Perineural administration of dexmedetomidine in combination with bupivacaine enhances sensory and motor blockade in sciatic nerve block without inducing neurotoxicity in rat

Abstract

Background: The current study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage.

Methods: Thirty-one adult Sprague-Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml bupivacaine, 0.5%, and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral extremity, or 0.2 ml dexmedetomidine, 0.005%, and normal saline in the contralateral extremity. Sensory and motor function were assessed by a blinded investigator every 30 min until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 h or 14 days after injection and analyzed for perineural inflammation and nerve damage.

Results: High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 h and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 h than the bupivacaine group when compared with the saline control.

Conclusion: The finding that high-dose dexmedetomidine can safely improve the duration of bupivacaine-induced antinociception after sciatic nerve blockade in rats is an essential first step encouraging future studies in humans. The dose of dexmedetomidine used in this study may exceed the sedative safety threshold in humans and could cause prolonged motor blockade; therefore, future work with clinically relevant doses is necessary.

Figures

Figure 1

Sensory blockade- Dexmedetomidine added to bupivacaine enhanced the duration of sensory blockade in response to lateral paw pinch when compared with bupivacaine alone. Bupivacaine and bupivacaine plus dexmedetomidine showed improved sensory scores when compared with saline and dexmedetomidine. The time course demonstrates the progression from complete sensory blockade (score = 3) to recovery of normal sensory function (score = 0). Time course data for sensory testing were analyzed using a non-parametric model with ordinal logistic regression for repeated measures and generalized estimating equations. Asterisks (*) indicate significant differences for bupivacaine plus dexmedetomidine versus bupivacaine alone at specific times post-injection. † indicates significant differences between dexmedetomidine and saline when compared with bupivacaine plus dexmedetomidine and bupivacaine.

Figure 2

Motor blockade- Dexmedetomidine added to bupivacaine also extended the duration of motor blockade over time when compared to bupivacaine alone. Bupivacaine and bupivacaine plus dexmedetomidine showed improved motor scores when compared with saline and dexmedetomidine. The time course again shows the progression from complete motor blockade (score = 3) to the return of normal motor function (score = 0). Time course data for motor testing were analyzed using a non-parametric model with ordinal logistic regression for repeated measures and generalized estimating equations. Asterisks (*) indicate significant differences for bupivacaine plus dexmedetomidine versus bupivacaine alone at specific times post-injection. † indicates significant differences between dexmedetomidine and saline when compared with bupivacaine plus dexmedetomidine and bupivacaine.

Figure 3

The duration of complete sensory blockade (A) was significantly increased when bupivacaine plus dexmedetomidine (182.0 ± 15.6 min) was compared to bupivacaine (123.8 ± 17.3 min; p

Figure 4

The duration of complete motor blockade (A) was significantly improved when bupivacaine plus dexmedetomidine (158.0 ± 19.1 min) and bupivacaine (101.3 ± 20.7 min) were individually compared with dexmedetomidine (21.4 ± 6.6 min, p

Figure 5

Nerves were sectioned and stained with hemotoxylin and eosin to assess perineural inflammation at 24 hours and 14 days. Nerves in the bupivacaine group had higher inflammation scores at 24 hours when compared with the saline control. Bupivacaine plus dexmedetomidine and dexmedetomidine alone had similar inflammation scores compared with normal saline at 24 hours. At 14 days, nerves in both groups were completely normal with inflammation scores of 0. (A) Inflammation score = 0: The perineural space is void of any significant inflammatory cells. (B) Inflammation score = 1: Focal portions of perineural inflammation involving 5-10% of the sections. (C) Inflammation score = 2: Moderate degree of perineural inflammation. (D) Inflammation score = 3: Severe inflammation is seen with large numbers of lymphocytes surrounding the nerve.