Local Anesthetics Inhibit Ca-ATPase in Masticatory Muscles

Abstract

Local anesthetics have myotoxic effects and inhibit Ca-ATPase activity and Ca transport in skeletal muscles. Such effects have not been fully elucidated in masticatory muscles. We tested the hypothesis that local anesthetics increase myoplasmic calcium in masticatory muscles by inhibiting Ca-ATPase at a concentration similar to that of dental cartridges. The effects of lidocaine and bupivacaine on Ca-ATPase from rabbit masseter and medial pterygoid muscles were tested with radioisotopic and colorimetric methods. Bupivacaine had an action similar to that of lidocaine on Ca-ATPase activity, but less effect on calcium transport. The pre-exposure of the membranes to the anesthetics enhanced the Ca-ATPase activity in the absence of calcium ionophore, supporting their permeabilizing effect. The results demonstrate that amide-type anesthetics do not inhibit calcium binding, but do reduce calcium transport and enzyme phosphorylation by ATP, and suggest that the myoplasmic calcium increase induced by lidocaine and bupivacaine might promote masticatory muscle contraction and eventual rigidity.

In vitro exposure of human fibroblasts to local anaesthetics impairs cell growth

“…Other studies have suggested an inhibition of Ca 2+ reuptake into the sarcoplasmic reticulum, possibly regulated by Ca 2+ ATPase activity [34,36]. Besides dysregulated intracellular Ca 2+ , the involvement of ROS production is another possible mechanism of LA-induced cell death [37,38].…”

“…It is postulated in myocytes that LA induce Ca 2+ release from the sarcoplasmic reticulum by interaction with ryanodine receptors [34,35]. Other studies have suggested an inhibition of Ca 2+ reuptake into the sarcoplasmic reticulum, possibly regulated by Ca 2+ ATPase activity [34,36]. Besides dysregulated intracellular Ca 2+ , the involvement of ROS production is another possible mechanism of LA‐induced cell death [37,38].…”

Investigating the Cytotoxic and Anti-Bacterial Activity of Commercially Available Local Anesthetics: An In-Vitro Analysis

“…12,24 Secondly, muscular stiffness is also linked to the myotoxic effects of anesthetics resulting in degenerative changes in masseter and medial pterygoid. 12,25 Another usual post-operative clinical complication, following a palatine block, is the occurrence of palatal ulceration or tissue necrosis, which is caused by anesthetic toxicity or high concentration of vasoconstrictors. 26 Two limitations in implementing this study design were the use of the same anesthetic agent in the same concentration along with epinephrine, thus higher concentrations of lidocaine could not be evaluated neither estimation of their individual toxic effect was possible.…”

Local anaesthetic-induced myotoxicity in regional anaesthesia: a systematic review and empirical analysis

“…15,30,33e38,41,43 These mechanisms are thought to be related to LA interference with ATP phosphorylation. 37,41,43 A surge in myoblastic apoptosis is the sequela of LA exposure. 1,19e23,25e29 Apoptosis is triggered by increased Back muscles, 37 back leg muscles, 43 breast muscle, 28 C2C12 cell line, 18e23,25,26 oesophageal muscle, 24 extensor digitorum longus muscle, 1,24,35,36 first lumbrical of foot muscle, 27 flexor digitorum brevis muscle, 24 hind leg muscles 15,32,33,42 masseter muscle, 34,37,41 medial pterygoid, 37,38,41 psoas muscle 40 quadriceps muscle, 29 skeletal muscle, 13,30,31 soleus muscle, 1,24 temporalis muscle, 39 tibialis anterior muscle 1 Humans, 13,29 mice, 1,18e26,35,36 quail, 28 rats, 27 pigs, 42 rabbits 15,30e34,37e41,43 Articaine, 38 benzocaine, 32 bupivacaine, 1,13,18e21,23e29,34,35,41e43 bupivacaine S and R enantiomers, 35,36 bupivacaine with caffeine, 1 bupivacaine with dantrolene...…”