Perineural Dexmedetomidine Added to Ropivacaine for Sciatic Nerve Block in Rats Prolongs the Duration of Analgesia by Blocking the Hyperpolarization-activated Cation Current

Abstract

Background The present study was designed to test the hypothesis that the increased duration of analgesia caused by adding dexmedetomidine to local anesthetic results from blockade of the hyperpolarization-activated cation (Ih)current. Methods In this randomized, blinded, controlled study, the analgesic effects of peripheral nerve blocks using 0.5% ropivacaine alone or 0.5% ropivacaine plus dexmedetomidine (34 μM or 6 μg/kg) were assessed with or without the pretreatment of α1- and α2-adrenoceptor antagonists (prazosin and idazoxan, respectively) and antagonists and agonists of the Ih current (ZD 7288 and forskolin, respectively). Sciatic nerve blocks were performed, and analgesia was measured by paw withdrawal latency to a thermal stimulus every 30 min for 300 min post-block. Results The analgesic effect of dexmedetomidine added to ropivacaine was not reversed by either prazosin or idazoxan. There were no additive or attenuated effects from the pretreatment with ZD 7288 (Ih current) when compared with dexmedetomidine added to ropivacaine. When forskolin was administered as a pretreatment to ropivacaine plus dexmedetomidine, there were statistically significant reductions in duration of analgesia at time points 90–180 min (p < 0.0001 for each individual comparison). The duration of blockade for the forskolin (768 μM) followed by ropivacaine plus dexmedetomidine group mirrored the pattern of the ropivacaine alone group, thereby implying a reversal effect. Conclusion Dexmedetomidine added to ropivacaine caused approximately a 175% increase in the duration of analgesia, which was reversed by pretreatment with an Ih current enhancer. The analgesic effect of dexmedetomidine was not reversed by an ∝2-adrenoceptor antagonist.

Dexmedetomidine as an Adjuvant to Levobupivacaine in Ultrasound Guided Supraclavicular Brachial Plexus Block

“…Kousugi et al in their study found high concentrations of dexmedetomidine inhibit compound action potentials in frog sciatic nerves without α-2 adrenorecptors activation in a concentration dependent manner and reversibly. [23,24,25] The efficacy of perineural dexmedetomidine for analgesia has been established. This effect is dose dependent and the effect is peripheral (not caused by centrally mediated or systemic analgesia).…”

Efeitos antinociceptivos, analgésicos e histopatológicos de dexmedetomidina e bupivacaína intratecal em rato

“…Ishii and colleagues reported that dexmedetomidine induced activation of K + -channels through α 2A -and α 2C -adrenoceptors results in hyperpolarization of substantia gelatinosa neurons 15 . Similarly, Brummett and colleagues reported that dexmedetomidine's antinociceptive action depends on inhibiting the build up of excitation via hyperpolarization-activated cation current (I h ) and is reversed by I h agonist forskolin 17 . Among spinal catheterization methods, sacral approach is mainly suited for epidural drug administration and lumbar approach carries the risks of bone damage and infl ammation due to fi xatives.…”

Dexmedetomidine vs. Magnesium Sulphate as an Adjuvant to Rocuronium Bromide, and Local Anaesthetic Mixture in Peribulbar Anaesthesia for Viteroretinal Surgery

“…It produces a dose dependent sedation and analgesia, recently, Dexmedetomidine has been used as adjuvant to LA drugs in peripheral nerve block and eye block [41] this action is mainly due to blocking the hyperpolarization-activated cation current [42].…”