Abstract In response to “ Trigeminal neuralgia: drug therapy: The new German guideline”, a 17-year single center experience (Duke University Medical Center) with over 5000 treated patients is shared. Recommendations as in the updated German guidelines are endorsed, however extended by pointing out the critical relevance of very early intervention with as-needed medications that are rapidly absorbed and self-applied by patients in case of impending attack, which in most cases is reliably anticipated by patients thus opening up a time-window to implement such treatments. These treatments are rapid-acting carbazines, clonazepam and other off-label medications, formulated either as liquid, orally-dissolving tablet or nasal spray. In addition, pain-evoked blood pressure peaks deserve attention and possible early intervention using as-needed treatments to prevent a vicious pain-hypertension feedforward. In terms of antineuralgic medical maintenance treatment, the robustly beneficial experience with lacosamide is shared, in particular the combination of lacosamide or other anti-neuralgic medical regimens with low-dose naltrexone. Recent German guidelines on medical therapy of trigeminal neuralgia are relevant and timely because trigeminal nerve pain sufferers endure one of the worst forms of pain humans can suffer. Bad pain readily becomes worse once patients seek urgent medical attention which dials up their stress levels and faciliates a detrimental feed-forward. At one point, patients lose the ability to speak and to communicate rationally because of the impact of their trigeminal pain. In such a situation of acute pain distress, and also in follow-up, patients suffering from trigeminal pain are often times mistreated, means too late, too low of a dose, or not at all. This is so in the US, in Germany and in many other parts of the world, thus spread of well-informed information on trigeminal pain disorders and how to treat them safely and effectively can help address the severe unmet medical need of trigeminal pain. Importantly, episodic trigeminal nerve pain also shares an element of post-traumatic stress disorder – the next devastating, supra-maximal and destructive pain attack can hit the patient any time, she/he feels absolutely helplessly exposed, a no-option victim at the receiving end of viciou pain to their head and face, and threatened in their existence. “Off-label” medical therapy in real-world clinical practice is essentially relevant to enhance management of trigeminal nerve pain. This can be in the context of combination therapy where components complement each other, and in the context of personalized medicine approaches. The translational-medical mandate of trigeminal nerve pain disorders is as compelling as it is timely. A decisive factor for all stakeholders to score a win against this formidable foe is closely coordinated collaboration and alignment between clinical research and development, and basic science. Here I will share my experience with >5000 patients seen over 17 years (2004-2021) whom I had the privilege to serve in the two pain-focused clinics at Duke University Medical Center (Durham […]