Pathophysiological mechanisms in trigeminal neuralgia. The Impact of sex, neurovascular compression, and nerve fibre function

This PhD thesis investigates the pathophysiological mechanisms underlying trigeminal neuralgia (TN), with a focus on how sex, neurovascular compression, and nerve fibre function influence the clinical presentation and neurophysiological characteristics of this unique chronic neuropathic pain disorder. Key findings reveal an association between female sex and idiopathic TN, suggesting the involvement of additional etiological factors beyond neurovascular compression in women, supporting a multi-hit model of disease. This association, along with the poorer tolerability of first-line drugs (carbamazepine and oxcarbazepine) in women, underscores the significant burden TN places on female patients and highlights the need for sex-specific therapeutic approaches. A latency asymmetry exceeding 0.5 ms between the affected and unaffected sides in trigeminal reflexes is predictive of classical TN, likely reflecting the impact of neurovascular compression on large-myelinated nerve fibres. In patients with concomitant continuous pain, reduced C fibre-related laser- evoked potential (LEP) amplitude on the affected side suggests that selective damage to unmyelinated C fibers, potentially reflecting axonal loss, may be the primary mechanism behind this kind of pain. Such axonal loss may result in abnormal activity in anatomically denervated trigeminal nociceptive second- order neurons, a mechanism known as “denervation supersensitivity”. Overall, these findings enhance our understanding of TN pathophysiology and lay the groundwork for more patient-tailored treatment approaches.