Local anesthetics: New insights into risks and benefits

Conventional local anesthetics in contemporary use block the voltage-gated sodium channel by binding to a specific site on the inner facet of the channel pore. Only little fractions of local anaesthetic are thought to participate in nerve blockade, the rest is absorbed into surrounding tissues or the systemic circulation.
The first major outcome of this thesis is that clinically relevant concentrations of local anaesthetics exert demethylating effects on specific breast cancer cells, and seem to enhance demethylating properties of prototype epigenetic chemotherapeutic, 5-aza, in an additive fashion. These effects could be of substantial importance in perioperative medicine, with focus on tumour surgery and pain prevention.
The second main topic of this thesis was nerve injury and regional anesthesia in healthy and diabetic neuropathic nerves. In a large animal model of regional anesthesia, experimental needle trauma as well as intraneural injection of small volumes of saline resulted in severely impaired nerve function, arguing against intraneural injection as proposed by some authors. In another line of evidence, experimental sciatic nerve block in a rodent model of Type II diabetes lasted substantially longer in late diabetic neuropathy as compared to healthy animals. However, our results do not support the hypothesis that nerve block in diabetic patients increases nerve injury after peripheral nerve block.
The use of regional anaesthesia should always be preceded by a weighing of potential risks and proven benefits. Regional anaesthesia continues to play a major role in perioperative medicine, but its role keeps getting more defined and less noncommittal.