Categories
Neuroscience

The Neuroscience Behind Hiccups

The quick gaps of air, amid a barrage of hiccups, is something that almost all of us can relate to. And while in evolution, hiccups haven’t been found to hold any significant value to survival, little is actually known about its pathophysiology, and what is its purpose. Learn more about the background, causes, and treatments of hiccups!

Abstract

The quick gaps of air, amid a barrage of hiccups, is something that almost all of us can relate to. Derived from the Latin word ‘singult’, that means ‘to catch one’s breath while sobbing’.  Hiccups are defined as the involuntary contractions of the diaphragm followed by the abrupt closure of the trachea, creating a ‘hic’ sound.  And while in evolution, hiccups haven’t been found to hold any significant value to survival, little is actually known about its pathophysiology, and what is its purpose. 

Background

Hiccups are clinically classified by duration, and can be divided into multiple categories:

  • Transient hiccups – A few minutes or seconds
  • Acute hiccups – Less than 48hrs
  • Persistent – Over 2 days
  • Intractable – Over a month
  • Idiopathic chronic hiccup (aka Diabolic hiccup) – recurring hiccup attacks over 1 month

While there haven’t been any big studies on the average duration of hiccups, most hiccups are transient and go unreported. The National Health Service in the United Kingdom says that hiccups should typically last a few minutes but it really varies from person to person.

Hiccups can be onset for a variety of reasons, laughter being one of the most common reasons. Other factors include extreme emotions (e.g. anxiety, stress and excitement), a sudden change in temperature,  eating and drinking too fast, spicy food,  drinking carbonated beverages or too much alcohol.  Hiccups may also be caused by brain tumours, vascular disorders or nerve damage. Sometimes hiccups can also be a symptom of an underlying medical disease such as -Parkinson’s Disease, strokes and ischemia.  

Causes

Whilst the mechanism behind hiccups isn’t fully understood, researchers have concluded that there is a neurological reflex arc associated with hiccups.  The reflex arc primarily consists of two parts: the vagus nerve, and the phrenic nerves sending signals from the brain to the diaphragm.  The vagus nerve extends from the medulla to the abdomen, and it conveys innate sensory signals that naturally fire in our CNS.  The phrenic nerves send these signals and electrical impulses from the brain to the diaphragm and intercostal muscles.  The neurological mechanisms behind hiccups are still very poorly understood thus for now is not concrete as it may not only be confined to the medulla but may also involve other parts of the central nervous system (CNS) located between the brainstem and spine.  Researchers assume that patients with chronic hiccuping are likely to have irritation involving this reflex arc such as signals being sent at the wrong times.  Neurotransmitters involved in the process of hiccup have so far been found to include dopamine) and gamma-aminobutyric acid (GABA).  This has been demonstrated as some psychiatric medications that are used to stabilise or modify levels of dopamine and GABA have been found to induce hiccuping.  An example would be Aripiprazole, which is used to stabilize dopamine and serotonin systems through dopamine receptors as well as baclofen, a GABA derivative, which is used to treat hiccup due to CNS tumours and chronic renal failure.

Newborns and infants are particularly prone to hiccups, as they spend roughly 15 minutes a day hiccuping.  Hiccups begin in the womb at around nine weeks.  Researchers found that contractions of the diaphragm from a hiccup triggers two large brain waves followed by a third.  Researchers suppose that as a baby hiccups, the brain may associate the sound of hiccups with the feel of the diaphragm contraction. Being one of the first processes for an infant to experience, a study by Whitehall et al. suggests that hiccuping is significant in the early development of multi-sensory brain connections and signalling.

