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Hiccups: A new explanation for the mysterious reflex

Insights & Perspectives
Hiccups: A new explanation for the
mysterious reflex
Daniel Howes
The common hiccup is a ubiquitous
reflex; everyone experiences hiccups
innumerable times through life, but
unlike the other common reflexes like
sneezing (clearing material from the
nasal passages) and coughing (clearing
material from the airways) there is no
known physiologic advantage for the
common hiccup [1–4].
Rather than continuing as a vestigial
reflex whose purpose has evolved away,
I propose that the hiccup may be a sur-
prisingly complex reflex to remove air
from the stomachs of young suckling
The hiccup (or hiccough) is an ono-
matopoeic name that comes from the
sound made by the abrupt closure of
the vocal cords approximately 35 milli-
seconds after the forceful contraction of
the respiratory muscles. In the medical
literature, hiccups are referred to as ‘sin-
gultus’, although this term was origin-
ally used to describe the sharp intake of
breath often associated with long
periods of crying.
When hiccups continue for more
than 48 hours or occur frequently they
may be a sign of a serious disease. More
often they go unnoticed or are con-
sidered a minor annoyance that serves
no valuable purpose.
Hiccups seem to occur in most mam-
mals. They have been studied in cats,
rats, and rabbits [1, 5], and are often
observed in horses, dogs, and humans.
The rhythmic movement of hiccups can
be felt by pregnant mothers and seen on
ultrasound occurring in the fetus in
utero, before swallowing or respiratory
reflexes appear. The reflex is most
prevalent in newborns and they spend
as much as 2.5% of their time hiccup-
ping [2], it then diminishes in infancy
with occasional brief recurrences
through life [1]. There do not appear
to be documented observations of hic-
cups in reptiles, amphibians, or birds.
Much of what is known about the
anatomy of the hiccup reflex comes from
the study of pathological hiccups, which
can arise as a result of infection or malig-
nancy near the diaphragm, or from
lesions in the brain. Afferent signals come
from the distal esophagus, stomach, and
the abdominal side of the diaphragm and
travel as part of the phrenic nerve, the
vagus, and sympathetic (T6-T12) chain
branches. The afferent limb path is vari-
able between individuals, as is the degree
of stimulus required to initiate the reflex.
The central component of the reflex
lies in the medulla. Electrophysiological
studies as well as the pattern of muscle
contraction suggest that the center for
the hiccup reflex is entirely separate
from the pathways involved in rhythmic
breathing [6]. A series of patients
with lateral medullary infarction
(Wallenberg’s syndrome) and hiccups
suggest that middle level and dorsolat-
eral lesions can induce hiccups.
Once initiated, hiccups usually
occur at a rate of 4–60 per minute.
The frequency remains fairly constant
in the individual, but can be modified
by various conditions. Hiccups are sup-
pressed by elevations in serum carbon
dioxide [3] and can be triggered by gas-
tric distention, rapid eating, or drinking
carbonated beverages [1].
Efferent nerves travel from the hic-
cup center to the diaphragm, the exter-
nal intercostals, the scalene muscles,
glottic structures, and the esophagus.
The most significant muscle group
involved is the diaphragm, and several
studies have shown that hiccups are
often unilateral, involving only the left
hemi-diaphragm [7, 8].
The result is the activation of the
respiratory muscles more vigorously
than with normal respiration, followed
approximately 35 milliseconds later by
closure of the glottis [3]. This forceful
inhalation effort against the closed glot-
tis leads to a sharp reduction in intra-
thoracic pressure. At the same time,
normal esophageal peristalsis is sup-
pressed and the lower-esophageal
sphincter relaxes. Innervation to the
muscles of exhalation is inhibited.
The drop in intra-thoracic pressure
is experienced by the lungs, the heart,
and great vessels, lymphatic vessels, the
thymus, and the esophagus where it
traverses the thorax. The stomach lies
DOI 10.1002/bies.201100194
Queen’s University Department of Emergency
Medicine, Kingston, Ontario, Canada
Corresponding author:
Daniel Howes
Bioessays 34: 451–453,ß2012 WILEY Periodicals, Inc. 451
Ideas & Speculations
underneath the diaphragm and is out-
side the thoracic cavity.
