Opioïds

Painful procedure usually requires analgesia and sedation, especially when it involves new born. Commonly, these therapies implicate the use of opioids. Inter-individual differences in sensitivity to pain and opioid analgesics are well described in adults and might be relevant also in the neonatal population for whom this pain treatment happens during a vulnerable and critical period of central nervous system development. Genetic variants located in genes implicated in the opioid response pathway might explain the various phenotypes related to pain susceptibility and response to opioid therapy. As a result, a multimodal balanced approach aiming at pain relief without the use of unnecessary harmful drugs and/or excessive dosage is recommended but present knowledge appears as rather limited. In the past, our group has achieved some promising advancements in that particular field by showing that two particular genetic variants are likely to predispose preterm newborns to diminished opioid-induced pain relief. In parallel, in another investigation, we have highlighted a significant association between a variant located in a gene involved in the PK pathway of morphine and the production of its metabolites giving new leads to explain individual differences in treatment effectiveness and giving rationale to fine-tune the analgesic therapeutic arsenal with might be inadequate or too aggressive for infants. In 2015, we have confirmed that pharmacogenetics has a role to play in the management of pain and that we are not all equal regards to pain medication. Indeed, in collaboration with the Erasmus MC (Rotterdam), in newborns, we have shown that CYP2D6 as well as OCT1 genotypes contribute independently to the variability observed in the production of the therapeutically active metabolite of tramadol o-desmethyltramadol. This is particularly relevant as, in this frail and developing population, pain medication can be armful if not correctly dosed. Hopefully, if these observations are confirmed, it is possible that CYP2D6 and OCT1 genotypes might serve to set up new clinical guidelines in determining the optimal dose for the newborns.
In addition, in collaboration with Lund Children’s Hospital (Sweden) and Erasmus MC (Rotterdam), we have investigated how genetics can explain the variability observed in pain relief which was scored on a validated scale after treatment with opioids (Remifentanyl or morphine) among preterm infants needing intubation. We have shown that some infants needed more time to achieve a pain score indicating no pain and this could be partly explain by their genetic make-up. We have pinpoint two genetic variants located in genes involved in the natural modulation of pain (COMT and KCNJ6).