Super analgesia of intrathecal morphine may be related to ABCB1 ( MDR1) gene polymorphism

Abstract

Intrathecal morphine provides superior analgesia and minimizes side effects with ~1/300th of the oral dose necessary to achieve this effect. The conversion ratios from oral route to intrathecal route vary greatly among individuals, and this may be related with polymorphisms of the ATP-binding cassette B1 ( ABCB1)/ multiple drug resistance 1 ( MDR1) gene encoding the transporter P-glycoprotein in the blood–brain barrier. In the case presented herein, a patient with cancer pain for over 3 months was treated with oxycodone hydrochloride prolonged-release tablets (Oxycontin) and morphine hydrochloride tablets for breakthrough pain. The patient was admitted due to intolerable adverse effects of Oxycontin. During this admission, he was implanted with an intrathecal morphine pump which can deliver morphine into the cerebrospinal fluid. To our surprise, intrathecal morphine at a dose of ~1/540th of oral morphine equivalent dose produced complete analgesia. Our finding revealed homogenous CC at position 3435 (C3435T) in the ABCB1/ MDR1 gene in this patient, which encodes P-glycoprotein with good efflux pump functionality. As intrathecal morphine bypasses the blood–brain barrier that oral medications have to pass through, the good pump functionality may have contributed to the super analgesia of intrathecal morphine in this case. Genetic analysis of ABCB1/ MDR1 gene polymorphisms can be useful for personalized pain management in patients with intrathecal morphine pump.