Trigeminal neuralgia: peripheral and central mechanisms

Abstract

BACKGROUND AND OBJECTIVES: Trigeminal neuralgia is one of the most common neuropathic pains that compromise head and neck. It manifests as shock or burning pain normally evoked by non-noxious facial stimulations. Its etiopathology is not totally understood, but it is known that different mechanisms contribute to the establishment and maintenance of pain. This study aimed to address current contexts of epidemiology, diagnosis, management and pathophysiological mechanisms underlying trigeminal neuralgia in peripheral and central nervous systems. CONTENTS: Inflammation and release of inflammatory mediators, neuropeptides and neurotrophic factors, as well as degenerative changes of nervous fibers caused by direct nervous injury are relevant peripheral mechanisms which lead to altered sensitivity of nociceptive neurons, development of spontaneous and exacerbated activity, allodynia and hyperalgesia. Among central mechanisms, exacerbated activation of central nociceptive neurons, neuroplasticity, changes in electrophysiological properties and neuronal hyperexcitability, in addition to changes in modulatory pain controls, lead to pain establishment and maintenance. CONCLUSION: Several mechanisms are involved in neuropathic pains, both in peripheral and central levels, although specific trigeminal neuralgia events are not totally described. Studies concerning its specific neurobiology are needed to understand functional and behavioral changes, which can contribute to trigeminal neuralgia clinical management and treatment.

Antagonism of Transient Receptor Potential Ankyrin Type-1 Channels as a Potential Target for the Treatment of Trigeminal Neuropathic Pain: Study in an Animal Model

“…After nerve injury, an inflammatory process leads to the release of many pro-inflammatory mediators, which participate in peripheral sensitization, promoting an excessive release of neurotransmitters [ 94 ]. Together with the inflammatory process, neuropeptides and degenerative changes affecting the nervous fibers are also crucial peripheral mechanisms [ 95 ].…”

Pathological Mechanisms and Therapeutic Targets for Trigeminal Neuropathic Pain

“…Throughout this ascending pathway, noxious information is modulated by both local and descending pain modulatory pathways that either inhibit or facilitate the transmitted sensory information [9,10]. Descending inputs to the Vc arise from the primary somatosensory cortex (SI), secondary somatosensory cortex (SII), insula and from the Rostral Ventromedial Medulla (RVM) [8,11,12,13]. Eventually, the interpretation of noxious stimuli is influenced by a number of affective and cognitive factors that modulate pain.…”

“…Possible causes include nerve trauma [1], compression of the trigeminal nerve root as in trigeminal neuralgia [2], demyelinating disorders, such as multiple sclerosis [3], neoplastic infiltration [4], and familial disorders, such as Charcot-Marie-Tooth disease [5], and secondary to herpetic infections [6]. In many cases, the cause of the neuropathic changes are not understood, however it has been suggested that dysfunction of both peripheral or central nervous systems may contribute [2,7,8]. Orofacial pain conditions are difficult to treat in clinical practice and are often confused with dental pain.…”

Spatial–temporal signature of resting-state BOLD signals in classic trigeminal neuralgia

“… 3 Previous studies of task fMRI in CTN have examined whether this syndrome stems from the central mechanism of a “pain matrix”. 3 , 4 However, variabilities in the activation results obtained by these task-related fMRI studies are quite large. One important reason may be that patients with CTN continuously process dull pain, therefore trigeminal neuralgia is easily concealed by these background activities, leading to greater variations in the functional activation.…”