Neurotransmitters in hiccups

Abstract

Hiccups are the sudden involuntary contractions of the diaphragm and intercostal muscles. They are generally benign and self-limited, however, in some cases they are chronic and debilitating. There are approximately 4000 admissions for hiccups each year in the United States. The hiccup reflex arc is composed of three components: (1) an afferent limb including the phrenic, vagus, and sympathetic nerves, (2) the central processing unit in the midbrain, and (3) the efferent limb carrying motor fibers to the diaphragm and intercostal muscles. Hiccups may be idiopathic, organic, psychogenic, or medication-induced. Data obtained largely from case studies of hiccups either induced by or treated with medications have led to hypotheses on the neurotransmitters involved. The central neurotransmitters implicated in hiccups include GABA, dopamine, and serotonin, while the peripheral neurotransmitters are epinephrine, norepinephrine, acetylcholine, and histamine. Further studies are needed to characterize the nature of neurotransmitters at each anatomical level of the reflex arc to better target hiccups pharmacologically.

Tramadol-Induced Hiccups: A Report of Two Cases

“…Although the exact mechanism by which hiccups develops is poorly understood, a central component of the hiccups reflex arc is situated in the medulla. Serotonin, dopamine, γ-aminobutyric acid (GABA), glutamate, and glycine neurotransmitters can regulate this central mechanism of hiccups [ 1 ]. This reflex arc is also regulated by input from catecholaminergic and serotonergic afferents.…”

“…Hiccups (singultus) are the involuntary and rapid expulsion of air from the lungs with the asynchronous closure of the glottis, causing disruption of the flow of air. They can be acute (< 48 h), enduring (> 48 h) or persistent (> 1 month) [ 1 ]. Hiccups caused by distention of the stomach, stress, rapid change in temperature, and alcohol intake are generally benign and self-limiting.…”

“…They can be due to an underlying pathology or can have an organic cause, and, if left untreated, can be serious. Hiccups are modulated by a reflex arc with afferents, including the vagus, phrenic nerve and sympathetic chain; a central hiccup center, including the respiratory center, phrenic nerve nuclei, and reticular part of the hypothalamus; and efferent, which includes the phrenic nerve, glottis, and nerves to the intercostal muscles [ 1 ]. Drug-induced hiccups are a rare entity and diagnosis requires exclusion of other causes.…”

“…Nausea, vomiting, constipation, sweating, dry mouth, headache, lower leg edema, swelling in the face or tongue, rhinorrhoea, dry skin, and burning in the eyes are the most frequently occurring adverse drug reactions. Respiratory depression only occurs when high doses of tramadol, or concomitant drugs with centrally inhibiting effects, are used [ 1 ]. However, the incidence of tramadol-induced hiccups is rare.…”

Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database

“…Previous studies investigated hiccups-related drugs [ 8 – 12 ]. Fauzia Nausheen et al described the following about the neurotransmitters related to hiccups in their review [ 13 ]. The reflex arc is potentially mediated by central neurotransmitters (GABA, dopamine, and serotonin) and peripheral neurotransmitters (epinephrine, norepinephrine, acetylcholine, and histamine).…”