Intracerebroventricular opioids for intractable pain

Abstract

When pain is refractory to systemic opioid and non-opioid analgesic therapy and palliative chemoradiation or ablative or stimulant neurosurgical procedures are not possible, palliative treatment becomes limited, particularly if the patient wishes to be at home at the end of life. Intracerebroventricular (ICV) infusion of morphine in the home setting might be presented as an option. The present article reviews the basic and clinical evidence of the efficacy and safety of ICV administration of opioids. Information was gathered from various bibliographic sources, including PubMed and others, and summarized and evaluated to assess the efficacy and safety of ICV opioids for pain relief. Results from ICV infusion of morphine into terminally ill patients refractory to other pain treatments have been reported since the early 1980s. Good efficacy has been achieved for the vast majority of patients, without serious development of analgesic tolerance. There have also been a low incidence of adverse effects, such as constipation and respiratory depression, and a significant retention of alertness associated with this route of administration. Intracerebroventricular infusion of opioid analgesics thus appears to be a safe and effective therapy for the palliative treatment of refractory pain.

Intracerebroventricular Delivery as a Safe, Long-Term Route of Drug Administration

“…The ICV route of administration has been used extensively in clinical settings for more than half a century 2 and has become an established and routine CNS delivery method for long treatment durations. Our results indicate that the ICV route of administration appears to be a safe and well-tolerated long-term method of drug delivery in both pediatric and adult patients.…”

“…This route of administration, also referred to as intraventricular administration, has been used for several decades to provide treatments for pediatric and adult patients who suffer from a broad range of diseases, including infectious meningitis, intractable pain, and various types of cancer. [1][2][3][4][5] In addition to the ICV route, intrathecal delivery methods include single or repeated intrathecal lumbar (IT-L) injections, in which agents are directly administered into the cerebrospinal fluid (CSF) by puncturing the membranes surrounding the spinal cord (Fig 1). Intrathecal routes of administration allow therapies to bypass the bloodebrain barrier (BBB) and are commonly used to treat a variety of diseases in pediatric and adult patients.…”

Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

“…The most direct route to the CNS is to inject the drug into the intraventricular, intracavitary, or interstitial system. For example, intracerebroventricular (ICV) administration is considered as an intrathecal delivery via an ICV port implanted under the scalp of the patient and is used for treating various types of CNS diseases, such as infections [231,232], chronic pain [233,234], and types of brain cancer [235]. This local delivery ensures high drug concentrations in the CNS while the peripheral exposure is minimal.…”

Neurobiological studies of chronic pain and analgesia: Rationale and refinements

“…For continuous infusion of compounds in mice (Lenard and Roerig, 2005) or rats (Vonhof et al, 2003) cannula implantation via surgical procedures is necessary. The use of the ICV route of administration clinically is very limited; when accessed it is typically for delivery of opioid medication for palliative care (Raffa and Pergolizzi, 2012) in cases where systemically or spinally delivered opioids have become no longer effective. One case report (Lorenz et al, 2002) illustrated the effectiveness of substituting clonidine for morphine when ICV morphine became ineffective due to tolerance and/or disease progression.…”