Pain and the pharmacogenetics at the fuzzy border between pain physiopathology and pain treatment

Abstract

Nociceptive pain is time limited and severe nociceptive pain normally responds well to treatment with opioids, On the contrary, neuropatic pain is frequently chronic, and tends to have a less robust response to treatment with opioids. The unsolved problem of insufficient pain treatment at clinical level, including both wanted analgesic effects and unwanted side effects, is a stimulus to expand the knowledge on the physiophatology of pain and on the involved molecular mechanisms. In particular, it is important not only to better understand the molecular mechanisms associated to drugs effects but also to characterize the genetic traits underlying pharmacokinetic (PK) and pharmacodynamic (PD) mechanisms related to drugs. Literature analysis reveals that there are interesting genetic polymorphisms that are associated either to the sensitivity to pain and to PD response to drugs, or to the metabolic and excretion pathways. Pharmacogenetics/pharmacogenomics holds the promise that drugs might in the next future be tailor-made for individuals and adapted to each person's own genetic background. Collected information, allowing to design combined therapies and to dissect analgesic from addictive properties of opioids within a given patient, will also contribute to contrast the persisting opiophobia in medical practice.