The protective effect of dexmedetomidine on bupivacaine-induced sciatic nerve inflammation is mediated by mast cells

Abstract

Purpose: This study was designed to assess the correlation between the neuroprotective effect of dexmedetomidine and oxidative stress, neural inflammation and mast cell stability in rats with bupivacaine-induced sciatic nerve toxicity. Methods: Forty adult Wistar Albino rats, eight rats per group, were used. Saline (0.3 ml of 0.9%), dexmedetomidine (20 µg/kg), 0.5% bupivacaine or 0.5% bupivacaine+dexmedetomidine (20 µg/kg) was injected into the sciatic nerve. A control group of rats received no injection. Fourteen days after injection, the sciatic nerves were harvested and total oxidant status, total anti-oxidant status, paraoxonase-1, galectin-3 and matrix metalloproteinase 2 and 9 levels were measured in the sciatic nerves. In addition, the presence and status of inflammation, edema, and mast cells were evaluated histopathologically. Results: The combination of dexmedetomidine and bupivacaine alleviated oxidative stress. In addition, it decreased matrix metalloproteinase 9 and galectin-3 levels and increased matrix metalloproteinase 2 levels. Moreover, it stabilized recruited mast cells at the injury site; however, it did not significantly decrease inflammation or edema. Conclusion: Dexmedetomidine may ameliorate bupivacaine-induced neurotoxicity by modulating mast cell degranulation. The neuroprotective effect of dexmedetomidine may make it a suitable adjuvant agent to local anesthetics in peripheral nerve blocks.

Regional anaesthesia, diabetic neuropathy, and dexmedetomidine: a neurotoxic combination?

“…The likely mechanism was stabilisation of mast cells at the injury site. 15 These data build on previous research of clonidine's a 2A -mediated neuroprotective effects in rat nerve injury models. 16 This has led to dexmedetomidine being characterised by some as the most promising of the adjuvants currently available.…”

The newer aspect of dexmedetomidine use in dentistry: As an additive to local anesthesia, initial experience, and review of literature

“…However, in animal models of spinal anesthesia and sciatic nerve block, dexmedetomidine did not show toxicity and was potentially neuroprotective when combined with lignocaine and bupivacaine. [2021] The published data support the efficacy of dexmedetomidine for peripheral nerve block prolongation of approximately 200 min at doses around 1 mcg/kg, and it appears to be a viable option as an additive to local anesthetics, especially where bradycardia and hypotension is an issue.…”

Perineural Dexmedetomidine Attenuates Inflammation in Rat Sciatic Nerve via the NF-κB Pathway

“…Recent studies found that dexmedetomidine has an anti-inflammatory effect by reducing the serum levels of inflammatory cytokines, however, the upstream mechanism is still unknown [4–6]. In the present study, we used a surgical procedure and perineural injection to induce a background inflammatory response (e.g., increasing IL-6 and TNF-α levels) in sciatic nerve tissue to investigate the anti-inflammatory effect of perineural administration of dexmedetomidine and the underlying mechanism.…”

“…Recent studies found that dexmedetomidine has an anti-inflammatory effect through reducing the serum levels of inflammatory factors, which may extend its application in the clinic [4–6]. However, the upstream mechanism by which dexmedetomidine reduces inflammatory factors levels remains largely unknown.…”