Abstract
The report by Sesso (1) in this issue of Cephalalgia raises an interesting clinical question and fundamentally important physiological issue: the relationship between SUNCT (Short-lasting Unilateral Neuralgiform pain with Conjunctival Injection and Tearing) and trigeminal neuralgia. SUNCT is a relatively newly described syndrome (2), and its major differential diagnosis in typical cases is trigeminal neuralgia. Are these two pathogenically distinct conditions or ends of a spectrum?
Based on evolution of the clinical phenotype from trigeminal neuralgia to SUNCT, it has been argued that these conditions can transform one to another, trigeminal neuralgia to SUNCT. Benoliel and Sharav (3) reported six cases of what was classified as trigeminal neuralgia with lacrimation together with 16 without lacrimation. Descriptions of trigeminal neuralgia with lacrimation can be found in the writings of Gowers (4), Collier (5) and Kinnier Wilson (6). Bouhassira and colleagues (7) have argued that SUNCT may be a form of transformed trigeminal neuralgia based on the shared phenomenology. The carbamazepine response in trigeminal neuralgia is generally very rewarding, and SUNCT patients comment that carbamazepine is helpful, as did case 6 of Benoliel and colleagues (3), although usually with less enthusiasm.
Sjaastad (8) has made comments on the distinction between SUNCT and trigeminal neuralgia by reporting the characteristics of first division trigeminal neuralgia accepting some degree of autonomic activation. Both conditions are relatively short-lasting, having attacks in seconds, and may have few or many attacks a day. However, SUNCT typically has prominent cranial autonomic symptoms (9), such as tearing and conjunctival injection, which has been proposed to be activation of the trigeminal-autonomic reflex (10). It has been suggested that SUNCT be classified with other syndromes with prominent cranial autonomic symptoms, such as cluster headache and paroxysmal hemicrania, as trigeminal autonomic cephalalgias (TACs) (11).
We have seen lacrimation with experimental head pain from capsacin injection (12), and it is recognized with other forms of secondary trigeminal neuropathic pain (13). There is considerable experimental animal literature to document that stimulation of trigeminal afferents can result in cranial autonomic outflow, the trigeminal autonomic reflex (10). We conclude that some degree of cranial parasympathetic activation is a normal physiological response to nociceptive input in the first division of the trigeminal nerve.
On this background how can we reconcile the question of the relationship between SUNCT and trigeminal neuralgia? If we accept that first division nociceptive input results in cranial parasympathetic activation of some degree, perhaps often subclinical, then it would be expected to see such symptoms in trigeminal neuralgia, or indeed experimental pain, as we do. Indeed, these symptoms are sometimes seen in migraine, and can result in appropriate release of neuropeptide marker (14). It could be suggested that the key feature of trigeminal autonomic syndromes, such as SUNCT, is the degree not presence of cranial autonomic activation. This may relate to central disinhibition of this reflex. Certainly, there are direct hypothalamic–trigeminal connections (15), and the unifying finding for SUNCT (16) and cluster headache (17) seems to be hypothalamic activation. Operationally, this leads to the clinical markers of the degree of cranial parasympathetic activation in SUNCT, and the response to classical treatment with carbamazepine, and the finding of an aberrant vascular loop in trigeminal neuralgia, as pointers to classification. This is not ideal and more data are required to better differentiate these conditions.
As with many primary headache syndromes, phenotype characterization is only the first step in unravelling the pathogenesis of the condition. For the moment we would argue that trigeminal neuralgia and SUNCT should be classified separately. Since lacrimation can occur in virtually any situation in which ophthalmic division activation is seen, it cannot be given as a reason to lump the two conditions. Operationally, short-lasting pains in the distribution of the ophthalmic division of the trigeminal nerve with prominent cranial autonomic (parasympathetic) activation is SUNCT. As is often the case, the rarities illustrate some interesting physiological principles: here the trigeminal-autonomic reflex. It is clinically useful to remember that modest cranial parasympathetic activation can occur in any form of first division nociceptive activation, whether primary, such as in migraine, or secondary, such as experimental head pain or trigeminal neuralgia.