Orthodontic treatment has demonstrated efficacy in enhancing dental health and rectifying tooth misalignments. Nevertheless, patients experience substantial discomfort and distress. Advancements in orthodontic technology and treatment procedures have led to a decrease in orthodontic discomfort. Orthodontic discomfort refers to the inflammation that occurs due to the obstruction of blood vessels by orthodontic force. This leads to inflammatory responses, which encompass alterations in blood vessels, recruitment of inflammatory and immune cells, and heightened sensitivity of nerves along with the release of chemicals that promote inflammation. The body's inherent analgesic systems ultimately regulate the inflammatory response, thereby diminishing pain. Orthodontic pain signals are transmitted by three-order neurons, beginning with the trigeminal neuron located in the trigeminal ganglia. The signals subsequently arrive at the trigeminal nucleus caudalis located in the medulla oblongata, as well as the ventroposterior nucleus in the thalamus, where the sensation of pain is perceived. The processing of orthodontic pain involves the interplay of emotion, cognition, and memory in many parts of the brain. The structures encompassed in this list are the insular cortex, amygdala, hippocampus, locus coeruleus, and hypothalamus. The inherent analgesic neuronal pathway of the periaqueductal gray and dorsal raphe regions alleviates orthodontic discomfort. Various techniques are employed to manage orthodontic discomfort. These therapies encompass pharmacological, mechanical, behavioral, and low-level laser treatments. Nonsteroidal anti-inflammatory medicines (NSAIDs) alleviate pain, but their impact on tooth movement remains uncertain. Additional research is required to establish the effectiveness of alternative modalities. Gene therapy provides a new, practical, and hopeful approach to treating orthodontic pain. This article explores new advancements and techniques that have enhanced the level of comfort experienced by orthodontic patients.