While local anesthetics are generally safe and well-tolerated, they can occasionally cause adverse effects that vary in severity. Local anesthetics can induce toxicity at two distinct levels. They can either produce local effects through direct contact with the neural elements or be absorbed into the bloodstream from the injection site, leading to systemic effects.

Once absorbed into the systemic circulation, local anesthetics can affect the organs that depend on the functioning of sodium channels. The central nervous system is the most affected, followed by the cardiovascular system. Low systemic concentrations of local anesthetics can induce symptoms such as dizziness, auditory and visual disturbances. Higher systemic concentrations of local anesthetics can lead to tremors, seizures, and in severe cases, central nervous system depression or coma. Some individuals may develop allergic reactions to local anesthetics, leading to symptoms such as rash, itching, hives, or even anaphylaxis in severe cases. In rare cases, local anesthetics can cause tissue necrosis if they inadvertently infiltrate blood vessels or are administered in excessive amounts.

The mechanism of neurotoxic effects of local anesthetics has been extensively studied using cell culture, ex vivo, and in vivo models. The potential factors contributing to neurotoxicity are excessive or prolonged sodium channel blockade, disruption of the cytoskeleton of neurons, neuronal membrane damage, disruption of axonal transport, and apoptosis. Furthermore, local anesthetics can cause transient neurological symptoms, like dysesthesia or transient pain syndrome, which can occur when administered spinally or epidurally. These symptoms can cause mild to severe pain, sometimes surpassing the pain induced by surgical procedures.