Trigeminal neuralgia (TN) primarily results from irritation or compression of the trigeminal nerve, a major cranial nerve responsible for facial sensation. The most common cause is a blood vessel pressing on the nerve, a condition referred to as vascular compression. Other potential causes involve conditions that damage the myelin sheath, the protective covering of the nerve, such as Multiple Sclerosis (MS), or the presence of a tumor exerting pressure on the trigeminal nerve.

Contributing factors and less common causes of trigeminal neuralgia include:
* Multiple Sclerosis (MS)
* Damage to the myelin sheath
* Tumors compressing the trigeminal nerve
* Stroke or facial trauma
* Genetic predisposition
* Advanced age
* High blood pressure
* Smoking