Previous theories of why
we hiccup
A hypothesis seeking to explain the pur-
pose of the hiccup should meet the fol-
lowing criteria in order to be considered
1. The hypothetical stimulus of the hic-
cup should be anatomically consistent
with the afferent limb of the reflex.
2. The activation of the efferent limb of
the reflex should resolve or help to
resolve the condition that leads to the
stimulus. Ideally the condition
should explain all of the components
of the efferent limb.
3. The hypothesis should offer an
explanation for the hiccup’s preva-
lence in mammals and its profoundly
increased incidence during infancy.
4. The resolution of the condition that is
hypothesized to stimulate the hiccup
should offer a tangible evolutionary
Many purposes have been proposed
for the hiccup, but to date none has met
all four of the criteria above.
Suggestions that hiccup represent a
form of epilepsy [9] or a failure of supra-
spinal inhibition [10] may suggest
causes for pathological hiccups, but
they do not explain the presence of
the reflex in the normal individual.
Similarly, the suggestion that the hiccup
could be a dysfunction of the reciprocal
inhibition of an inspiratory effort related
to breathing and a simultaneous glottic
closure related to swallowing [11] fails to
explain the afferent limb of the reflex.
Furthermore, hiccups are often present
in the absence of swallowing.
In 1899, Ferroni suggested that hic-
cups were a form of preparation for the
fetus to strengthen the muscles involved
in respiration, a hypothesis more recently
revisited by Kahrilas and Shi [2]. The
respiratory exercise hypothesis does not
explain the existence of the afferent limb
of the reflex. Furthermore, the brief con-
traction of the respiratory muscles is
unlikely to have any beneficial effect on
respiratory muscles, which have a high
concentration of slow twitch fibers for
Other suggestions related to fetal devel-
opment have included clearance of
meconium (the first feces that a newborn
produces; in times of fetal distress meco-
nium can be passed while in the uterus
and then breathed in) and training for
suckling, but these do not seem plausible
in light of the actions of the reflex. The
strong contraction of the respiratory
muscles would move meconium deeper
into the airway, and the majority of the
muscles triggered by the hiccup reflex are
not involved in suckling.
Straus et al. [1] proposed a phylo-
genic hypothesis that the hiccup is an
evolutionary remnant that originated
with gill ventilation. They make an
excellent argument for the phylogenic
development of the hiccup reflex from
ventilatory motor patterns of lower
vertebrates and suggest that the hiccup
is an evolutionary remnant. This hy-
pothesis – that there is no purpose for
the hiccup – should only be accepted in
the absence of an acceptable expla-
nation for its evolutionary persistence.
Others have suggested that the hic-
cup is a reflex to move boluses of food
trapped in the esophagus [4]. This
theory is supported by the afferent
innervation of the reflex, suggesting
that the stimulus is a condition sensed
in the area of the lower esophagus,
stomach, or beneath the diaphragm. It
would also explain the simultaneous
relaxation of the lower-esophageal
sphincter. The main problem with this
theory is that the action of the hiccup
would move a food bolus toward the
middle of the chest – a food bolus in
the lower esophagus would move away
from the stomach where it can be safely
digested and toward the airway, where
it could become a dangerous obstruc-
tion. The fact that patients who present
with food stuck in the esophagus rarely
have associated hiccups and the high
prevalence of hiccups in suckling new-
borns who do not consume solids, do
not support this hypothesis.
The most notable action of
the hiccup reflex is the
sharp drop in intra-thoracic
The closure of the glottis with strong
contraction of the respiratory muscles
results in a sharp drop in the intra-
thoracic pressure, which suggests that
the purpose of this reflex is to move
something from outside of the thoracic
cavity toward the inside. There are five
conduits between the intra- and extra-
thoracic areas that contain fluid or air
that might be moved, namely arterial,
venous, and lymphatic vessels, the tra-
chea, and the esophagus.
pressure flow that would be expected to
change very little as a result of the brief
action of a hiccup. Venous and lym-
phatic flow may be somewhat increased
by the action of the hiccup, but it is
unlikely that it is significantly changed
by such a brief stimulus. In addition to
that, stimuli in the area of the afferent
limb are unlikely to be resolved by the
impact on blood or lymph flow.
