Trigeminal neuralgia (TN) is an exemplary condition of neuropathic facial pain. The clinical diagnosis is relatively easy in patients with typical paroxysmal attacks. Almost 50% of the patients, however, have an atypical phenotype with both paroxysmal and continuous pain, which is distributed in the same territory of the paroxysmal pain. Whereas patients with typical TN are easily diagnosed, and respond fairly well to medical and surgical treatment, those with this atypical form are more difficult to diagnose and to treat. There were two opposite theories about the pathophysiology of the atypical form: investigators proposed either that the continuity of pain merely resulted from progressive damage to the trigeminal nerve in the course of disease or that a central mechanism was involved.
In the past year we were able to exclude both theories, because in patients with the atypical form we found significant abnormalities of the C-related laser evoked potentials, i.e. damage to the unmyelinated fibres. Hence now we believe there must be a different mechanism, probably entailing a greater mechanical insult to the trigeminal root, from the very beginning.
We plan to verify two aspects: 1) using a skin biopsy punch in patients with the atypical form we will measure the intraepidermal nerve fibre density, which must be reduced if the primary damage also involves the ganglion cell bodies or be normal if the site of damage is, as in the typical form of neuralgia, near the root entry zone, and 2) using dedicated 3T, 3D MRI scans we will measure in both typical and atypical forms the degree of atrophy of the trigeminal root. If skin biopsy is normal, thus excluding a supplementary damage to the ganglion, and the atrophy of the root is more severe in the atypical forms, than we will be able to propose the view that the concomitant continuous pain of atypical trigeminal neuralgia is due to a stronger mechanical compression that entails damage to the unmyelinated fibres.
Novelty: in the current literature no studies assessed the difference between patients with typical and atypical forms of trigeminal neuralgia with quantitative, objective measures.
Importance: evaluation and treatment of TN regularly involve clinicians in diverse fields of medicine, including neurology, neuroradiology, neurosurgery, dentistry, maxillofacial surgery, and specialists in pain medicine. Atypical TN poses more dianostic problems because continuous pain is often the result of all sorts of facial pains including dental pains. It is obviously important that these patients are not referred for the wrong surgical intervention. Furthermore the pathophysiology of atypical TN is not yet understood and has so far been only a matter of speculation. Understanding the pathophysiological mechanisms may yield to more targeted medical and surgical treatments. In particular, in case of a stronger mechanical damage to the trigeminal root, these patients should be soon referred for posterior fossa surgery. If there is loss of small ganglion cells, it is better to add the standard treatment for continuous neuropathic pain to the sodium-channel blockers.