Abstract
The aim of this study was to report on two patients with recurrent, paroxysmal, extracephalic pain triggered by yawning. Pain with yawning may occur in several conditions (secondary yawning pain) or develop in the absence of precipitating lesions (primary yawning pain). Primary yawning pain is normally of cephalic location. Methods used were clinical neurological examinations, magnetic resonance imaging of the brain, computerized head tomography, electroencephalogram, blink reflex studies and Panorex X-ray views of the skull. The first patient had intense right shoulder pain and brief apnea for 2 years triggered by yawning. The second patient had yawning pain referred to an area of the neck where a thyroid tumour (Hürthle cell carcinoma) was later found. Neither of the two patients could precipitate their pain with imitation of yawning and neither had evidence of Eagle syndrome. Only the second patient had a history of migraine. Yawning pain may have an extratrigeminal and extracephalic distribution. It rarely serves to identify a lesion underlying the area where the pain is perceived.
Introduction
Yawning may trigger cephalic, pharyngeal or upper cervical pain in trigeminal, geniculate and glossopharyngeal neuralgias, temporomandibular joint dysfunction (TMJ) and Eagle syndrome (ES) (secondary yawning pain) (1, 2). In primary yawning headache (PYH), no underlying lesion or disorders are present, therefore it represents an isolated, benign condition of minor clinical significance (2). In PYH the pain is cephalic in distribution.
ES is probably the form of secondary yawning pain less recognized by neurologists. It is characterized by neuralgic or steady pharyngeal pain radiating to the ear, mimicking carotidynia and glossopharyngeal neuralgia. Calcification or elongation of the stylohyoid ligament causes ES. Surgical resection of the elongated styloid process is curative (3). Two patients are described with yawning pain of extracephalic location. One had an underlying lesion in the area where the pain was perceived. Neither of the two had evidence of ES.
Case reports
Case 1
A 45-year-old male reported episodes characterized by recurrent, intense, steady right shoulder and arm pain triggered by yawning and associated with inability to breathe spontaneously of abrupt onset. Symptoms developed 2 years earlier. He had to take voluntary control of his breathing during these episodes. He had no numbness of the arms, chest pain or palpitations during these episodes that lasted a maximum of 2 min. He had no other precipitants of the pain. Witnesses never saw him change colours or act inappropriately. He had history of gout and of an old sacral radiculopathy. One uncle had Parkinson's disease. He took allopurinol for his gout. His general physical examination was normal. On neurological examination he deviated simultaneously his jaw to the same side of his tongue when asked to wiggle his tongue side-to-side (linguo-pterygoid synkinesis). Facial gestures or wide opening of the mouth did not reproduce the pain. Brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were normal. His cervical MRI showed mild central disc bulging at C5 and C6 levels, causing no root encroachments or spinal cord impingement. Cranial nerve testing including blink reflexes, mental and facial nerve responses and electromyography (EMG) of the facial muscles were normal. Palpation of the tonsillar fossa and Panorex X-rays of the skull were normal. He was reassured about the benign nature of his condition and medication was not prescribed.
Case 2
A 84-year-old retired female nurse was referred for neurological evaluation because of anterior cervical piercing pain, precipitated by yawning, for the last 9 months. She had history of migraine with visual aura, right eye blindness, anti-phospholipid antibody syndrome, hypothyroidism, arteriosclerotic heart disease, deep venous thrombosis, ventricular fibrillation, aortocoronary bypass, aortic valve replacement and pacemaker insertion. Palpation of the thyroid gland revealed a mobile painless mass over the right upper pole of the thyroid. She was totally blind on her right eye. Her vital signs and neurological examination were normal otherwise. Imitation of yawning or forceful opening of the mouth did not cause any neck pain. CT of the head showed silent lacunar strokes and leukoaraiosis. Carotid Doppler ultrasound of the neck revealed no stenotic lesions. Panorex views of the skull showed no elongation of the styloid. A thyroid ultrasound demonstrated a 1.9 × 2.6 × 1.7 cm solid nodule over the right upper pole. Aspiration of the nodule was diagnostic of Hürthle cell carcinoma. Conservative management was advised given her age and lack of symptoms, other than yawning pain.