A number of the previously offered
explanations for the hiccup suggest the
trachea as the conduit of interest, but
this seems unlikely. The rapid closure of
the glottis serves to prevent most of the
air movement through the trachea,
movement that could be much greater
if the timing were different. Foreign
material partially obstructing the airway
would be moved deeper into the airway
by a hiccup, thereby impeding clear-
ance. Moreover, the airway is already
well protected by gag, cough, and
sneeze reflexes, the afferent limbs of
which are more appropriately situated.
This leaves the esophagus. The
negative intra-thoracic pressure of the
hiccup would move material from
the mouth or the stomach toward the
mid-section of the esophagus. The
existence of the swallowing reflex for
moving material from the mouth, as
well as the anatomy of the afferent limb,
suggest the purpose of the hiccup
relates to the lower esophagus instead
of the upper esophagus or mouth.
The contents of the stomach are
the materials of digestion and gas. The
vomiting reflex effectively removes
unwanted materials of digestion, leav-
ing stomach gas as the potential trigger
for physiologic hiccups.
The hiccup as a burping
Is it possible that the hiccup functions
to remove swallowed gas from the
D. Howes Insights & Perspectives.....
452 Bioessays 34: 451–453,ß2012 WILEY Periodicals, Inc.
Ideas & Speculations
stomach – essentially an evolved
burping reflex? The presence of an air
bubble in the stomach or distal esoph-
agus could stimulate mechanoreceptors
that activate the afferent limb of the
reflex (Fig. 1A). The contraction of
the respiratory muscles and closure of
the glottis would drop the intra-thoracic
pressure (Fig. 1B), pulling the air from
the stomach in to the mid-esophagus
(Fig. 1C), where it could then leave
through the mouth with the next
exhalation. This explanation is sup-
ported by the suppression of esophageal
peristalsis and the relaxation of the
lower esophageal sphincter that are
part of the reflex.
The presence of a burping reflex pro-
vides a significant survival advantage.
Young mammals depend on milk
consumption for their nutrition. The
continuous nature of suckling means
that it has to be coordinated with
respiration and the result can be
swallowed air. A reflex that helps
remove swallowed air would signifi-
cantly increase the stomach’s capacity
for milk. This also explains why the
hiccup is so much more frequent in
If this hypothesis is true, there must
be something about the presence of air
in the stomach that can be differentiated
from distention with food. A future test
of the hypothesis could be to identify
how the reflex differentiates air; either
directly or from a pattern of stimuli that
occurs with the movement of an air
The hiccup is a very common reflex. I
propose that hiccups are triggered by
the presence of air in the stomach.
This stimulates the sharp intake
typical of the reflex, moving swallowed
air out of the stomach and effectively
‘burping’ suckling infants, allowing
them to consume a greater volume of
milk in the meal. For adults, the infre-
quent annoying affliction reflects per-
sistence of an infantile reflex and a
reminder that we may have eaten too
Figure 1. The hiccup may have evolved to remove air from the stomachs of young suckling
mammals. A: The presence of air (yellow) in the stomach beneath the diaphragm triggers the
afferent limb of the reflex, sending signals to the medulla (shown in red). B: Activation of the
reflex efferent limb (purple) causes the muscles of respiration to expand the chest (green
arrows), while simultaneously closing the opening of the trachea (green X). The result is a
sharp drop in pressure in the chest (symbolized by ). C: The negative intra-thoracic pressure
moves the air bubble to the thoracic esophagus. With relaxation after the hiccup, the air can
pass up the esophagus and out the mouth, leaving more room for milk.
There is, as yet, no proof for this hy-
pothesis, but hopefully it will stimulate
some thought about this ubiquitous
unexplained reflex, and provide a
framework for exploring its anatomy
and physiology in greater detail.
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3. Lewis JH. 1985. Hiccups: causes and cures.
