Pharmacologist Dr Andrea Kliewer of Jena University Hospital has clarified essential mechanisms for the development of tolerance to opioids such as fentanyl and morphine. (Photo: Michael Szab├│/UKJ )

Through genetic changes to the opioid receptor in mice, pharmacologists at Jena University Hospital have succeeded in almost completely suppressing the development of opioid tolerance. The pain-relieving effect actually improved and continued even when the drug was administered for longer periods. However, adverse effects such as respiratory depression and constipation, as well as withdrawal symptoms, were unchanged. The study, now published in Nature Communications, suggests that the development of opioid tolerance is mediated by phosphorylation and desensitisation of the opioid receptor. These findings can be used in developing improved opioids.