefore, conceivable that they may contribute to the heterogeneity of response to rTMS. Since monoaminergic mechanisms modulate pain responses, and polymorphisms in dopamine-related genes can change functional connectivity following rTMS (Hong et al, 2023), a number of authors assessed the influence of the dopamine (DRD2) and COMT gene polymorphisms on the rTMS analgesic effect.…”

Section: Candidates?mentioning

confidence: 99%

Beyond trial‐and‐error: Individualizing therapeutic transcranial neuromodulation for chronic pain

Ciampi de Andrade,

García‐Larrea

2023

European Journal of Pain

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Background and ObjectiveRepetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex provides supplementary relief for some individuals with chronic pain who are refractory to pharmacological treatment. As rTMS slowly enters treatment guidelines for pain relief, its starts to be confronted with challenges long known to pharmacological approaches: efficacy at the group‐level does not grant pain relief for a particular patient. In this review, we present and discuss a series of ongoing attempts to overcome this therapeutic challenge in a personalized medicine framework.Databases and Data TreatmentRelevant scientific publications published in main databases such as PubMed and EMBASE from inception until March 2023 were systematically assessed, as well as a wide number of studies dedicated to the exploration of the mechanistic grounds of rTMS analgesic effects in humans, primates and rodents.ResultsThe main strategies reported to personalize cortical neuromodulation are: (i) the use of rTMS to predict individual response to implanted motor cortex stimulation; (ii) modifications of motor cortex stimulation patterns; (iii) stimulation of extra‐motor targets; (iv) assessment of individual cortical networks and rhythms to personalize treatment; (v) deep sensory phenotyping; (vi) personalization of location, precision and intensity of motor rTMS. All approaches except (i) have so far low or moderate levels of evidence.ConclusionsAlthough current evidence for most strategies under study remains at best moderate, the multiple mechanisms set up by cortical stimulation are an advantage over single‐target ‘clean’ drugs, as they can influence multiple pathophysiologic paths and offer multiple possibilities of individualization.SignificanceNon‐invasive neuromodulation is on the verge of personalised medicine. Strategies ranging from integration of detailed clinical phenotyping into treatment design to advanced patient neurophysiological characterisation are being actively explored and creating a framework for actual individualisation of care.

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Section: Candidates?mentioning

confidence: 99%

Beyond trial‐and‐error: Individualizing therapeutic transcranial neuromodulation for chronic pain

Ciampi de Andrade,

García‐Larrea

2023

European Journal of Pain

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“…This involves a guanosine (G) to adenosine (A) transition, resulting in a valine (Val) to methionine (Met) amino acid substitution. This substitution may lead to three possible SNP genotypes: GG (Val/Val) genotype, characterized by high enzymatic activity; AA (Met/Met) genotype, associated with defective enzymes; and GA (Val/Met) genotype, demonstrating moderate enzymatic activity [67,68]. In the existing literature, three primary haplotypes have shown a strong correlation with sensitivity to experimental pain [69].…”

Section: Comtmentioning

confidence: 99%

Pharmacogenetic Approaches in Personalized Medicine for Postoperative Pain Management

Ferreira do Couto,

Fonseca,

Pozza

2024

Biomedicines

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Despite technical and pharmacological advancements in recent years, including optimized therapies and personalized medicine, postoperative pain management remains challenging and sometimes undertreated. This review aims to summarize and update how genotype-guided therapeutics within personalized medicine can enhance postoperative pain management. Several studies in the area have demonstrated that genotype-guided therapy has the ability to lower opioid consumption and improve postoperative pain. Gene mutations, primarily OPRM1, CYP2D6, CYP2C9, COMT and ABCB1, have been shown to exert nuanced influences on analgesic response and related pharmacological outcomes. This review underscores the integration of pharmacogenetic-guided personalized medicine into perioperative care, particularly when there is uncertainty regarding opioid prescriptions. This approach leads to superior outcomes in terms of postoperative pain relief and reduced morbidity for numerous patients.

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“…COMT is an important enzyme involved in opioid metabolism, particularly relevant for drugs like morphine. Genetic variants in the COMT gene result in different enzyme activities, impacting the breakdown of catecholamine neurotransmitters [ 31 , 34 ]. The metabolism of catecholamine neurotransmitters by COMT is pivotal in pain response modulation.…”

Section: Pharmacogenomics and Enzyme-mediated Opioid Activitiesmentioning

confidence: 99%

“…However, their efficacy and side effects can vary widely among individuals, partly due to differences in opioid metabolism. COMT , by metabolising catecholamines, indirectly influences the availability of endogenous opioids, such as endorphins, enkephalins, and dynorphins, which are involved in pain modulation [ 22 , 31 , 34 ].…”

Section: Pharmacogenomics and Enzyme-mediated Opioid Activitiesmentioning

confidence: 99%

Opioid Monitoring in Clinical Settings: Strategies and Implications of Tailored Approaches for Therapy

Rosendo,

Rosado,

Zandonai

et al. 2024

IJMS

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This review emphasises the importance of opioid monitoring in clinical practice and advocates for a personalised approach based on pharmacogenetics. Beyond effectively managing pain, meticulous oversight is required to address concerns about side effects, specially due to opioid-crisis-related abuse and dependence. Various monitoring techniques, along with pharmacogenetic considerations, are critical for personalising treatment and optimising pain relief while reducing misuse and addiction risks. Future perspectives reveal both opportunities and challenges, with advances in analytical technologies holding promise for increasing monitoring efficiency. The integration of pharmacogenetics has the potential to transform pain management by allowing for a precise prediction of drug responses. Nevertheless, challenges such as prominent pharmacogenetic testing and guideline standardisation persist. Collaborative efforts are critical for transforming scientific advances into tangible improvements in patient care. Standardised protocols and interdisciplinary collaboration are required to ensure consistent and evidence-based opioid monitoring. Future research should look into the long-term effects of opioid therapy, as well as the impact of genetic factors on individual responses, to help guide personalised treatment plans and reduce adverse events. Lastly, embracing innovation and collaboration can improve the standard of care in chronic pain management by striking a balance between pain relief and patient safety.

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Are catechol-O-methyltransferase gene polymorphisms genetic markers for pain sensitivity after all? – A review and meta-analysis

Cited by 10 publications

References 128 publications

Beyond trial‐and‐error: Individualizing therapeutic transcranial neuromodulation for chronic pain

Beyond trial‐and‐error: Individualizing therapeutic transcranial neuromodulation for chronic pain

Pharmacogenetic Approaches in Personalized Medicine for Postoperative Pain Management

Opioid Monitoring in Clinical Settings: Strategies and Implications of Tailored Approaches for Therapy

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