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4. Fass R,Higa L,Kodner A,Mayer EA. 1997.
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6. Davis JN. 1970. An experimental study of
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7. Samuels L. 1952. Hiccup: a ten year review of
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8. Salem MR,Baraka A,Rattenborg CC,
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.....Insights & Perspectives D. Howes
Bioessays 34: 451–453,ß2012 WILEY Periodicals, Inc. 453
Ideas & Speculations
... Hıçkırık hayatı direkt anlamda tehdit etmese bile kişilerde; depresyon, uykusuzluk, yetersiz beslenme ve bitkinlik ile beraber yaşam kalitelerinde hızlı bir düşüşe neden olabilir (Hosaya ve ark., 2017). Hıçkırık atakları; genellikle aşırı yemek yemeye, asitli içeceklerin aşırı tüketimine, aerofajiye (aşırı ve tekrarlı hava yutmaya) ve endoskopi esnasında mideye hava verilmesine bağlı olarak oluşan gastrik distansiyonla ortaya çıkabilir (Howes D., 2012). Diğer sebepler arasında; çevresel ya da gastrointestinal ısının ani değişiklikleri, aşırı alkol alımı, ani heyecan veya diğer emosyonel stresler sayılabilir. ...
... Afferent impuls vagus siniri, frenik sinirler veya sempatik sinir lifleri tarafından taşınır. Hıçkırık yanıtında yer alan santral sinir sistemi bölgeleri, üst omuriliği (C3-C5), solunum merkezinin yakınındaki medulla oblongatadaki beyin sapını, retiküler oluşumu ve hipotalamusu kapsıyor gibi görünmektedir (Howes, 2012). Dopaminerjik ve gama-amino-butirik-asit (GABA-ergic) nörotransmiterler bu merkezi mekanizmayı modüle edebilir (Eisenacher ve Spiske, 2011). ...
... Vagus sinir stimulasyon yöntemi inatçı idiyopatik hıçkırıklarda etkili olmayabilir (Gravel ve ark., 2018). Ayrıca vagal stimülasyonun, depresyon, kardiyovasküler, serebrovasküler, metabolik biyobelirteçler üzerinde potansiyel olarak olumlu etkileri vardır (Howes, 2012). ...
... to the hiccup rhythm centre in the Pre-Botzinger complex, nucleus ambiguous, lateral reticular nucleus, hypothalamus and mesial temporal lobes [2][3][4][5]. Gama-Aminobutyric Acid (GABA) and dopamine act as neurotransmitters for this refl ex. ...
... The vagus nerve forms a signifi cant component of the hiccup refl ex arc and can explain several odd triggers as well as the basis for most initial remedies [4,9,10]. In fact hiccups most frequently occur during inspiration when lung infl ation impedes vagal afferents known to suppress hiccups [6]. ...
... In fact hiccups most frequently occur during inspiration when lung infl ation impedes vagal afferents known to suppress hiccups [6]. The vagus nerve, also referred to as the ''wandering'' nerve or the ''vagabond'' nerve, greatly innervates multiple organs of the body and forms a part of several bodily refl exes [4,7,10]. Its stimulation has demonstrated varied functional outcomes the exact mechanism of most of which are not clearly understood [7]. ...
... Hiccups are sounds produced by sudden involuntary contraction of the diaphragm and intercostal muscle followed by abrupt closure of the glottis [1,2]. Hiccups are a common occurrence in most mammals including cats, rats, horses, and humans, and are a reflex mechanism that might remove air from the stomach of suckling young [3]. More common in men, hiccups are often benign and self-limiting [4]. ...
... Persistent hiccups last for approximately 48 hours, while intractable hiccups usually last longer than one to two months. The exact mechanism of hiccups remains complex and poorly understood, but a reflex arc involving the peripheral phrenic, vagal, and sympathetic pathways, in addition to multiple neurotransmitters seem to play a role in hiccups [1][2][3]. ...
