Trigeminal nerve and phantosmia in primary headaches

Dear Sir

In an interesting review article recently published by Cephalalgia, Coleman et al. (1) perform a detailed analysis of 39 cases of olfactory hallucinations, or phantosmias, occurring in association with primary headache disorders. The authors describe 14 new cases, through data collected on adult patients seen at their Headache Centre, and review 25 literature case reports. The review gives new insights into the clinical characteristics of phantosmia occurring with primary headaches, suggesting that olfactory hallucinations are probably an uncommon but distinctive form of migraine aura. In a section of the review, the authors address possible mechanisms of phantosmia in primary headache and quote various theories: cortical spreading depression, dopaminergic dysfunction and irritation of olfactory bulb, with their pros and cons (1).

In our opinion, trigeminal activation could – and should – also be mentioned as a possible mechanism. Recent findings on transient receptor potential (TRP) channels, localized on primary sensory neurons, including trigeminal ones, underscore the involvement of the trigeminal system in the pathogenesis of various different headache disorders, including migraine and cluster headache. Recently, we have found that umbellulone, an irritant volatile molecule contained in Umbellularia californica (also known as “headache tree”) as a potent TRPA1 agonist, when applied intranasally causes meningeal vasodilatation via a mechanism dependent on TRPA1 and calcitonin gene related peptide (CGRP) (2). Furthermore, other chemical irritants, including ammonia, cigarette smoke, formaldehyde, chlorine and ammonium chloride, which can trigger migraine attacks when inhaled, have been recently identified as TRPA1 agonists.

Ophthalmic and maxillary branches of the trigeminal nerve participate in the afferent chemosensitive innervation of the nasal respiratory epithelium, from which they convey somatosensory sensations, including burning, stinging and cooling sensations (3). Trigeminal activation may indirectly influence olfactory perception, because of the interaction between the trigeminal and olfactory systems, both at peripheral and central level. In particular, there is evidence that trigeminal activation could induce an increase in olfactory sensitivity (3). Hence, the trigeminal nerve has a prominent role, both direct and indirect, in odour perception, and could also be involved in olfactory hallucinations. Indeed, Coleman et al. reported that 11 patients out of 39 with phantosmia describe the odour perceived as ‘burning’ (1), which is a typical description of trigeminal chemesthesis.³