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Chapter 342the medulla. The postsynaptic neuron brings the stimulus to the thalamus. At the synapse, approaching neural signals are transferred to the cerebral cortex, where they are analyzed and converted into an emotional response, causing both pain and protective reflexes.16,17 LLLT is thought to interrupt this painassociated neurosensory pathway; however, the exact mechanism remains elusive. LLLT may enhance the release of endorphins, which bind to the opiate receptors of the nociceptors and, thereby, block the receptors and the pain stimulus pathway.16 Another hypothesis is that LLLT increases the activity of acetylcholine esterase (an enzyme that breaks down the neurotransmitter acetylcholine at the synaptic cleft), and the increased acetylcholine neutralization blocks the pain stimulus.16 Data also indicate that promoting collagen formation and tensile strength has positive effects on postoperative pain control and enhancement of tissue repair.17,18 A prospective single-blind clinical trial recently demonstrated that a gallium-aluminum-arsenide laser did not decrease pain perception due to needle insertion into the maxillary buccal mucosa.19We hypothesized that patients undergoing local anesthesia or mandibular block procedures would benefit from LLLT performed prior to injection, with regards to reduced pain and anxiety. To test this hypothesis, we conducted a single-center double-blind randomized controlled trial (RCT) in a cohort of healthy patients undergoing either maxillary or mandibular third molar extractions. To objectively evaluate the results, we collected data using both physiological and questionnaire-based sources. Materials and methodsThis study was performed in accordance with the principles established in the Declaration of Helsinki (Fortaleza, October 2013). The guidelines and procedures for this investigation were reviewed and approved by the Medical Ethical Committee of the Academic Medical Center of the University of Amsterdam (Reg. Nr. NL46371.018.14). Each participant received a detailed explanation of the study procedures and gave their signed informed consent.