Parkinson’s Disease

In one study twenty percent of parkinsonism (PD) patients had frequent hiccups. Even in some patients, PD was diagnosed after the occurrence of intractable hiccups. Replacement therapy with dopamine agonists in PD patients is considered to induce certain episodes of a hiccup, however, in others, hiccup may occur as the non-motor symptom of PD rather than a side effect of anti-PD treatment. The pathogenesis is believed to be related to the fact that dopamine agonists share a high affinity for dopamine receptors which may be involved in the hiccup reflex arc.  The drugs to block dopaminergic neurotransmission including chlorpromazine and metoclopramide may be employed in treating hiccup episodes

Treatments for Chronic Hiccuping

Many interventions and nonclinical “cures” for hiccuping have been passed down by word of mouth and experience such as breathing into a bag, holding breath, swallowing granulated sugar, drinking/gargling iced water, forceful traction of the tongue, biting lemon,, eyeball compression, fright etc.  While these remedies can be very convenient and less hazardous, their effectiveness to treat serious hiccups is highly questionable.

For example, gag reflex has long been used as an immediate remedy to treat hiccup.  A possible method of “curing” hiccups could include the regulation of rhythm at which the phrenic nerve operates.

Typically, in the clinical setting, hiccups are not usually the problem itself but is rather a symptom of an underlying problem, thus most cures targeting the root cause of hiccuping such as prokinetics being widely used to treat hiccups due to stomach distension.  Chlorpromazine is currently the only medication approved for hiccups by the US Food and Drug Administration, and for many years it was the primary drug used to treat hiccups.  It acts by targeting dopamine within the hypothalamus.  It has serious potential side effects, including that of- hypotension, urinary retention, glaucoma, and delirium. Initially used to control seizures in patients with epilepsy, vagus nerve stimulators are also the only piece of equipment approved by the FDA for treating hiccups. It sends rhythmic electrical impulses from the brain to the vagus nerve, which passes through the neck, within the reflex arc behind hiccups.  Even a left vagal blockade via nerve stimulation might be applied to stroke-related intractable hiccup after the failure of the phrenic nerve block.

Conclusion

Hiccups for the most part aren’t to be intimidated of, in fact are typically rather humorous.  But as with anything, too much of something can be indicative of much more going on behind the scenes, and this can be particularly applied with hiccups.  A lot of us will look past hiccuping for 5 minutes or so, and cure them with natural or remedies that we’ve tried and tested by past experiences, however,  for those that suffer from such a ‘comedic’ symptom and problem that is chronic hiccuping, there are, but still lacking, drugs and technologies out there that can hopefully help treat this issue.

Nara Ito, Youth Medical Journal 2020

References

Chang, F. Y., & Lu, C. L. (2012). Hiccup: mystery, nature and treatment. Journal of neurogastroenterology and motility, 18(2), 123–130. https://doi.org/10.5056/jnm.2012.18.2.123

Mayo Clinic. (2017, May 24). Hiccups – Symptoms and causes

https://www.mayoclinic.org/diseases-conditions/hiccups/symptoms-causes/syc-20352613

Genetic and Rare Diseases Information Center. (2020, 11 5). Chronic Hiccups.

https://rarediseases.info.nih.gov/diseases/6657/chronic-hiccups

Woelk C. J. (2011). Managing hiccups. Canadian family physician Medecin de famille canadien, 57(6), 672–e201.

Moretto, E. N., Wee, B., Wiffen, P. J., & Murchison, A. G. (2013). Interventions for treating persistent and intractable hiccups in adults. The Cochrane database of systematic reviews, 2013(1), CD008768. https://doi.org/10.1002/14651858.CD008768.pub2

Kohse, E. K., Hollmann, M. W., Bardenheuer, H. J., & Kessler, J. (2017). Chronic Hiccups: An Underestimated Problem. Anesthesia and analgesia, 125(4), 1169–1183. https://doi.org/10.1213/ANE.0000000000002289

Whitehead, K., Jones, L., Laudiano-Dray, M. P., Meek, J., & Fabrizi, L. (2019). Event-related potentials following contraction of respiratory muscles in pre-term and full-term infants. Clinical Neurophysiology, 130(12), 2216-2221.

By Nara Ito

Nara Ito is a student from London, England. She is interested in neurology, immunology, and genetics

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s