Discussion
Yawning is a normal phenomenon in mammals signifying drowsiness, fatigue, hunger or boredom (1). In male rodents, it represents pre-coital behaviour that can be precipitated by cortical spreading depression (4). Yawning is under the complex control of several neurotransmitters including dopamine, nitric oxide, glutamate, GABA, serotonin, ACTH, MSH, sexual hormones and opioid peptides (5). Dopamine in particular, is of greater importance. Dopamine increases oxytocin synthesis in the paraventricular nucleus of the hypothalamus, subsequently inducing yawning, by activating cholinergic transmission in the hippocampus. Ultimately, acetylcholine acts upon the muscarinic receptors of the effectors (5). Of clinical relevance is that compulsive yawning may constitute a migraine prodrome and yawning is readily induced in migraineurs after the administration of sublingual apomorphine, a dopamine agonist drug (6, 7). This susceptibility to dopamine seems to arise from the expression of D2 receptor genes in those patients exhibiting pre-cephalgic yawning that results in central and peripheral (lymphocyte) dopamine receptor up-regulation and hypersensitivity (8–10). Also of interest, is the association of migraine and restless legs, as the latter is a condition based on central dopaminergic dysfunction (11, 12). Conversely, levodopa alleviates pathological yawning associated with periodic leg movements of sleep (13).
The pathogenesis of yawning pain is unclear. The first patient herein described had no history of migraine to suggest underlying dopaminergic dysfunction and, although the second patient had history of migraine, her pain localized to the area occupied by the thyroid tumour only, and was not pre- or peri-cephalgic in nature. Unfortunately, 18 F-dopa PET scan could not be performed on these patients, in order to assess the potential role of central dopaminergic dysfunction on their symptoms, nor were they tested for apomorphine hypersensitivity. It can be speculated that a reflex arch is formed between cranial and capsular temporomandibular stretch receptors and trigeminal nerve fibres, including those travelling through the upper cervical nerves. The pain experienced by these two patients, however, included lower cervical dermatomes outside the expected trigeminal zone of innervation. In any event, a facilitatory mediation by the cerebral hemispheres needs to be postulated as the simple imitation of yawning, normally activating stretch receptors, did not reproduce their pain. Participation of the medullary centres in the first patient is suggested by his loss of spontaneous breathing, immediately following yawning-induced pain.
The cause of the yawning-respiratory synkineses experienced by the first patient is also unknown. His pain was not reproduced by eructation, as experienced by a previously reported patient with primary yawning headache (2). Its occurrence could have indicated the involvement of C3, C4 and C5 spinal cord segments innervating the diaphragm. Brainstem lesion, demyelination and aberrant innervation were ruled out by a normal brain MRI and cranial nerve electrophysiological testing. Although yawning may be an exceptional epileptic manifestation, there is no justification to support the diagnosis of partial reflex epilepsy on this patient either, in the absence of additional ictal symptoms and EEG abnormalities. Cervical myelopathy or radiculopathy could not be adduced as a mechanism for his right shoulder pain. His cervical MRI showed only mild central disc bulging without root encroachment and there were no other clinical signs of radiculopathy.
Of additional interest is that the cervical pain reported by the second patient was localized precisely to the area of the thyroid tumour, even when the palpation of the tumour did not elicit pain. She had no clinical evidence of paraneoplastic peripheral neuropathy or central nervous system metastatic lesions, in order to postulate an explanatory mechanism on those bases. Motor activity may result in paroxysmal referred pain, experienced away from the anatomic area engaged in the movements. Rarely, this referred pain may serve to diagnose an underlying lesion. I reported earlier, two patients with pain during the act of masturbation (14). When achieving orgasm, the first patient had piercing (ice pick-like) pain in the neck. His imaging studies revealed advanced cervical spondylosis and spinal cord compression. This second patient suffered pain in the groin, testicle and rectal area. He had an intraspinal lipoma and tethered cord. Although probable stretching of the tumour tissue occurred during yawning in the second patient, it is unexplained why stretching of the same tissular area with the imitation of yawning or with palpation did not reproduce the pain.
In conclusion, yawning pain may have an extracephalic localization and similar to its cephalic counterpart, it may have an underlying cause (secondary yawning pain) or, as exemplified by the first patient, have no apparent cause (primary yawning pain). Following the IHS classification, primary yawning pain (or PYH) with and without extracephalic manifestation, may be classified under ‘miscellaneous headaches not associated with a structural lesion’, while secondary yawning pain (i.e. ES) may be classified under ‘headache or facial pain associated with disorder of cranium, neck, eyes, nose, sinuses, teeth, mouths or other facial or cranial structures’. Alternatively, both conditions could be listed as ‘headache not classifiable’.