Full-text available
Hiccups, involuntary contraction of the diaphragm and intercostal muscle followed by an abrupt closure of the glottis, are a bothersome symptom that can be caused by a variety of illnesses or medications. Hiccups that persist for more than 48 hours should raise the suspicion of an underlying cause. Pneumonias, especially caused by the novel coronavirus, have rarely been reported to trigger hiccups. To the best of our knowledge, we present the first case in sub-Saharan Africa of a patient presenting to our institution with persistent hiccups and no other objective signs suggestive of underlying pneumonia. His high-resolution CT was suggestive of coronavirus disease 2019 (COVID-19) and a polymerase chain reaction (PCR) test confirmed the diagnosis. Our case highlights the need for a thorough history and physical examination in patients presenting with hiccups and the need to include COVID-19 in the differential diagnosis in such patients.
... The hiccup reflex arc is constituted by an afferent limb formed by the phrenic, vagus, and the sympathetic chains, central unit in the medulla and the efferent limb formed by the phrenic nerve again which is responsible for the contraction of the respiratory muscle. 1 A hiccup when lasts for more than 48 hours is termed "persistent" and for more than a month is termed "intractable" and often these incessant ones speak for an underlying serious disease. There are over 100 different associations related to these pathological hiccups; from the most common causes like the reflux oesophagitis and cerebrovascular disease to the less common causes like Ebola virus disease. ...
... The irritation from the infarct or ischemic area may result in stimulation of these fires and cause hiccups. Also, irritation of phrenic nerves, which innervates the diaphragm, can cause persistent hiccups in those patients [13]. Therefore, physicians shall consider the extension of infarction to the inferior wall if a patient with an otherwise stable myocardial infarction develops hiccups [14]. ...
Background: Hiccups are benign and self-limited condition, but attention should be paid to the underlying conditions when persist. There are various causes of persistent hiccups, including metabolic abnormalities, psychogenic disorders, malignancy, nervous system pathology, medications, pulmonary disorders, or gastrointestinal etiologies. It is rarely attributed to cardiac disease. Case Summary: We report a case of intractable hiccups in a 67 y/o male as the initial symptom of coronary heart disease. He presented with a few-week history of hiccups and no other complaints. Echocardiography demonstrated wall motion abnormalities in the left ventricle with severe impairment of systolic function. He was He was admnistered chlorpromazine and anti-ischemic treatment, and a thallium viability study was advised before cardiac catheterization to confirm viable or nonviable myocardium. He refused further evaluation and was discharged with appropriate care. The gentleman was readmitted for heart failure two weeks after discharge due to poor medication adherence. The delay in treatment had affected his chances of survival, and his hiccuping symptoms had recurred and persisted. Finally, he died after two months from the time of diagnosis. Discussion: This case makes highlights the importance of having a high index of suspicion, especially in elderly diabetic patients where benign self-limiting conditions like hiccups can only present symptoms of severe cardiac disease. Cardiac disease should be considered even when the symptoms are only gastrointestinal; simple investigations in the form of changes in electrocardiogram with cardiac enzyme elevation may disclose the cardiac findings, as they did in our case!
... Only postnatally, these behaviours are accompanied by characteristic breath-sounds: yawns produce a sound generated by the inhalation and exhalation of air, while hiccups produce the typical hic sound generated by the contraction of the diaphragm. It is also important to note that both yawns and hiccups possess fundamental functions in humans: yawning is considered a communicative behaviour (Guggisberg et al., 2010), while hiccup, which is a primitive and common motor behaviour in utero and in newborn infants, is considered crucial for the maturation of the inspiratory muscles and for nutrition (Howes, 2012;Kahrilas & Shi, 1997). ...
