Flux of morphine, fentanyl, and alfentanil through rabbit arteries in vivo. Evidence supporting a vascular route for redistribution of opioids between the epidural space and the spinal cord.

Abstract

It has been suggested that opioids may move from the epidural space to the spinal cord by way of the spinal radicular arteries. However, there are no data that address this proposed mechanism. The goal of the current study was to determine whether the radicular arterial supply of the spinal cord is a viable route for movement of opioids between the epidural space and spinal cord. The carotid and femoral arteries of anesthetized rabbits were exposed, ligated distally, and cannulated proximal to the ligature. A fluid reservoir was placed around the study vessel and filled with saline buffered to pH = 7.4 or 9.0. The study drug (morphine, fentanyl, or alfentanil) and a radiolabeled tracer were added to the reservoir. Blood was collected as it flowed through the arterial segment bathed by the fluid reservoir and analyzed by scintillation counting to determine how much drug diffused through the arterial wall per minute. Relative flux rates through the carotid artery at pH = 7.4 were alfentanil flux > fentanyl > morphine. Increasing the pH to 9.0 resulted in a significant decrease in fentanyl's flux, but no significant change in alfentanil's or morphine's flux. In addition, the data demonstrate a biphasic relationship between octanol:buffer distribution coefficient and transarterial flux rates. Because the critical step in transporting drug via radicular arteries is diffusion through the radicular artery wall, these data support the idea that drugs may gain direct access to the spinal cord by diffusing into the radicular arteries as they traverse the epidural space en route to the spinal cord.