Abstract
Trigeminal autonomic cephalalgia (TAC) encompasses 4 unique primary headache types: cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms. They are grouped on the basis of their shared clinical features of unilateral headache of varying durations and ipsilateral cranial autonomic symptoms. The shared clinical features reflect the underlying activation of the trigeminal–autonomic reflex. The treatment for TACs has been limited and not specific to the underlying pathogenesis. There is a proportion of patients who are refractory or intolerant to the current standard medical treatment. From instrumental bench work research and neuroimaging studies, there are new therapeutic targets identified in TACs. Treatment has become more targeted and aimed towards the pathogenesis of the conditions. The therapeutic targets range from the macroscopic and structural level down to the molecular and receptor level. The structural targets for surgical and noninvasive neuromodulation include central neuromodulation targets: posterior hypothalamus and, high cervical nerves, and peripheral neuromodulation targets: occipital nerves, sphenopalatine ganglion, and vagus nerve. In this review, we will also discuss the neuropeptide and molecular targets, in particular, calcitonin gene-related peptide, somatostatin, transient receptor potential vanilloid-1 receptor, nitric oxide, melatonin, orexin, pituitary adenylate cyclase-activating polypeptide, and glutamate.
Highlights
Trigeminal autonomic cephalalgia (TAC) encompasses 4 primary headache disorders that are characterized by their shared unique features
The results showed that there was an immediate improvement in pain as well as a neuromodulation effect with reduced attack frequency, duration, and intensity
The study found that cluster headache patients have altered kynurenine metabolites when compared with healthy controls and, in particular, reduced levels of kynurenic acid support the hypothesis that NMDA receptors are overactive in CH and a potential therapeutic target
Summary
Trigeminal autonomic cephalalgia (TAC) encompasses 4 primary headache disorders that are characterized by their shared unique features. In one study with 83 chronic cluster headache patients, they showed for a single injection to the greater occipital nerve using 80 mg methylprednisolone and 2 mL of 2% lidocaine, the median duration of benefit was 21 days, with the main side effects of lightheadedness, neck stiffness, and continuous pain at the site of injection [67].
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