Optogenetics in Local Anesthesia

Light-Activated, Light-Inactivated Local Anesthesia Optogenetics

• Optogenetics is a technique using light to control genetically modified cells, particularly neurons, in living tissue.
• Optogenetics was first described by Francis Crick in 1999 and was chosen as the "Method of the Year" in 2010.
• Applications of optogenetics include identifying neurons and neural networks, precise temporal control of interventions, and exploring cellular biology and signaling pathways.
• Optogenetics has potential applications in managing cardiac dysrhythmias and has been tested in atrial and ventricular cardiomyocytes in mice.
• Optogenetics has been proposed as a strategy for restoring vision, treating Parkinson's disease, epilepsy, and pain modulation.
• Traditional local anesthetics lack specificity for motor neurons versus sensory neurons and cannot regulate the duration and intensity of anesthesia.
• Researchers have developed a novel local anesthetic, quaternary ammonium–azobenzene–quaternary ammonium (QAQ), which can be switched on and off with different wavelengths of light.
• QAQ exists in two forms, cis and trans, and exposure to 380-nm light converts it to the cis form, which is inactive.
• In its trans form, QAQ blocks many ion channels, while the cis form is inactive, and it can selectively block pain-sensing neurons without affecting motor axons or other sensations.
• QAQ's lack of membrane permeability may limit its clinical usefulness but confers the potential to be a very selective local anesthetic.
• The use of light to control local anesthesia through optogenetics offers the potential for precise and instantaneous turning on and off of anesthesia and targeting specific nerve blocks.
• This technology could potentially allow much finer control of exactly which nerves it blocks, offering targeted and regulated pain relief.

Liposomal Bupivacaine and Proliposomal Ropivacaine in Anesthesia

• Liposomal bupivacaine with DepoFoam technology contains up to 97% bupivacaine packaged in multivesicular lipid spheres.
• It has a slower onset of anesthesia compared to conventional local anesthetics, taking a couple of hours.
• Clinical trials have shown its superiority in pain management and reduced opioid requirement postoperatively in various surgical procedures.
• Liposomal bupivacaine is strictly indicated for postsurgical pain control by infiltration injections around the surgical incision.
• It should not be used for nerve blocks, intra-articular injection, or intraoperative dental local anesthesia.
• Injection of non-bupivacaine local anesthetics at the same site as liposomal bupivacaine may lead to immediate release of bupivacaine from the liposomal spheres.
• The cost of liposomal bupivacaine is significantly higher than traditional bupivacaine, but it provides extended pain control and reduces opioid consumption.
• Animal trials of liposomal bupivacaine have demonstrated prolonged anesthesia without signs of toxicity.
• The shelf life of liposomal local anesthetics is short due to drug leakage, and proliposomal ropivacaine, with a longer shelf life, is being developed.
• Proliposomal ropivacaine has shown extended sensory anesthesia duration and stability at room temperature for more than 24 months.
• The addition of adjuvants such as magnesium to local anesthetics has been shown to increase the duration of pain control and reduce opioid requirements in clinical trials.
• The addition of epinephrine to local anesthetics is routine in dentistry, while magnesium as an adjuvant provides longer anesthesia duration and lowers opioid requirements in some studies.