Glutamate Release and Neurologic Impairment After Intrathecal Administration of Lidocaine and Bupivacaine in the Rat

Cherng, Chen‐Hwan; Wong, Chih‐Shung; Wu, Ching-Tang; Yeh, Chun-Chang

doi:10.1097/aap.0b013e318228cdb0

Cited by 6 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, studies using higher concentrations of lidocaine than those used in the present study have shown that the drug is highly toxic for the nervous tissue [38], and for neuronal cultures [39,40]. In addition, it is well known that 2.5% to 10% lidocaine concentrations induce severe cytotoxic effects even when administered by the intravenous, epidural or intrathecal route [41][42][43]. In vivo studies conducted by Hampl et al [44] showed that 2% lidocaine administered by intrathecal route did not cause histopathologic or structural changes in the spinal cord, while studies performed by Ready et al [45] reported that spinal cord histopathologic changes and neurologic deficits occurred with lidocaine concentrations beyond 8%.…”

Section: Discussionmentioning

confidence: 60%

Effects of an Intraparenchymal Injection of Lidocaine in the Rat Cervical Spinal Cord

et al. 2018

View full text Add to dashboard Cite

Lidocaine effects in the spinal cord have been extensively investigated over the years. Although the intrathecal route is usually used to treat insults occurring in the spinal cord, the local delivery drug via intraparenchymal infusions has gained increasing favor for the treatment of some neurodegenerative disorders. The aim of the present study was to evaluate the behavioral and tissue effects of the intraparenchymal injection of different concentrations of lidocaine into the rat cervical spinal cord. Young male Sprague-Dawley rats were intraparenchymally injected with 0.5%, 1% or 2% lidocaine at the C5 segment of the spinal cord. Other rats were injected with saline solution (sham group). Hot plate test was determined at 0, 1, 2, 3, 7 and 14 post-injection (pi) days. Rats of each experimental group were euthanized either at 1, 2, 3, 7 or 14 pi days. Intact animals were used as controls. Sections of the C5 segment were used for histological, immunohistochemical or immunofluorescence analysis. Injection of 0.5% lidocaine did not affect neuronal counting, did not evoke an inflammatory reaction, nor induce astrocyte activation. Therefore, a concentration of 0.5% lidocaine is suggested to promote anti-inflammatory effects after injury.

show abstract

Section: Discussionmentioning

confidence: 60%

Effects of an Intraparenchymal Injection of Lidocaine in the Rat Cervical Spinal Cord

et al. 2018

View full text Add to dashboard Cite

show abstract

“…It is well established that local anesthetics can cause neurotoxicity (Sakura et al, ). Several mechanisms regarding its neurotoxicity have been proposed including the increase of glutamate release (Cherng et al, ) and the activation of MAPK (Haller et al, ; Lirk et al, ). However, the concentrations of local anesthetics used in the studies cited above are equal to or even higher than the concentrations for local anesthesia.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, Goyagi et al () found that local anesthetics protect against ischemia‐induced brain injury without the alteration of glutamate concentration. Moreover, Cherng et al () reported that local anesthetics may evoke neurotoxicity through the increase of glutamate concentration.…”

Section: Introductionmentioning

confidence: 99%

Local anesthetics inhibit glutamate release from rat cerebral cortex synaptosomes

Lin

Chung

et al. 2013

Synapse

View full text Add to dashboard Cite

Local anesthetics have been widely used for regional anesthesia and the treatment of cardiac arrhythmias. Recent studies have also demonstrated that low-dose systemic local anesthetic infusion has neuroprotective properties. Considering the fact that excessive glutamate release can cause neuronal excitotoxicity, we investigated whether local anesthetics might influence glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Results showed that two commonly used local anesthetics, lidocaine and bupivacaine, exhibited a dose-dependent inhibition of 4-AP-evoked release of glutamate. The effects of lidocaine or bupivacaine on the evoked glutamate release were prevented by the chelation of extracellular Ca²⁺ ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor dl-threo-beta-benzyl-oxyaspartate did not have any effect on the action of lidocaine or bupivacaine. Both lidocaine and bupivacaine reduced the depolarization-induced increase in [Ca²⁺]C but did not alter 4-AP-mediated depolarization. Furthermore, the inhibitory effect of lidocaine or bupivacaine on evoked glutamate release was prevented by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but it was not affected by blocking of the ryanodine receptors or the mitochondrial Na⁺/Ca²⁺ exchange. Inhibition of protein kinase C (PKC) and protein kinase A (PKA) also prevented the action of lidocaine or bupivacaine. These results show that local anesthetics inhibit glutamate release from rat cortical nerve terminals. This effect is linked to a decrease in [Ca²⁺]C caused by Ca²⁺ entry through presynaptic voltage-dependent Ca²⁺ channels and the suppression of the PKA and PKC signaling cascades.

show abstract

“…Behavioral Tests The Basso, Beattie, and Bresnahan (BBB) scale, ranging from 0 (no movement) to 21 (normal movement), was used to assess the locomotor function of the hind limbs as previously described. 14) BBB scoring was performed on a mat four times for each rat on days 1-4. Each test was conducted for 5 min by two researchers with no knowledge of the experimental groups.…”

Section: Animals and Experimental Protocolmentioning

confidence: 99%

Dexmedetomidine Reduces the Lidocaine-Induced Neurotoxicity by Inhibiting Inflammasome Activation and Reducing Pyroptosis in Rats

Ding

Cao

et al. 2021

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Local anesthetic toxicity is closely related to neuronal death and activation of the inflammatory response. Dexmedetomidine (Dex) is an adrenergic α2 receptor agonist that can reduce the neurotoxicity induced by lidocaine. It also has anti-inflammatory effects. However, the mechanism underlying the neuroprotective effects of Dex against lidocaine-induced toxicity remains to be defined. We hypothesized that Dex exerts its neural protective effect through inhibiting inflammasome activation and through anti-pyroptosis effects against local anesthetic-induced nerve injury. In a rat model of lidocaine-induced spinal cord injury, we studied the protective effect of Dex on lidocaine-induced changes in spinal cord function, inflammasome formation and pyroptosis, pro-inflammatory cytokine expression, and protein kinase C (PKC)-δ phosphorylation. Dex reduced lidocaine-induced neurotoxicity and inhibited PKC-δ phosphorylation in the spinal cord of rats. Furthermore, Dex inhibited pyroptosis and inflammasome formation (caspase-1, NLRP3, and apoptosis-associated speck-like protein (ASC)). Finally, Dex attenuated interleukin (IL)-1β and IL-18 expression, as well as microglia response. In conclusion, Dex can reduce the severity of lidocaine-induced spinal cord injury in rats by inhibiting priming and inflammasome activation and reducing pyroptosis via PKC-δ phosphorylation.

show abstract

Glutamate Release and Neurologic Impairment After Intrathecal Administration of Lidocaine and Bupivacaine in the Rat

Cited by 6 publications

References 27 publications

Effects of an Intraparenchymal Injection of Lidocaine in the Rat Cervical Spinal Cord

Effects of an Intraparenchymal Injection of Lidocaine in the Rat Cervical Spinal Cord

Local anesthetics inhibit glutamate release from rat cerebral cortex synaptosomes

Dexmedetomidine Reduces the Lidocaine-Induced Neurotoxicity by Inhibiting Inflammasome Activation and Reducing Pyroptosis in Rats

Contact Info

Product

Resources

About