The afferent arm of the hiccup reflex consists of the phrenic and vagus nerves as well as the thoracic sympathetic chain. There is no well-defined central hiccup center; instead, there is an intensive interconnection among the hypothalamus, medullary reticular formation, respiratory center, and cranial nerve nuclei. The efferent limb of the reflux uses the phrenic nerve, the recurrent laryngeal branch of the vagus nerve, and the motor nerves to the anterior scalene and intercostal muscles.

As noted above, hiccups are produced by spasmodic contraction of the inspiratory muscles (diaphragm and intercostals) against a closed glottis, a breakdown in the normal relationship between inspiration and glottic closure. Inspiration normally inhibits glottic closure and maintains an open airway. During swallowing, the stimulation of glottic closure inhibits inspiration, preventing aspiration. In some manner, the hiccup reflex disrupts the connection between these two processes so that 30 to 40 ms after the onset of inspiration, glottic closure is stimulated. 23 In most cases where a specific cause can be assigned, hiccups appear to result from stimulation, inflammation, or injury to one of the nerves of the reflex arc.

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