The Molecular Basis and Pathophysiology of Trigeminal Neuralgia

Abstract

Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.

Radiomics nomogram based on MRI water imaging identifying symptomatic nerves of patients with primary trigeminal neuralgia: A preliminary study

“…[9] Demyelination can lead to dysregulation of voltagegated sodium channels (Nav), contributing to pain. [9,10] Additionally, clinical features such as morphological changes in the Merkel cavity (MC), reduced trigeminal pons angle (TPA) and atrophic thinning of affected nerves may play roles in PTN etiology. [11][12][13] Microscopic factors, such as dysregulated expression of long-stranded noncoding RNA, micro-demyelination due to arachnoid adhesions, microcholesteatoma, and narrowing of the foramen ovale are also implicated.…”

Association between trigeminal neuralgia and degenerative cervical myelopathy: A cross‐sectional study using US data

“…TN typically occurs in middle to older aged adults and may be exacerbated when stimuli are applied to regions innervated by the trigeminal pathway 2 . This condition has a lifetime prevalence of 0.03% to 0.3% 3 . The prevailing hypothesis regarding the etiology of TN is a neurovascular compression of the intracranial portion of the trigeminal nerve 4 .…”

“…2 This condition has a lifetime prevalence of 0.03% to 0.3%. 3 The prevailing hypothesis regarding the etiology of TN is a…”

Evaluation of Endoscopic Microvascular Decompression for Trigeminal Neuralgia

“…It is extremely uncommon to only involve V1. There are two categories of TGN: [1] classical or primary TGN, and [2] secondary TGN. Vascular loop is responsible for "classical TGN".…”

“…Vascular loop is responsible for "classical TGN". Secondary TGN results from multiple sclerosis, postherpetic neuralgia, post-traumatic neuralgia, and space-occupying lesions like meningioma, arterio-venous malformation, and CPA tumor [1,2] . Due to its successful surgical outcomes and ability to avoid long-term recurrence, microvascular decompression [MVD] has come to be recognized as the preferred surgical method for the treatment of trigeminal neuralgia [TN].…”