COMPARISON OF ANALGESIC RESPONSES TO INTRATHECAL ANALGESICS ADMINISTERED VIA PE-10 AND 32-GAUGE POLYURETHANE INTRATHECAL CATHETERS IN THE RAT

Abstract

S288 Introduction: Intrathecal catheter implantation is routinely performed for the evaluation of both morphologic as well as pharmacologic effects of drugs. A recent study of the morphologic changes following intrathecal catheter implantation found that a 32 gauge polyurethane catheters (PU-32) produced less inflammatory reaction and reduced encapsulation compared to polyethylene (PE-10) tubing, while latencies to thermal challenges before and after normal saline injections did not differ at 7 days following implantation. [1] This reduction in the inflammatory response to the intrathecal catheter material might allow for a greater period for pharmacologic evaluation of intrathecally administered drugs.. However, no comparison of functional tests to analgesic drug administration via these different catheter systems has been reported. The purpose of this study was to compare analgesic testing following bolus drug analgesic administration via these two catheters over a period of 15 days in rats. Methods: Following IRB approval, 18 male Sprague-Dawley rats (260 +/- 43g) were studied. Catheters were cut from bulk PE-10 (Benton Dickinson, Sparks, MD) or PU-32 (Micor, Allison Park, PA) using a scalpel. To facilitate the bolus intrathecal injections, a 1-cm silastic extension catheter was attached to the proximal end of the PU-32 tubing using silicone adhesive. The coupling between these catheters was tested for leaks prior to insertion. Under pentobarbital anesthesia, the animals had catheters inserted via the cisterna magna and threaded 8.5 cm caudally so that the tip resided at the rostral portion of the lumbar enlargement. The catheters were flushed with saline and sealed with a stainless steel stylet. On the 5th and 15th day after implantation a 3 nmol bolus dose (8[micro sign]L) of morphine was administered followed by an 8[micro sign]L saline flush. Tail flick responses were evaluated at 30 minutes. At the end of the study the animals were perfused with a 10% formalin solution and position and integrity of the catheter examined. Tail flick responses (%MPE) were compared using repeated measures ANOVA. Post hoc testing was done using Bonferroni corrected t-tests. Data are presented as mean +/- SE. Results: Of the 11 PU-32 animals, 6 animals had significant resistance to injection by day 5. Tail flick responses in this group were 16.2 +/- 4.1. The analgesic responses (%MPE) on day 5 in the remaining 5 PU-32 animals was not different from the PE-10 group (Figure 1), but was significantly reduced compared to the PE-10 group on day 15. Examination of the catheter systems revealed material clogging in 60% of the PU-32 catheters.Figure 1Discussion: The findings of this study are somewhat surprising since the reduced inflammation and encapsulation previously reported with the PU-32 did not result in a prolonged period of utility compared to PE-10. The increased resistance to injection was likely a result of clogging of the catheters. These findings suggest that intrathecal PU-32 catheters may not be preferable to PE-10 when intermittent bolus administration is desired over many days.