Temporomandibular disorders (TMDs) are prevalent conditions affecting the temporomandibular joint (TMJ), masticatory muscles, and associated structures, leading to pain, restricted movement, and joint noises. These disorders are multifactorial in origin, involving structural, functional, and psychological components. This review delves into the neurophysiological mechanisms of pain perception in TMDs, focusing on peripheral and central processes, including the role of neural plasticity in chronic pain. Peripheral mechanisms involve nociceptors in the TMJ, activated by inflammatory mediators, mechanical stress, and tissue damage, leading to pain. Peripheral sensitization, driven by factors such as cytokines and neuropeptides, enhances nociceptor sensitivity, contributing to chronic pain states. The trigeminal nerve is pivotal in transmitting nociceptive information to the central nervous system (CNS), with C-fibers and A-delta fibers involved in pain perception. Central sensitization, a hallmark of chronic pain in TMDs, involves neuroplastic changes in the CNS, including wind-up and long-term potentiation (LTP), enhancing pain perception and facilitating pain persistence. Neuroplasticity, both central and peripheral, plays a critical role in the development of chronic pain. Central plasticity includes synaptic changes and alterations in brain connectivity, which were observed in functional imaging studies of TMD patients. Peripheral plasticity involves the upregulation of ion channels and neurotransmitters, sustaining pain signals. Additionally, neuroimmune interactions between microglia, astrocytes, and pain pathways are integral to central sensitization. Understanding these mechanisms is crucial for developing effective treatments targeting both peripheral and central pain processes. Emerging therapies, including transient receptor potential (TRP) channel blockers and neuroimmune modulators, offer new avenues for managing TMD pain, emphasizing the need for a multifaceted treatment approach.