Authors' reply to the comment by Fusconi etal.

Abstract

We appreciate Drs Fusconi et al.'s (2016) interest in our original research ‘Nigrostriatal dopaminergic depletion produces orofacial static mechanical allodynia’ (Dieb et al., 2015) describing orofacial static mechanical allodynia developed following mesencephalic dopamine lesions, implicating PKCγ-pERK1/2neuronal networks. The intent of our study was neither to define a differential diagnosis between idiopathic and neuropathic orofacial pain nor to explore precisely the implications of the dopaminergic system in Eagle's syndrome. Instead, we tried to answer, using an animal model, an important clinical question, namely whether a central dopaminergic system dysfunction in some patients (depression, Parkinson's disease… etc.) could be implicated ‘per se’ in the development of trigeminal neuropathic pain. Our proposed experimental model could be also relevant to study idiopathic painful conditions, such as persistent idiopathic facial pain (PIFP) or atypical facial algia (AFA), atypical odontalgia (AO) and burning mouth syndrome (BMS). These chronic (orofacial) pain conditions are usually grouped together under the concept of idiopathic orofacial pain and remain a diagnostic and therapeutic challenge for both clinicians and patients (for review, see Forssell et al., 2015). Moreover, central dopamine depletion may reveal some systemic painful disease such as fibromyalgia and restless legs syndrome (Wood, 2008). Some cases of Parkinsonism (nigrostriatal dopaminergic depletion) and some facial hemispasms associated with intractable trigeminal neuralgia were reported to be associated with arterial compression of the cerebral peduncle by the posterior cerebral artery. This compression may frequently be observed on magnetic resonance imaging (MRI) studies. These cases improved with nerve decompression (Jannetta et al., 2011; Hitchon et al., 2015). These reports could reflect a common mechanism between Parkinson's disease and trigeminal neuralgia, both cases clearly involving the arterial compression of the central neuronal peduncle (Jannetta et al., 2011). Furthermore, a similar scenario could be suspected after peripheral compression of carotid, autonomic nervous system and/or the other regional cranial nerves (e.g. nerve IX) by the elongated styloid process in Eagle's syndrome (ES). In agreement with Fusconi et al., we strongly believe that ES must be considered as an orofacial pain and should not be confused with other neurological or idiopathic pain syndromes. Eagle's syndrome has also been called: stylohyoid complex syndrome (SHCS), stylohyoid syndrome, styloid syndrome, elongated process syndrome, stylalgia, styloid–stylohyoid syndrome, styloid dysphagia, chronic styloid angina, temporal rheumatic styloiditis, stylocarotid syndrome and the Garel-Bernfeld syndrome (for review, see Montalbetti et al., 1995). ES is a rarely identified clinical entity involving the oro-maxillo-facial region, described as early as 1652 by the Italian surgeon Marchetti, But in 1937, Eagle, an American otolaryngologist, characterized in great detail this syndrome which would later bear his name (Montalbetti et al., 1995). By definition, Eagle considered any styloid process longer than 25 mm in an adult patient to be abnormal. He found that 4% of the population had elongated styloid processes, but approximately only 4% of these individuals actually suffered from orofacial pain. Eagle also subdivided this syndrome into two categories: classic type and carotid artery type. The classic type of Eagle's syndrome, almost constantly occurs after tonsillectomy, the most common presentation being a sensation of a foreign body in the oropharyngeal region, dull and nagging pain without a lancinating neuralgic quality; during swallowing, this painful sensation could sometimes refer to the ear region. The carotid artery type occurs by compressing the internal or the external carotid artery by an elongated styloid process, but may also present with other dysfunctional symptomatic symptoms caused by irritation of the sympathetic nerve plexus. By compressing the internal carotid artery, the pain is generally felt within the lateral region of the head or around the eye. In the case of external carotid artery compression, pain is referred to the infraorbital region and increases with the rotation of the head. In addition, transient visual loss, dizziness and syncope may also occur. It should be noted that despite their differences, both types of ES share a common etiopathogenic mechanism, namely local trauma resulting from excessive mechanical stimulation of an elongated styloid process. Nevertheless, it is not quite clear whether the resulting pain can be considered of inflammatory or neuropathic origin (the latter potentially resulting from chronic compression of autonomic nerve branches surrounding the carotid artery in carotid artery type ES). Therefore, we suggest a revision of the definition of Eagle's syndrome, as proposed by the International Classification of Headache Disorders 3rd edition (ICHD-3 beta version) to take into account the questions surrounding the exact nature (inflammatory vs. neuropathic) of this rare painful condition. Diagnosis of Eagle's syndrome relies on both clinical and radiological examinations. As such, pharyngeal palpation is of great importance during clinical examination, because although normal length styloid processes are not palpable, palpation of an elongated styloid process can elicit a pain sensation. For routine radiological assessment, orthopantomography has a high sensitivity to detect elongated styloid processes. However, cone-beam computed tomography (CBCT) offers the best precision regarding the anatomical position of the styloid process. Differentiating ES from BMS is relatively easy, as pain in ES is of a dull and nagging nature without a lancinating neuralgic quality or burning sensation as compared with BMS. Other facial pain syndromes such as PIFP or AO should be considered in the differential. PIFP (or AFA) describes chronic pain within the orofacial region innervated by the trigeminal nerve that does not fit in any other orofacial pain diagnostic category. It is described as a severe ache, crushing or burning sensation of long duration, continuous throughout the day, unilateral and without any autonomic signs or symptoms. Moreover, no abnormalities or pathologies can be detected during clinical or radiological examination (Zakrzewska, 2013). Atypical odontalgia, also termed psychogenic toothache, phantom tooth pain or persistent dentoalveolar pain disorder is very similar in many respects to AFA, without any identifiable cause, but perceived to be in relation with one or multiple teeth (Forssell et al., 2015). In Woda et al., the two entities AFA and AO were considered as atypical facial pains (Woda et al., 2005). Taking into account the specific clinical and radiological characteristics of ES as compared with other facial pain syndromes, it seems that Eagle's syndrome can easily be differentiated from idiopathic orofacial pain. However, we do agree with Fusconi et al. (2016) that ES must be excluded before suggesting any type of idiopathic orofacial pain (Fusconi et al., 2016). Furthermore, as Fusconi et al. reported earlier (Fusconi et al., 2014), we also suggest a re-evaluation of the definition of ES proposed by the International Classification of Headache Disorders 3rd edition (ICHD-3 beta version) (Headache Classification Committee of the International Headache Society (IHS), 2013), as all relevant subtypes of this syndrome have not been adequately described in this classification. In conclusion, the relationship between dopamine depletion and ES has never been reported so far. ES must be excluded before considering any idiopathic pain diagnosis, and central dopaminergic dysfunction might be taken into consideration in both diagnosis and treatment of idiopathic orofacial pain such as AFA or BMS.