b3dfbbf28330af6d6cda820d80dd81fc 337140.pdf e3a8f19d74557fbd56a2fff51aa830061403347e 337140.pdf 2fe822b29d551d5bf70c1f656aec621eb5c3d5fc59a00b78e5cd91d0018febd2 337140.pdf Title: The Role of Pharmacogenetic Biomarkers in Pain Subject: Background/Objectives: Pain—whether acute, chronic, or neuropathic—remains a leading cause of disability and reduced quality of life worldwide. Despite advances in pharmacologic options, interindividual variability in response and susceptibility to adverse effects continues to challenge clinicians. In recent years, pharmacogenetics has emerged as a promising approach to optimize analgesic selection and dosing based on patient-specific genetic profiles. This perspective examines current pharmacogenetic evidence in pain management, focusing on validated biomarkers and their clinical implications. Methods: A narrative review was conducted of recent literature addressing the impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of analgesic agents. Particular focus was given to genes involved in drug metabolism and transport as well as receptor signaling, along with the clinical applications of genotype-informed prescribing. Results: Substantial evidence indicates that genetic variants significantly influence patient responses to analgesics, contributing to both inadequate pain relief and heightened sensitivity to adverse effects. The main pharmacogenetic biomarkers appear to be CYP2C9 (for NSAIDs), CYP2D6 (for opioids and tricyclic antidepressants), CYP2C19 (for tricyclic antidepressants) and HLA-B*15:02 and HLA-A*31:01 for carbamazepine. PGx-informed strategies have shown promise in improving analgesic effectiveness, reducing opioid-related complications, and supporting opioid-sparing protocols. Conclusions: Pharmacogenetic screening represents a valuable tool for personalizing pain management. Incorporating validated pharmacogenetic biomarkers into clinical practice could improve treatment outcomes and patient safety. Further research, infrastructure development, and clinician education are essential for scaling PGx implementation in pain care. Keywords: pharmacogenetics; pain; opioids; NSAIDs; tricyclic antidepressants Author: Ivan Martin da Silva, Adrián Plaza-Díaz, Jesus Ruiz-Ramos, Ana Juanes-Borrego and Pau Riera Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Fri Aug 8 12:08:37 2025 CEST ModDate: Fri Aug 8 12:10:05 2025 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 474295 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ODOVUW+URWPalladioL-Roma Type 1 Custom yes yes yes 119 0 OEOOXW+URWPalladioL-Ital Type 1 Custom yes yes yes 120 0 SZMXAO+URWPalladioL-Bold Type 1 Custom yes yes yes 121 0 IPPPBA+PalatinoLinotype TrueType WinAnsi yes yes no 149 0 JGMOZW+CMSY10 Type 1 Builtin yes yes yes 181 0 ZZJXSH+EURM10 Type 1 Builtin yes yes yes 214 0 MPUDFL+PazoMath Type 1 Builtin yes yes yes 362 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2026-10-29 04:09:05 CET RepresentationInformation: 337140.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2026-10-28 17:11:23 CET Size: 474295 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 474 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Pharmacogenetic Biomarkers in Analgesia Children: Item: Title: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Item: Title: Opioids Item: Title: Antidepressants, Anticonvulsants, and Gabapentinoids Children: Item: Title: Tricyclic Antidepressants (TCAs) Item: Title: Anticonvulsants: Carbamazepine and Oxcarbazepine Item: Title: Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) and Selective Serotonin Reuptake Inhibitors (SSRIs) Item: Title: Gabapentinoids: Gabapentin and Pregabalin Item: Title: Clinical Implications and Future Perspectives Children: Item: Title: From Single-Gene Testing to Multi-Omic Pain Signatures Item: Title: Implementation Science and Real-World Pragmatism Item: Title: Clinical Decision Support (CDS) That Clinicians Will Use Item: Title: Equity, Ancestry, and Allele Frequency Gaps Item: Title: Digital Phenotyping and AI-Driven Dosing Item: Title: Real-World Evidence (RWE) and Health–Economic Data Item: Title: Conclusions Item: Title: References Info: Title: The Role of Pharmacogenetic Biomarkers in Pain Author: Ivan Martin da Silva, Adrián Plaza-Díaz, Jesus Ruiz-Ramos, Ana Juanes-Borrego and Pau Riera Subject: Background/Objectives: Pain—whether acute, chronic, or neuropathic—remains a leading cause of disability and reduced quality of life worldwide. Despite advances in pharmacologic options, interindividual variability in response and susceptibility to adverse effects continues to challenge clinicians. In recent years, pharmacogenetics has emerged as a promising approach to optimize analgesic selection and dosing based on patient-specific genetic profiles. This perspective examines current pharmacogenetic evidence in pain management, focusing on validated biomarkers and their clinical implications. Methods: A narrative review was conducted of recent literature addressing the impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of analgesic agents. Particular focus was given to genes involved in drug metabolism and transport as well as receptor signaling, along with the clinical applications of genotype-informed prescribing. Results: Substantial evidence indicates that genetic variants significantly influence patient responses to analgesics, contributing to both inadequate pain relief and heightened sensitivity to adverse effects. The main pharmacogenetic biomarkers appear to be CYP2C9 (for NSAIDs), CYP2D6 (for opioids and tricyclic antidepressants), CYP2C19 (for tricyclic antidepressants) and HLA-B*15:02 and HLA-A*31:01 for carbamazepine. PGx-informed strategies have shown promise in improving analgesic effectiveness, reducing opioid-related complications, and supporting opioid-sparing protocols. Conclusions: Pharmacogenetic screening represents a valuable tool for personalizing pain management. Incorporating validated pharmacogenetic biomarkers into clinical practice could improve treatment outcomes and patient safety. Further research, infrastructure development, and clinician education are essential for scaling PGx implementation in pain care. 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