William A. Whitelaw, a professor in the department of medicine at the University of Calgary, explains.
If a person gets hiccups and wants to know what has set them off, there is a long list of medical or physiological disorders that are associated with hiccups and seem to cause them. The most common by far is distension or expansion of the stomach and movement of stomach acid into the esophagus. After that, a disease or irritation in the thorax could be to blame. Irritation of the phrenic nerve (the nerve to the diaphragm) or the diaphragm is often cited as a cause of hiccups, but this is only speculation about the exact mechanism. Hiccups can also arise from a variety of neurological lesions, many of them involving the brain stem, or some metabolic disorders (particularly renal failure). Medications, often ones that promote acid reflux into the esophagus, and a variety of other disorders have also been linked to hiccups.
In medical practice, however, we do not start looking for any of these causes unless the hiccups are very persistent or if they came on very dramatically for no obvious reason. For ordinary bothersome hiccups that come back or stay longer than usual, treatment for stomach acid reflux is usually offered before other investigations are done.
In regards to the physiological process behind hiccuping, some information and speculations exist, but a complete answer has not yet been determined. A hiccup is not simply a twitch of the diaphragm but a complex motor act. During one, the diaphragm and the complete set of inspiratory muscles (intercostal muscles, neck muscles and others) make a sudden, very strong, contraction. The expiratory muscles are also strongly inhibited. Just after the contraction begins, the glottis (commonly called the vocal cords) clamp shut, making the "hic" sound. Before the diaphragm contracts, the roof of the mouth moves up, as does the back of the tongue, and there is often an associated burp. The heart slows a bit as well. In addition, hiccups are seldom isolated events but tend to recur every few seconds, sometimes for hours.
Together these observations imply that somewhere in the brain we have a "central pattern generator," or CPG, for hiccups. In other words, there is a neuronal circuit designed for generating hiccups similar to the ones we have for actions such as breathing, coughing and walking. And like most of those CPGs, it is an oscillator: it sends out a recurring, periodic signal to set off a hiccup. We don't have hiccups all the time, however, so the oscillator must be a "conditional oscillator" that fires only under certain conditions.
Hiccups are seen in a wide variety of animals and are very common in the fetus. They have been recorded physiologically in animal studies and are easily recognized on ultrasounds of human babies. Hiccups appear before breathing movements as the fetus develops and are common in newborns but gradually disappear over the next few months.
These observations suggest that hiccup CPG may be left over from a previous stage in evolution. Searching through the animal kingdom for a recurring, rhythmic activity that resembles a hiccup turns up a few candidates. None of them looks exactly like a hiccup, but that is not really surprising given all the changes that have occurred over the eons. One candidate is the CPG for gasping, which is a sudden inspiration and can be rhythmic. In a recent paper, my colleagues and I argued that a better candidate is the CPG used by tadpoles for gill ventilation. The unique feature of hiccups is a big inspiratory effort while closing the glottis, which completely blocks air from being inspired. Halfway through its development a tadpole has both lungs that breathe air and gills for breathing water. It does not have a diaphragm and cannot suck air into its lungs and instead pushes fluids with its mouth. To breathe air, it fills its mouth cavity with air, then closes its nose, mouth and the passage to the gills and compresses the mouth cavity, forcing the air into its lungs. To breathe water, it fills its mouth with water and then closes the glottis and forces the water out through the gills. The positive pressure pump action of the mouth is synchronous with filling the lung or pushing water through the gills. The gill-breathing tadpole is thus inspiring while closing the glottis, the same action as hiccuping.
Answer originally posted May 3, 2004.