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Already inside the womb, fetuses frequently bring their hands to the mouth, anticipating hand-to-mouth contact by opening the mouth. Here, we explored whether 2-day-old newborns discriminate between hand actions directed towards different targets of the face – i.e., a thumb that reaches the mouth and a thumb that reaches the chin. Newborns looked longer towards the thumb-to-mouth compared to the thumb-to-chin action only in the presence, and not absence, of anticipatory mouth opening movements, preceding the thumb arrival. Overall, our results show that newborns are sensitive to hand-to-face coordinated actions, being capable to discriminate between body-related actions directed towards different targets of the face, but only when a salient visual cue that anticipates the target of the action is present. The role of newborns’ sensorimotor experience with hand-to-mouth gestures in driving this capacity is discussed. This article is protected by copyright. All rights reserved
... Only postnatally, these behaviours are accompanied by characteristic breath-sounds: yawns produce a sound generated by the inhalation and exhalation of air, while hiccups produce the typical hic sound generated by the contraction of the diaphragm. It is also important to note that both yawns and hiccups possess fundamental functions in humans: yawning is considered a communicative behaviour (Guggisberg et al., 2010), while hiccup, which is a primitive and common motor behaviour in utero and in newborn infants, is considered crucial for the maturation of the inspiratory muscles and for nutrition (Howes, 2012;Kahrilas & Shi, 1997). ...
Multisensory experiences crucially contribute to the development of infants’ ability to match audio-visual (A-V) information. This study investigated two-day-old newborns’ ability to bind non-verbal, naturally occurring, experienced A-V stimuli. Our results demonstrate that, when presented with experienced stimuli (yawns and hiccups) within an intermodal matching procedure, 2-days-old newborns matched not only synchronous (Experiment 1) but also asynchronous A-V information (Experiment 2). Conversely, no evidence of A-V association was found when unexperienced stimuli, such as a linguistic sound (syllable/ba/) (Experiment 3), were presented in asynchrony. The possible role of sensorimotor experience in the early emergence of intersensory abilities is discussed.
... An individual's hiccup rate is usually consistent for each hiccup episode, occurring at a frequency of 4 to 60 hiccups per minute [7,8]. The classification of hiccups is by their duration: acute hiccups or "hiccup bouts" are of less than 48-hour duration, persistent lasts over 2 days, and intractable lasts over a month [9]. ...
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Hiccups are sudden, repeated, and involuntary contractions of the diaphragm muscle (myoclonic contraction). It involves a reflex arc that, once activated, causes a strong contraction of the diaphragm immediately followed by the closure of the glottis translating into the classic "hic" sound. Hiccups can be short, persistent, and intractable depending on the duration. The most disabling hiccups often represent the epiphenomenon of a medical condition such as gastrointestinal and cardiovascular disorders; central nervous system (CNS) abnormalities; ear, nose, and throat (ENT) conditions or pneumological problems; metabolic/endocrine disorders; infections; and psychogenic disorders. Some drugs, such as aripiprazole, a second-generation antipsychotic, can induce the onset of variable hiccups. We describe herein the cases of three hospitalized patients who developed insistent hiccups after taking aripiprazole and who positively responded to low doses of gabapentin. It is probable that aripiprazole, prescribed at a low dosage (<7.5 mg/day), would act as a dopamine agonist by stimulating D2 and D3 receptors at the "hiccup center" level-located in the brain stem-thus triggering the hiccup. On the other hand, gabapentin led to a complete regression of the hiccup probably by reducing the nerve impulse transmission and modulating the diaphragmatic activity. The present case series suggests the use of low doses of gabapentin as an effective treatment for aripiprazole-induced hiccups. However, our knowledge of the neurotransmitter functioning of the hiccup reflex arc is still limited, and further research is needed to characterize the neurotransmitters involved in hiccups for potential novel therapeutic targets.
In diesem Kapitel untersuchen wir den Verlauf der pränatalen Entwicklung – einer Zeit erstaunlich schnellen und dramatischen Wandels. Wir werden Störeinflüsse und Umweltgefahren, die den sich entwickelnden Fötus schädigen können, betrachten. Danach behandeln wir in Kürze den Prozess der Geburt und besondere Verhaltensaspekte des Neugeborenen. Schließlich diskutieren wir Probleme, die mit geringem Geburtsgewicht und Frühgeburt einhergehen.
