Chapter 37 - Intracerebroventricular Opioid Administration for Chronic Pain

Abstract

This chapter focuses on the use of intracerebroventricular opioid administration for treating chronic pain. The basis of intracerebroventricular (ICV) opioid administration as an alternative local administration of opioids in the cerebrospinal fluid (CSF) rests on preclinical studies of the rat and primate. These studies showed that morphine injection in the spinal CSF induces a powerful analgesia that is of metameric caudal distribution, dose-dependent, stereospecific, and is naloxone-reversible. While ICV administration is effective and reversible, it is more invasive than intrathecal administration as it requires the placement of a catheter through the brain parenchyma and into the lateral ventricles. By using ICV administration, it is possible to use smaller amounts of medication as well as avoid many adverse effects typically experienced with systemic doses. After a drug is infused into the ventricular compartment, minimal amounts of the drug diffuse into the brain parenchyma as the bulk flow of CSF through the ventricles and subarachnoid space is rapid when compared to the relatively slow rate of solute diffusion within the brain itself. Thus, while ICV drug infusion may result in minimal penetration of a drug into the brain parenchyma, the ependymal surface of the central nervous system is exposed to very large concentrations of the drug. Adverse effects of ICV opioids include nausea, drowsiness, somnolence and mental clouding, visual hallucinations, miosis, headache, dizziness, pruritis, diaphoresis, urinary retention, and constipation. Surgical complications related to ICV opioid administration include infection, which may require device explantation. Several other severe complications have been reported that include intracerebral hemorrhage from chronic reservoir use, reservoir leakage, and seizures.