Dexamethasone as Adjuvant to Bupivacaine Prolongs the Duration of Thermal Antinociception and Prevents Bupivacaine-Induced Rebound Hyperalgesia via Regional Mechanism in a Mouse Sciatic Nerve Block Model

Abstract

BackgroundDexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear.MethodsA mouse sciatic nerve block model was used. The sciatic nerve was injected with 60ul of combinations of various medications, including dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2 days prior to injection, and then continuously for up to 7 days after injection. In addition, the sciatic nerves were harvested at either 2 days or 7 days after injection. Toluidine blue dyeing and immunohistochemistry test were performed to study the short-term and long-term histopathological changes of the sciatic nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg) only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular dexamethasone (0.5mg/kg).ResultsHigh-dose perineural dexamethasone, but not systemic dexamethasone, combined with bupivacaine prolonged the duration of both sensory and motor block of mouse sciatic nerve. There was no significant difference on the onset time of the sciatic nerve block. There was “rebound hyperalgesia” to thermal stimulus after the resolution of plain bupivacaine sciatic nerve block. Interestingly, both low and high dose perineural dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early phase of axon degeneration and Schwann cell response as represented by S-100 expression as well as the percentage of demyelinated axon and nucleus in the plain bupivacaine group compared with the bupivacaine plus dexamethasone groups on post-injection day 2, which resolved on post-injection day 7. Furthermore, we demonstrated that perineural dexamethasone, but not systemic dexamethasone, could prevent axon degeneration and demyelination. There was no significant caspase-dependent apoptosis process in the mouse sciatic nerve among all study groups during our study period.ConclusionsPerineural, not systemic, dexamethasone added to a clinical concentration of bupivacaine may not only prolong the duration of sensory and motor blockade of sciatic nerve, but also prevent the bupivacaine-induced reversible neurotoxicity and short-term “rebound hyperalgesia” after the resolution of nerve block.

Perineural Versus Systemic Dexamethasone in Front-Foot Surgery Under Ankle Block

“…Recent studies do not support any evidence of neural toxicity of dexamethasone when administered perineurally. 26,27 However, these experimental results need to be confirmed before extending the routine use of perineural administration to humans.…”

Perineural versus Intravenous Dexamethasone for Prolongation of Multiple Nerve Blocks for Pain Relief after Total Knee Arthroplasty

“…The use of additional adjuvants were approbated in clinical practice with the aim of prolonging the duration of the single shot PNB, for example, clonidine [50], opioids [51], midazolam [52], ketamine [53] with little effect. DXM was evaluated and appear to be an effective agent for prolonging the duration of PNB in preclinical [23,24], and clinical investigations [13-19, 25, 26]. Most of the previous studies were focused on clarifying the effects of DXM as a local anesthetic adjuvant for brachial plexus block [14,16], but even after a systemic review and meta-analysis the authors concluded that "Perineural administration of dexamethasone with LA prolongs brachial plexus block effects with no observed adverse events.…”

“…The scattered experimental data do not enable their combination into an integral theory explaining this phenomenon [20][21][22][23][24]. The systemic anti-inflammatory action of DXM is well known, and this agent is recommended as a drug commonly used in multimodal pain control methods in knee arthroplasty [55].…”

“…The scattered experimental data that has been published is not sufficient to merge them into an integral theory explaining this phenomenon [20][21][22][23][24].…”

Coadyuvantes farmacológicos con efecto ahorrador de opioides en el periodo perioperatorio

“…Sin embargo, un metanálisis reciente encontró que la administración de dexametasona perineural aumenta la duración del bloqueo en comparación con la administración intravenosa, con un efecto de ahorro de opioides pequeño pero significativo (7,1 mg de equivalentes de morfina oral [intervalo de confianza del 95 %, 0,74-13,5 mg]) a las 24 horas (66). Aunque siguen existiendo preocupaciones teóricas con respecto al potencial de la neurotoxicidad con dexametasona, estudios recientes in vivo en animales a dosis clínicamente relevantes no respaldan esta hipótesis y, de hecho, demuestran un posible efecto neuroprotector (67,68).…”