Migraine headache attacks can be triggered by many factors through trigeminal nerve (TN) or non-TN pathways. Many factors including odor stimulation, stress, menstruation, weather change and sunlight have been identified as trigger factors for migraine attacks through non-TN pathway [7–9]. On the other hand, clinical observational studies have shown that some pericranial tenderness areas existing in migraine patients are trigger points for migraine attack through TN or spinal nerve pathways [1]. Case studies have shown that petrous apicitis can initiate and sustain the recurrence of migraine headaches through TN pathway [5]. Here, we report, for the first time, that migraine headaches were triggered exclusively by palpation of a purulent infection on a regional skin innervated by the second branch (V2) of TN. This case indicates that TN terminal stimulation provoked a migraine headache attacking under the condition of skin infection in the area innervated by TN terminals, while a TN terminal stimulation by palpating or pressing the symmetrical area without skin infection on the other side of the face did not evoke headache attacking. This is consistent with the report that noxious craniofacial stimulation to TN terminals has an amplifying effect on migraine headache induced by glyceryl trinitrate [10]. Currently, there is no literature report showing that TN stimulation can directly evoke migraine headache attacking though TN block is effective in the treatment of episodic and chronic migraine [11]. Thus, it might be proposed that TN stimulation itself is not enough to initiate a migraine or trigger a migraine headache attack, but, under certain condition causing increased sensitivity of TN or central system, TN stimulation can initiate a migraine or trigger a migraine headache attack.
On the other hand, migraine patients are found to be infrequently but not uncommonly accompanied with facial symptoms including facial pain associated with TN [12]. And trigeminal neuralgia development is at high risk in patients with migraine [13]. Recently, episodic migraine patients were detected with TN microstructural changes under magnetic resonance imaging study [14], and this microstructural changes were presented with disrupted myelin sheaths under electron microscopic study [15]. These literature reports indicate that migraine attacking may affect the TN with presentations on face, especially on the area innervated by the V2 of TN [12]. All these previous reports show migraine patients may have peripheral sensory presentations associated with TN or involvement of TN itself, a peripheral presentation of medication-resistant skin infection associated with migraine has never been reported. Here, we report, for the first time, that antibiotic medication-resistant chronic facial infection on the regional skin innervated by V2 of TN was ceased by an effective treatment of migraine, indicating that migraine processing in the central nervous system can influence skin immunomodulation through TN.
Folliculitis is a type of uncomplicated skin and skin structure infection (uSSSI) which includes cellulitis, simple abscesses, impetigo, erysipelas and folliculitis. The common pathogenic bacteria of uSSSI are staphylococcus aureus and streptococcus pyogenes [16]. Recently, a study of necrotizing fasciitis demonstrated that streptococcus pyogenes secretes streptolysin to directly activate nociceptor neurons inducing pain during infection. The activated neurons in spinal ganglion, in turn, release the calcitonin gene-related peptide (CGRP) from the neuronal fiber terminals into the infected tissues, which inhibits the neutrophil recruiting and phagocytic killing of streptococcus pyogenes [17]. On the other hand, multiple studies have indicated that abundant CGRP secreted by trigeminal ganglion (TG) neurons interacts with adjacent neurons and satellite glial cells within TG to perpetuate both peripheral and central sensitization [18], and it is supposed with multiple evidences that central sensitization increase the propensity of either an external or an internal stimulus to trigger a migraine headache attack [18]. Thus, in our patient, it might be proposed that purulent infection around the nosewing may cause an activation of TG nociceptor neurons, the activated TG neurons secretes CGRP to sensitize the TN and brain and a migraine headache attack can be triggered by an external stimulus, a palpation of the skin, which may not be enough to generate a migraine attack in normal condition. Meanwhile, the activated TG neurons release CGRP from the TN terminals into the infected facial skin tissues causing a chronic infection as CGRP inhibits the phagocytic killing of pathogenic bacteria.
In conclusion, a bidirectional relationship between migraine headaches and chronic infection of regional skin innervated by TN terminals can be determined by the triggering role of TN stimulation under a condition of chronic regional skin infection, and by the maintaining role of migraine headaches in the chronic regional skin infection. This peripheral and central interaction in migraine might be associated with neuropeptide CGRP released from TG neurons.