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Papers of the Week

2021 May 06

Nicotine Tob Res

Sensory effects of nicotine and tobacco.


Carstens E E, Carstens IM
Nicotine Tob Res. 2021 May 06.
PMID: 33955474.


Ingestion of nicotine by smoking, vaping or other means elicits various effects including reward, antinociception, and aversion due to irritation, bitter taste and unpleasant side effects such as nausea and dizziness. Here we review the sensory effects of nicotine and the underlying neurobiological processes. Nicotine elicits oral irritation and pain via the activation of neuronal nicotinic acetylcholine receptors (nAChRs) expressed by trigeminal nociceptors. These nociceptors excite neurons in the trigeminal subnucleus caudalis (Vc) and other brainstem regions in a manner that is significantly reduced by the nAChR antagonist mecamylamine. Vc neurons are excited by lingual application of nicotine and exhibit a progressive decline in firing to subsequent applications, consistent with desensitization of peripheral sensory neurons and progressively declining ratings of oral irritation in human psychophysical experiments. Nicotine also elicits a nAChR-mediated bitter taste via excitation of gustatory afferents. Nicotine solutions are avoided even when sweeteners are added. Studies employing oral self-administration have yielded mixed results: some studies show avoidance of nicotine while others report increased nicotine intake over time, particularly in adolescents and females. Nicotine is consistently reported to increase human pain threshold and tolerance levels. In animal studies, nicotine is antinociceptive when delivered by inhalation of tobacco smoke or systemic infusion, intrathecally, and by intracranial microinjection in the pedunculopontine tegmentum, ventrolateral periaqueductal gray and rostral ventromedial medulla. The antinociception is thought to be mediated by descending inhibition of spinal nociceptive transmission. Menthol cross-desensitizes nicotine-evoked oral irritation, reducing harshness that may account for its popularity as a flavor additive to tobacco products.