Pharmacogenetics in Pain Treatment

Pain is an unpleasant feeling usually resulting from tissue damage that can persist along weeks, months, or even years after the injury, turning into pathological chronic pain, the leading cause of disability. Currently, pharmacology interventions are usually the first-line therapy but there is a highly variable analgesic drug response. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual analgesic response opening doors to precision medicine. PGx analyze the way in which the presence of variations in the DNA sequence (single-nucleotide polymorphisms, SNPs) could be responsible for portions of the population reaching different levels of pain relief (phenotype) due to gene interference in the drug mechanism of action (pharmacodynamics) and/or its concentration at the place of action (pharmacokinetics). SNPs in the cytochrome P450 enzymes genes (CYP2D6) influence metabolism of codeine, tramadol, hydrocodone, oxycodone, and tricyclic antidepressants. Blood concentrations of some NSAIDs depend on CYP2C9 and/or CYP2C8 activity. Additional candidate genes encode for opioid receptors, transporters, and other molecules important for pharmacotherapy in pain management. However, PGx studies are often contradictory, slowing the uptake of this information. This is likely due, in large part, to a lack of robust evidence demonstrating clinical utility and to its polygenic response modulated by other exogenous or epigenetics factors. Novel therapies, including targeting of epigenetic changes and gene therapy-based approaches, broaden future options to improve understanding of pain and the treatment of people who suffer it.