Pain Management Pharmacogenetics (PGX) Gene Variation Panel

Diseases Associated

Acute pain • Chronic pain • Lumbar spondylolysis • Opioid dependence • Ankylosing spondylitis • Attention deficit hyperactivity disorder • Epilepsy • Major depressive disorder (Depression) • Osteoarthritis (Osteoarthrosis) • Psychosis • Rheumatoid arthritis • Schizophrenia • Seizure disorder

Test Overview

One of the challenges in pain management has always been the varying degrees of sensitivity for patients who need drug administration for pain alleviation. The sensitivity of pain management drugs relies on various factors including the metabolic status, route of administration, and patient genomics. These factors have been shown to have a significant influence on patients’ reactivity to medication. Several polymorphisms and mutations have been identified through years of extensive genetic research that are associated with either insensitivity or hypersensitivity for individuals needing a particular pain management drug regimen. Most often, these genetic variations are associated with poor drug response and to a lesser extent with adverse reactions.

Metabolizing of drugs for pain management or simply pain medications occurs via cytochromes produced in the liver. Because of the interindividual variability in metabolizing pain medications, the dosing of a certain medication can produce different results for patients. Part of this variability can be attributed to genetic factors that affect the activity of cytochromes the rate of metabolizing medication, and ultimately the efficacy of the prescribed medication. In addition, transportation and utilization of these drugs depends on transporting proteins and receptors that are responsible for internalizing the drug. Thus, using pharmacogenetic (PGx) testing determines a patient’s genetic makeup, as it pertains to drug metabolism, transportation, and utilization, and offers healthcare providers insight into a patient’s predicted response to a prescribed medication, and improve the precision of treatment.

Pain management involves the application of various drugs with different targets and mechanisms of action. The commonly administered drugs are found in multiple categories, which include opioids, NSAIDs, acetaminophen, anti-depressants, and anti-epileptics. These drugs have different mechanisms of action and offer different therapeutic effects for patients. For instance, opioids work by binding to specific opioid receptors and block release of neurotransmitters that relay pain signals throughout the nervous system. Genetic variations in the formation of opioid receptors could either inhibit opioid binding and induce insensitivity or promote extensive binding and lead to hypersensitive actions. Likewise, mutations in drug-metabolizing genes as in the cytochrome P450 enzyme family may lead to poor drug metabolism. All in all, genomics influences the drug’s pharmacokinetics and pharmacodynamics.

Incorporating all possible genetic variations that influence pain management therapy into a PGx panel testing offers an advantage over individual mutation or variant analysis. PGx panel testing utilizes molecular methods, polymerase chain reaction (PCR), and next-generation sequencing (NGS), to detect variants and polymorphisms in all target genes incorporated. Receptor gene OPRM1, metabolizing genes COMT, CYP3A4, CYP2D6, CYP2C9, UGT2B7, transporter genes ABCB1, ABCC2, ABCC3, SLC1A2, SLC1B3, and human leukocyte antigen genes HLA-B*1502, HLA-B*3101, HLA-B*1502, HLA-B*3801, and HLA-DQ81 are included in the PGx panel. Most importantly, testing for these genes via the PGx panel allows pre-information on drug sensitivity and rules out the trial and error approach in pain management.   

Clinical Utility:

• Pain management therapy selection
• Therapy monitoring and disease management