Pharmacogenomics of pain

INTRODUCTION: Opioids are commonly used for perioperative analgesia, yet children still suffer high rates of severe post-surgical pain and opioid-related adverse effects. Persistent and severe acute surgical pain greatly increases the child's chances of chronic surgical pain, long-term opioid use, and opioid use disorder. AREAS COVERED: Enhanced recovery after surgery (ERAS) protocols, are often inadequate in treating a child's severe surgical pain. Research suggests that 'older' and longer-acting opioids such as methadone are providing better methods to treat acute post-surgical pain...

Pharmacogenomics (PGx) can facilitate the transition to patient-specific drug regimens and thus improve their efficacy and reduce toxicity. The aim of this study was to evaluate the overlap of PGx classification for drug absorption, distribution, metabolism, and elimination (ADME)-related genes in the U.S. Food and Drug Administration (FDA) PGx labeling and in the Clinical Pharmacogenetics Implementation Consortium (CPIC) database. FDA-approved drugs and PGx labeling for ADME genes were identified in the CPIC database...

The objective of this case report is to illustrate pharmacogenomics (PGx)-guided oxycodone treatment, given the conflicting data on the analgesic response from oxycodone in Cytochrome P450 (CYP)2D6 poor metabolizers (PMs). PGx-guided therapy can help improve treatment outcomes. This case report describes a 58-year-old patient who was prescribed oxycodone for chronic pain management. The patient presented with a history of inadequate pain control despite analgesic treatment with oxycodone (morphine milliequivalent [MME] = 22...

The objective of this aims to demonstrate the advantage of a pharmacogenomics (PGx)-informed medication review in mitigating adverse drug events (ADEs) and optimizing therapeutic outcomes. PGx testing and PGx-informed medication reviews assist in mitigating ADEs. PGx testing was performed on a 68-year-old male presenting with uncontrolled chronic pain. The PGx results highlighted a drug-gene interaction, aiding in identification of the increased risk of statin-associated muscle symptoms (SAMS) attributing to uncontrolled chronic pain...

OBJECTIVES: The aim of this prospective study was to compare perioperative opioid use in women by status of CYP2D6, a highly polymorphic pharmacogene relevant to opioid metabolism. METHODS: Patients undergoing laparotomy were prospectively recruited and provided a preoperative saliva swab for a pharmacogenomic (PGx) gene panel. Postoperative opioid usage and pain scores were evaluated via chart review and a phone survey. Pharmacogenes known to be relevant to opioid metabolism were genotyped, and opioid metabolizing activity predicted by CYP2D6 genotyping...

INTRODUCTION: The polymorphism of the gene coding mu-opioid receptor ( OPRM1 ) is one of the factors contributing to the variability in the response to opioid analgesics in children. The goal of this study is to investigate its role in association with postoperative acute pain in children of various ages. METHODS: This prospective study analyzed 110 pediatric patients, after plastic or orthopedic surgery, who were genotyped and randomly assigned to receive fentanyl or alfentanil...

OBJECTIVE: To characterize the circadian features of the trigeminal ganglion in a mouse model of headache. BACKGROUND: Several headache disorders, such as migraine and cluster headache, are known to exhibit distinct circadian rhythms of attacks. The circadian basis for these rhythmic pain responses, however, remains poorly understood. METHODS: We examined trigeminal ganglion ex vivo and single-cell cultures from Per2::LucSV reporter mice and performed immunohistochemistry...

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that has a significant impact on quality of life and work capacity. Treatment of RA aims to control inflammation and alleviate pain; however, achieving remission with minimal toxicity is frequently not possible with the current suite of drugs. This review aims to summarise current treatment practices and highlight the urgent need for alternative pharmacogenomic approaches for novel drug discovery. These approaches can elucidate new relationships between drugs, genes, and diseases to identify additional effective and safe therapeutic options...

Aim: Associations between gene variants and opioid net effect are unclear. We conducted an exploratory pharmacogenetic analysis of 35 gene variants and opioid response in advanced cancer. Patients & methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects) and DNA (blood). Negative binomial regression and logistic regression were used. Results: Within 54 participants, eight statistically significant associations (p = 0.002-0.038) were observed between gene variants and opioid dose, pain scores or adverse effects, the majority being within the neuroimmune TLR4 pathway (IL1B [rs1143634], IL2 [rs2069762], IL6 [rs1800795], BDNF [rs6265]) and ARRB2 pathway (ARRB2 [rs3786047], DRD2 [rs6275])...

BACKGROUND: This prospective, observational study was designed to assess the phenotype variation of the genes associated with pain and opioid use following total knee arthroplasty in comparison to psycho-social elements. METHODS: Preoperative demographic data and Patient-Reported Outcomes Measurement Information System (PROMIS)-43 scores were obtained on 305 elective total knee arthroplasty patients. Patient visual analog scale (VAS) pain scores and opioid use were extracted from the hospital record...

