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A re-consideration of neural/receptor mechanisms in chemotherapy-induced nausea and vomiting: current scenario and future perspective

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Abstract

The neural mechanisms and the receptors behind the course of chemotherapy-induced nausea and vomiting (CINV) are well described and considered mechanistically multifactorial, whereas the neurobiology of nausea is not completely understood yet. Some of the anti-neoplastic medications like cisplatin result in biphasic vomiting response. The acute phase of vomiting is triggered mainly via the release of serotonin from the enterochromaffin (EC) cells in the gastrointestinal tract (GIT) and results in stimulation of dorsal vagal complex (DVC) of the vomiting center and the vomiting is initiated by downward communication to the gut via vagal efferents. Agonism of 5HT3 receptors is majorly involved in the mediation of the acute phase. Therefore, antagonists at 5HT3 receptors are effective in the management of acute-phase vomiting episodes. Likewise, Dopamine type 2 (D2) receptors, dopamine neurotransmitter, Muscarinic receptors (M3), GLP1 receptors, and histaminergic receptors (H1) are also implicated in the vomiting act as well. In continuation, Cannabinoid type 1 (CB1) receptors are also recommended and included in the guidelines as agonism of presynaptically located CB1 receptors inhibits the release of excitatory neurotransmitters responsible for vomiting initiation. The delayed phase involves the release of “Substance P” in the gut and results in the stimulation of neurokinin-1 (NK1) receptors centrally in the area postrema (AP) and nucleus tractus solitarius (NTS), subsequently the vomiting response. The current understanding is the existence of overlapping mechanisms of neurotransmitters, serotonin, dopamine, and substance P throughout the time course of CINV. Furthermore, the emetic neurotransmitters are released via calcium ion (Ca++)-dependent mechanisms, implicating the molecular targets of intracellular Ca++ signaling in emetic circuitry. The current review entails the neurobiology of nausea and vomiting induced by cancer chemotherapeutic agents and the recent approaches in the management.

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Abbreviations

AP:

Area postrema

AVP:

Arginine vasopressin

BBB:

Blood–brain barrier

CINV:

Chemotherapy-induced nausea and vomiting

CB1 :

Cannabinoid receptor type 1

CNS:

Central nervous system

CTZ:

Chemoreceptor trigger zone

CSF:

Cerebrospinal fluid

CTA:

Conditioned taste aversion

DVC:

Dorsal vagal complex

D1-4 :

Dopamine receptors type 1–4

DMV:

Dorsal motor nucleus of the vagus

D:

Dopamine

Dopac:

Dihydroxy phenylacetic acid

EC:

Enterochromaffin cells

GIT:

Gastrointestinal tract

GABA:

Gamma-aminobutyric acid

GLP1 :

Glucagon-like peptide type 1

HP:

Hypothalamus

LTCC:

L-type calcium ion channels

NMDA:

N-methyl d-aspartate receptor

NK1 :

Neurokinin receptor type 1

NTS:

Nucleus tractus solitarius

SP:

Substance P

5HT1 :

5-Hydroxy tryptamine receptor type 1

5HT3 :

5-Hydroxy tryptamine receptor type 3

5HT4 :

5-Hydroxy tryptamine receptor type 4

5HT7 :

5-Hydroxy tryptamine receptor type 7

5HT1A :

5-Hydroxy tryptamine receptor type 1A

5HT1B :

5-Hydroxy tryptamine receptor type 1B

5HT1D :

5-Hydroxy tryptamine receptor type 1D

Δ9-THC:

Delta-9-tetrahydrocannabinol

5HIAA:

5-Hydroxy indole acetic acid

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  1. Department of Pharmacy, Faculty of Sciences, University of Swabi, Anbar, Swabi, 23430, Khyber Pakhtunkhwa, Pakistan

    Ihsan Ullah

  2. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong

    Ihsan Ullah

  3. Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Dir (L), Chakdara, 18000, KP, Pakistan

    Muhammad Ayaz

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Ullah, I., Ayaz, M. A re-consideration of neural/receptor mechanisms in chemotherapy-induced nausea and vomiting: current scenario and future perspective. Pharmacol. Rep 75, 1126–1137 (2023). https://doi.org/10.1007/s43440-023-00514-z

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