Modulation of Oral Heat and Cold Pain by Irritant Chemicals

Abstract

Common food irritants elicit oral heat or cool sensations via actions at thermosensitive transient receptor potential (TRP) channels. We used a half-tongue, 2-alternative forced-choice procedure coupled with bilateral pain intensity ratings to investigate irritant effects on heat and cold pain. The method was validated in a bilateral thermal difference detection task. Capsaicin, mustard oil, and cinnamaldehyde enhanced lingual heat pain elicited by a 49 degrees C stimulus. Mustard oil and cinnamaldehyde weakly enhanced lingual cold pain (9.5 degrees C), whereas capsaicin had no effect. Menthol significantly enhanced cold pain and weakly reduced heat pain. To address if capsaicin's effect was due to summation of perceptually similar thermal and chemical sensations, one-half of the tongue was desensitized by application of capsaicin. Upon reapplication, capsaicin elicited little or no irritant sensation yet still significantly enhanced heat pain on the capsaicin-treated side, ruling out summation. In a third experiment, capsaicin significantly enhanced pain ratings to graded heat stimuli (47 degrees C to 50 degrees C) resulting in an upward shift of the stimulus-response function. Menthol may induce cold hyperalgesia via enhanced thermal gating of TRPM8 in peripheral fibers. Capsaicin, mustard oil, and cinnamaldehyde may induce heat hyperalgesia via enhanced thermal gating of TRPV1 that is coexpressed with TRPA1 in peripheral nociceptors.

Mechanisms of Transient Receptor Potential Vanilloid 1 Activation and Sensitization by Allyl Isothiocyanate

“…AITC is a natural compound largely responsible for the pungent effect of mustard and wasabi and has been widely used for research purposes to induce experimental irritation and local inflammation (see for example Reeh et al, 1986;McMahon and Abel, 1987;Caterina et al, 2000;García-Martinez et al, 2002;Simons et al, 2004;Carstens and Mitsuyo, 2005;Bautista et al, 2006;Kwan et al, 2006;Albin et al, 2008;Merrill et al, 2008;Sawyer et al, 2009;Dunham et al, 2010). Until recently, these responses were attributed to the nociceptor channel TRPA1 (Bautista et al, …”

Menthol Activation of Corneal Cool Cells Induces TRPM8-Mediated Lacrimation but Not Nociceptive Responses in Rodents

“…A previous study also has demonstrated that a relatively high concentrations of menthol (6.4-64 mM) enhanced coldevoked activity in trigeminal subnucleus caudalis nociceptive neurons with intraoral receptive fields. 62 Similarly, intraoral menthol (19 mM) enhanced lingual cold pain in human subjects, 63 and even higher concentrations of menthol have been used to model cold pain in humans. [64][65][66] The results of studies using these high concentrations of menthol should be interpreted with caution, since such high concentrations produce effects that are not mediated by TRPM8 channels.…”

Inhibition of TRPM8 Channels Reduces Pain in the Cold Pressor Test in Humans

“…One possible explanation is that blocking TRPM8-mediated cold sensation unmasks constitutive activity of other temperature-sensing TRP channels expressed in the mouth, such as TRPV1 and TRPA1 (Zanotto et al, 2007;Gerhold and Bautista, 2009;Morgan et al, 2009). Furthermore, clinical and preclinical studies using agonists for the different channels have clearly demonstrated an interplay between them and an ability to modulate cold and heat sensitivity (Zanotto et al, 2007;Albin et al, 2008). However, although it is possible to agonize the channels to give rise to sensations, there was no exogenous activation in our study (such as hot drinks or food).…”