BACKGROUND: How variations predicted by pharmacogenomic testing to alter drug metabolism and therapeutic response affect outcomes for patients with disorders of gut- brain interaction is unclear. AIMS: To assess the prevalence of pharmacogenomics-predicted drug-gene interactions and symptom outcomes for patients with disorders of gut-brain interaction. METHODS: Patients who were treated in our clinical practice for functional dyspepsia/bowel disorder underwent pharmacogenomic testing...

Sickle cell disease (SCD) is a prevalent and complex inherited pain disorder that can manifest as acute vaso-occlusive crises (VOC) and/or chronic pain. Despite their known risks, opioids are often prescribed routinely and indiscriminately in managing SCD pain, because it is so often severe and debilitating. Integrative medicine strategies, particularly non-opioid therapies, hold promise in safe and effective management of SCD pain. However, the lack of evidence-based methods for managing SCD pain hinders the widespread implementation of non-opioid therapies...

INTRODUCTION: Individual genetic variation may influence clinical effects for pain medications. Effects of CYP2C9, CYP3A4, and CYP2D6 polymorphisms on clinical effectiveness and safety for ibuprofen and oxycodone were studied. OBJECTIVE: Primary objectives were to AU2 evaluate if allelic variations would affect clinical effectiveness and adverse events (AEs) occurrence. METHODS: This pragmatic prospective, observational cohort included children aged 4 to 16 years who were seen in a pediatric emergency department with an acute fracture and prescribed ibuprofen or oxycodone for at-home pain management...

With the trend towards promoting personalised medicine (PM), the application of pharmacogenetics and pharmacogenomics (PGx) is of growing importance. For the purposes of clinical trials, the inclusion of PGx is an additional tool that should be considered for improving our knowledge about the effectiveness and safety of new drugs. A search of available clinical trials containing pharmacogenetic and PGx information was conducted on ClinicalTrials.gov. The results show there has been an increase in the number of trials containing PGx information since the 2000 s, with particular relevance in the areas of Oncology (28...

Perioperative lidocaine (lignocaine) infusions are being employed with increasing frequency. The determinants of systemic lidocaine concentrations during prolonged administration are unclear. In the Long-term Outcomes after Lidocaine Infusions for PostOperative Pain (LOLIPOP) pilot trial, the impact of infusion duration and body size metrics on serum lidocaine concentrations was examined with regression models in 48 women undergoing breast cancer surgery. Lidocaine was delivered as an intravenous bolus (1.5 mg/kg) and infusion (2 mg/kg per h) intraoperatively, followed by a 12-h subcutaneous infusion (1...

The opioids have been used for more than a thousand years and are not only the most widely prescribed drugs for moderate to severe pain and acute pain, but also the preferred drugs. However, their non-analgesic effects, especially respiratory depression and potential addiction, are important factors that plague the safety of clinical use and are an urgent problem for pharmacological researchers to address. Current research on analgesic drugs has evolved into different directions: de-opioidization; application of pharmacogenomics to individualize the use of opioids; development of new opioids with less adverse effects...

Following the contraindication of codeine use in children, increasing use of tramadol has been observed in pain management protocols. However, tramadol's pharmacokinetics (PK) and pharmacodynamics are influenced by cytochrome P450 (CYP)2D6 activity, similarly to codeine. Previous studies in adults have demonstrated a correlation between pupillary response and tramadol PK. Our objective was to evaluate pupillometry as a phenotyping method to assess CYP2D6 activity in children treated with tramadol. We included 41 children (mean age 11 years) receiving a first dose of tramadol (2 mg/kg) in the emergency room (ER) as part of their routine care...

Introduction: As the most distressing complication of sickle cell disease (SCD), pain is marked by considerable heterogenicity. In this study we explored the potential association of alcohol dehydrogenase 7 gene ( ADH7 ) polymorphism rs971074 with sickle cell pain. Methods: We analyzed clinical phenotypes and the rs971074 single-nucleotide polymorphism in ADH7 by MassARRAY-iPlex analysis in a cohort of SCD patients. Results: The synonymous rs971074 was significantly associated with both acute and chronic pain in SCD...

Given the high prevalence of pain in older adults and current trends in opioid prescribing, inclusion of genetic information in risk prediction tools may improve opioid risk assessment. Our objectives were to (1) determine the feasibility of recruiting socioeconomically disadvantaged and racially diverse middle aged and older adult populations for a study seeking to identify risk factors for opioid-related falls and other serious adverse effects and (2) explore potential associations between the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (CIP-RIOSORD) risk class and other patient factors with falls and serious opioid adverse effects...

INTRODUCTION: The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer-related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6-guided opioid prescribing for patients with cancer and reported pilot outcome data. METHODS: Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation-effectiveness clinical trial and randomized to CYP2D6-genotype-guided opioid selection, with clinical recommendations, or usual care...