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Background Hiccups is a known presentation of lateral medullary infarction. However, the region in the medulla associated with this finding is not clearly known. In this study, we aimed to study the neural correlates of hiccups in patients with lateral medullary infarction (LMI). Materials and Methods This retrospective study included all patients who presented with lateral medullary infarction between January 2008 and May 2018. Patients with hiccups following LMI were identified as cases and those with no hiccups but who had LMI were taken as controls. The magnetic resonance imaging of the brain was done viewed and individual lesions were mapped manually to the template brain. Voxel-based lesion-symptom mapping employing nonparametric permutation testing was performed using MRIcron. Results There were a total of 31 patients with LMI who presented to the hospital during the study period. There were 11 (35.5%) patients with hiccups. Using the voxel-based lesion-symptom mapping analysis, the dorso-lateral region of the middle medulla showed significant association with hiccups. Conclusion In patients with LMI, we postulate that damage to the dorsolateral aspect on the middle medulla could result in hiccups.
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See article on page 590 Considering the fact that almost everyone experiences hiccups at one time or another, remarkably little is known about them. The name itself is onomatopoeic, which is appropriate considering that the only common understanding of the hiccup is of the characteristic sound. Hiccups can be predictably elicited in some individuals by overindulgence of food, alcohol, or both, sometimes providing evidence of such behaviour and making them a common object of humour. There are, however, instances in which hiccups become intractable (singultus) causing insomnia, wasting, exhaustion, and even death, prompting scientific scrutiny of this otherwise harmless curiosity.1In this issue Fass et al (see page 590) present original investigative work on the afferent limb of the hiccup reflex. Fass et al used a barostat to characterise the parameters of oesophageal distention that could elicit hiccups in normal volunteers. They report that rapid phasic distension of the proximal, but not distal, oesophagus could reproducibly induce hiccups in four of 10 subjects. Hiccups occurred during rapid inflation of the barostat bag and immediately resolved with deflation, strongly implicating oesophageal mechanoreceptors as the critical …
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Hiccups that are induced by a large meal have been suggested to result from gastric overdistension. The role of the oesophagus in precipitating hiccups has never been defined. To determine the involvement of oesophageal mechanoreceptors in the hiccup reflex. Ten normal healthy subjects were prospectively evaluated at a university affiliated hospital. Controlled inflation of a polyethylene bag in the proximal and distal oesophagus was carried out using slow ramp and rapid phasic distensions, by an electronic distension device. Hiccups were induced in four subjects only during rapid phasic distensions and only in the proximal oesophagus. The mean (SEM) minimal volume threshold for the hiccup reflex was 32.5 (4.8) ml, which was above the perception threshold. Hiccups appeared during inflation and resolved after deflation. Sudden rapid stretch of the mechanoreceptors in the proximal oesophagus can trigger the hiccup reflex in normal subjects. Only rapid distensions above a determined volume threshold will predictably induce hiccups in a given subject. This mechanism may play a role in the physiological induction of hiccups.
In three patients, intractable hiccups occurred as part of the symptomatology of multiple sclerosis. In one patient intractable hiccups were the presenting complaint, and in another patient exacerbations of symptoms were almost always heralded by intractable hiccups. Intractable hiccups occur in a variety of diseases, including many that affect the brainstem and cervical cord, but have not been reported in multiple sclerosis. The hiccup may be a "primitive" gastrointestinal reflex that is disinhibited by lesions such as multiple sclerosis plaques. Carbamazepine was successful in arresting the hiccups in one of the cases presented.
Every new empiric observation made over two millenia fueled the dispute as to whether hiccup (Hc) is a digestive or a respiratory reflex. A review of the literature, focusing attention on the probable mechanism of Hc, shows Hc as a neurogenic dysfunction of the 'valve function' between the inspiratory complex and the glottis closure complex.
Hiccups result from a wide variety of conditions that act on the supraspinal hiccup center or that stimulate or disinhibit the limbs of its reflex arc. While scores of hiccup remedies have been reported over the centuries, no single "cure" stands out as being the most effective. Measures that stimulate the uvula or pharynx or disrupt diaphragmatic (respiratory) rhythm are simple to use and often help to speed the end of a bout of otherwise benign, self-limited hiccups. Such manueuvers may also terminate persistent hiccups. Drug therapy usually becomes necessary for more intractable hiccups; chlorpromazine and metoclopramide being two of the most widely employed agents for this purpose. Physical disruption of the phrenic nerve, hypnosis, and acupuncture are other modes of therapy that have been used in severe cases. Because so many reports of hiccup "cures" are based on anecdotal experience rather than controlled clinical studies, I review the available treatments to provide a rational approach for the management of hiccups.
