Understanding Cluster Headache Using Magnetic Resonance Imaging (from) Frontiers in Science

[Juss]

I am hoping to conjure a conversation. 

Hypothalamic activity is integral in Cluster Headache, as is the activation of the Anterior Cingulate Cortex. The journal presented some interesting current insights using DTI, fMRI, and MRI.

As far as it appears, great, the hypothalamus is hijacked, what medications can regulate activity? Calcium, Magnesium, Vitamin D, Prednisone, other antihistaminics, all help, but seem to miss the mark.

I can think of two approaches but both are unfounded. Intranasal oxytocin, and possibly a Dual Orexin Receptor Agonist, suvorexant comes to mind. 

Any thoughts?

Here is the journal about Understanding CH by MRI 

https://www.frontiersin.org/articles/10.3389/fneur.2020.00535/full

 

[Juss]

Orexins, also known as hypocretins, have been widely implicated in homeostatic regulation; and dysfunction of the orexinergic system in migraine has recently been explored^91–93. The orexin family is comprised of two neuropeptides, orexin A (OXA) and orexin B (OXB), which are derived from the precursor peptide, prepro-orexin⁹⁴. Orexin A is 33 amino acids in length, while orexin B is 28 residues, and mature versions of these peptides are entirely (OXA) or highly (OXB) conserved in mammals⁹⁵. Although these peptides are synthesized exclusively in the dorsolateral hypothalamus, orexinergic neurons project throughout the CNS, including to other hypothalamic nuclei, thalamus, cortex, trigeminal nucleus caudalis, and spinal cord⁹¹. Both orexin peptides bind to orexin receptor 1 (ORX1) and orexin receptor 2 (ORX2), both of which are Gq GPCRs, and as such activation results in increased intracellular Ca²⁺⁹⁴. OXA has equal affinity for both orexin receptors, while OXB has a ten-fold increased affinity for OXR2⁹⁴. The orexin receptors are broadly expressed in the brain, and usually correspond with orexin peptide expression^91, 93.

The orexinergic system is involved in the dynamic regulation of a number of physiological processes; including feeding, sleep/wake cycle, stress, and motivation⁹⁶. Many of these processes are disrupted during migraine, particularly in the premonitory phase. For example, changes in appetite are often observed during headache, and disruption to normal feeding patterns are considered a potential migraine trigger. Orexins may regulate this aspect of headache disorders, as they play an important role in appetite and food consumption⁹⁶. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986366/