Interaction between intra‐oral cinnamaldehyde and nicotine assessed by psychophysical and physiological responses

Abstract

Cinnamaldehyde and nicotine activate the transient receptor potential subtype A1 (TRPA1) channel, which may cause burning sensations. This study investigated whether cinnamaldehyde modulates nicotine-induced psychophysical and physiological responses in oral tissues. Healthy non-smokers (n = 22) received, in a randomized, double-blind, crossover design, three different gums containing 4 mg of nicotine, 20 mg of cinnamaldehyde, or a combination thereof. Assessments of orofacial temperature and blood flow, blood pressure, heart rate, taste experience, and intra-oral pain/irritation area and intensity were performed before, during, and after a 10-min chewing regime. Cinnamaldehyde increased the temperature of the tongue and blood flow of the lip, and was associated with pain/irritation, especially in the mouth. Nicotine increased the temperature of the tongue and blood flow of the cheek, and produced pain/irritation in the mouth and throat. The combination of cinnamaldehyde and nicotine did not overtly change the psychophysical or physiological responses. Interestingly, half of the subjects responded to cinnamaldehyde as an irritant, and these cinnamaldehyde responders reported greater nicotine-induced pain/irritation areas in the throat. Whether sensitivity to cinnamaldehyde can predict the response to nicotine-induced oral irritation remains to be determined. A better understanding of the sensory properties of nicotine in the oral mucosa has important therapeutic implications because pain and irritation represent compliance issues for nicotine replacement products.

A Comparison of Oral Sensory Effects of Three TRPA1 Agonists in Young Adult Smokers and Non-smokers

“…Interestingly, menthol alone evoked burning sensations and pain, albeit to a lower degree than nicotine, in approximately half of the study participants, and further, these participants reported more intense burning and irritation when menthol and nicotine were applied in combination (Nielsen et al, 2016 ). In a subsequent study, we found a similar result for cinnamaldehyde alone and in combination with nicotine (Jensen et al, 2016 ).…”

“…In contrast to menthol and nicotine, cinnamaldehyde is the most selective TRPA1 agonist, is known to produce burning sensations and pain (Namer et al, 2005 ) and is the aldehyde that gives cinnamon its taste. Contrary to expectations, our previous study showed cinnamaldehyde in combination with nicotine did not exert a synergistic effect on intra-oral burning or irritation intensities (Jensen et al, 2016 ). However, individuals responding to cinnamaldehyde as an irritant demonstrated larger areas of nicotine evoked irritation in the throat (Jensen et al, 2016 ).…”

“…Contrary to expectations, our previous study showed cinnamaldehyde in combination with nicotine did not exert a synergistic effect on intra-oral burning or irritation intensities (Jensen et al, 2016 ). However, individuals responding to cinnamaldehyde as an irritant demonstrated larger areas of nicotine evoked irritation in the throat (Jensen et al, 2016 ).…”

“…Participants and investigators were not able to differentiate between gums based on their smell and all gums were of comparable size, color (white) and shape similar to our previous studies (Jensen et al, 2016 ; Nielsen et al, 2016 ; see Supplemental Figure 1 ). The doses of menthol, nicotine, and cinnamaldehyde are based on our previous studies (Jensen et al, 2016 ; Nielsen et al, 2016 ) and are within the range of commercially available chewing gum and nicotine rehabilitation products. The solubility of nicotine is much higher than cinnamaldehyde and menthol, however the polacrilex gum technology allows for a more slow release of nicotine from the gum resin.…”

“…Although, menthol can evoke cooling sensations, it is commonly used as a surrogate model for cold hypoalgesia (Namer et al, 2005 ), and is often perceived as painful. Pain and the sensation of burning occur in association with nicotine application to the oral tissues (Hummel et al, 1992 ; Jensen et al, 2016 ; Nielsen et al, 2016 ) or skin (Gore and Chien, 1998 ). Unlike menthol, the perception of pain and burning are primarily mediated by activation of TRPA1 receptors (Talavera et al, 2009 ; Kichko et al, 2015 ).…”