Stimulation of the pharynx with a catheter introduced through the nose appears to be a valuable method for managing hiccups in conscious and anesthetized man. Immediate inhibition of hiccups occurred in 84 of 85 patients treated in this manner, of whom 65 were anesthetized. Hiccups recurred in some patients, but were successfully managed with the same maneuver. The area responding to stimulation is the middle of the pharynx, opposite the body of the second cervical vertebra, which is innervated by the pharyngeal plexus. The suggested mechanism of action is impulses arising in response to pharyngeal stimulation which may block or inhibit afferent impulses being transmitted through the vagi thus interrupting the hiccup reflex. No undesirable effects have been encountered as a result of pharyngeal stimulation.
To identify the site for triggering hiccup, we recorded activities from the diaphragm (DIA), posterior cricoarytenoid muscle (PCA) of the larynx, and abdominal muscle (ABD) along with intrapleural pressure (Ppl) in anesthetized spontaneously breathing cats. To directly access the epipharynx and to observe glottic movement, we made a submental opening at the level rostral to the epiglottis. Mechanical stimulation of the epipharynx evoked a fixed motor pattern of hiccup: DIA showed spasmodic discharge, and Ppl exhibited spiky negative pressure swing; phasic (inspiratory) discharge of PCA was inhibited, and glottic adduction was revealed by direct observation; and ABD remained suppressed during this response. Chlorpromazine hydrochloride or CO2 inhalation suppressed the response, and the intensity of the response varied according to phase of the respiratory cycle, being largest at midinspiration and least at midexpiration. These are compatible with clinical data on human hiccup. Mechanical stimulation of various parts other than the epipharynx failed to evoke the hiccuplike response. The triggering site was located in the dorsal wall of the epipharynx overlying the occipital bone. These results indicate that mechanical irritation of the dorsal epipharynx is essential for triggering hiccup.
Hiccup is a forceful, involuntary inspiration commonly experienced by fetuses, children and adults. Its purpose is unknown and its pathophysiology still poorly understood. Short hiccup bouts are mostly associated with gastric distention or alcohol intake, resolve spontaneously or with simple folk remedies and do not require medical attention. In contrast, prolonged hiccup is a rare but disabling condition which can induce depression, weight loss and sleep deprivation. A wide variety of pathological conditions can cause chronic hiccup: myocardial infarction, brain tumour, renal failure, prostate cancer, abdominal surgery etc. Detailed medical history and physical examinations will often guide diagnostic investigations (abdominal ultrasound, chest or brain CT scan...). Gastric and duodenal ulcers, gastritis, oesophageal reflux and oesophagitis are commonly observed in chronic hiccup patients and upper gastrointestinal investigations (endoscopy, pH monitoring and manometry) should be included in the diagnostic evaluation systematically. Etiological treatment is not always available and chronic hiccup treatment has classically relied on metoclopramide and chlorpromazine. Recently, baclofen (LIORESAL) has emerged as a safe and often effective treatment.
The occurrence of hiccoughs (hiccups) is very widespread and yet their neuronal origin and physiological significance are still unresolved. Several hypotheses have been proposed. Here we consider a phylogenetic perspective, starting from the concept that the ventilatory central pattern generator of lower vertebrates provides the base upon which central pattern generators of higher vertebrates develop. Hiccoughs are characterized by glottal closure during inspiration and by early development in relation to lung ventilation. They are inhibited when the concentration of inhaled CO(2) is increased and they can be abolished by the drug baclofen (an agonist of the GABA(B) receptor). These properties are shared by ventilatory motor patterns of lower vertebrates, leading to the hypothesis that hiccough is the expression of archaic motor patterns and particularly the motor pattern of gill ventilation in bimodal breathers such as most frogs. A circuit that can generate hiccoughs may persist in mammals because it has permitted the development of pattern generators for other useful functions of the pharynx and chest wall muscles, such as suckling or eupneic breathing.