The Impact of Intravenous Administration of ACMP (Eptinezumab) on the Treatment of Atypical Resistant Facial Pain

Facial pain in the trigeminal nerve region, which is not a migraine headache (e.g., cluster headaches, trigeminal neuralgia, burning mouth syndrome), is often very persistent and difficult to treat. Despite the use of all available treatment methods is often unsuccessful. Research findings suggest that, similar to the mechanisms of migraine headache, the increased concentration of calcitonin gene-related peptide (CGRP) plays an important role in the mechanisms of facial pain. Trigeminal neuralgia has already been treated with intravenous administration of anti-CGRP monoclonal antibodies (ACMP), such as eptinezumab.

In facial pain, as in chronic migraine, both peripheral and central nervous system sensitization can occur. Central sensitization is a poorly understood biological phenomenon, although some mechanisms are known. According to current knowledge and clinical experience, CGRP likely plays a central role in central sensitization that occurs in facial pain. It is known that in chronic migraine, the concentration of CGRP in the blood is elevated.

The peripheral mechanism of sensitization is not entirely clear, but it is likely that the peripheral part of the autonomic nervous system, specifically the parasympathetic system, plays an important role. The trigeminovascular reflex, a consequence of the autonomic segmental reflex, causes peripheral sensitization. Neurogenic inflammation also occurs. Neurogenic inflammation in the meninges further sensitizes the trigeminal nerve fibers.

CGRP is important for regulating physiological processes in the human body. It is also important for the sensitization of the peripheral nervous system, which can lead to central sensitization and create a vicious cycle. Central sensitization is a source of pro-inflammatory factors that promote neurogenic inflammation.

The level of CGRP in the body depends on its production and removal from the blood. ACMP effectively inactivate CGRP, thus reducing the number of migraine episodes and their intensity. Therefore, we hypothesize that intravenous administration of ACMP will similarly disrupt central sensitization in facial pain as it does in migraine headaches. Pharmacokinetic studies with eptinezumab have shown that intravenous administration of eptinezumab leads to an immediate peak concentration of ACMP, while subcutaneous administration reaches this effect only after several days. Since the biological availability of ACMP is significantly higher in the first few days, this may lead to the most effective reduction in CGRP influx and a probable clinical reduction in facial pain.