RESUMEN
The oral sensation elicited by carbonated water is reduced by capsaicin and by blockers of carbonic anhydrase. We have investigated the temporal profile of this sensation and its cross-desensitization by capsaicin. We additionally tested if the sensation is influenced by amiloride. Following pretreatment of half of the dorsal tongue with 33 p.p.m. capsaicin, carbonated water was flowed over the tongue bilaterally for 5, 15 or 60 s. Subjects then performed a two-alternative forced choice test by indicating which side of the tongue had a stronger sensation and separately rated the sensory intensity on each side. Capsaicin significantly reduced the intensity of sensation elicited by carbonated water, consistent with cross-desensitization. This effect was weaker at 60 s because of a significant decline (desensitization) in ratings of the intensity of carbonated water on both sides of the tongue. Pretreatment with amiloride resulted in a small but significant increase in the intensity of the sensation elicited by the 15 s carbonated water stimulus, suggesting an amiloride-sensitive transduction mechanism.
Asunto(s)
Amilorida/farmacología , Capsaicina/farmacología , Bebidas Gaseosas , Gusto/efectos de los fármacos , Administración Oral , Adulto , Diuréticos/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Transducción de Señal , Factores de Tiempo , Lengua/fisiologíaRESUMEN
The irritant properties of menthol and its interactions with nicotine were investigated psychophysically in human subjects. In the first experiment, 0.3% L-menthol was applied successively to one side of the tongue 10 times at a 1-min interval (30-s interstimulus interval, ISI), and subjects rated the intensity of the perceived irritation. The intensity of irritation progressively decreased across trials, consistent with desensitization. To test for cross-desensitization of nicotine-evoked irritation by menthol, nicotine (0.6%) was applied to both sides of the tongue simultaneously, 5 min after the conclusion of menthol application. Using both a two-alternative forced choice (2-AFC) paradigm, and also by obtaining independent ratings of the irritant intensity on each side of the tongue, it was found that nicotine-evoked irritation was significantly weaker on the menthol-pretreated side. To control for a possible confounding effect of cooling, nicotine was applied bilaterally only after the cooling sensation of menthol had subsided. Nicotine-induced irritation was still significantly weaker on the menthol-pretreated side, consistent with cross-desensitization of nicotine-evoked irritation by menthol. In a final experiment, menthol was repeatedly applied to one side of the tongue at a shorter (20 s) interval (5-s ISI), and elicited a rapid increase in irritant sensation over the initial trials, consistent with sensitization, followed in subsequent trials by a progressive reduction in irritation (desensitization). After a 5-min rest period, self-desensitization was confirmed. Repeated application of menthol at the same short ISI was then resumed, and resulted in a significant mean increase in irritant intensity consistent with stimulus-induced recovery (SIR).
Asunto(s)
Desensibilización Psicológica , Irritantes/farmacología , Mentol/farmacología , Nicotina/farmacología , Nociceptores/efectos de los fármacos , Termorreceptores/efectos de los fármacos , Lengua/inervación , Adolescente , Adulto , Interacciones Farmacológicas , Humanos , Persona de Mediana Edad , Psicofísica , Umbral Sensorial/efectos de los fármacos , Nervio Trigémino/efectos de los fármacosRESUMEN
Despite the widespread consumption of products containing chemicals that irritate the oral mucosa, little is known about the underlying neural mechanisms nor is there a corresponding animal model of oral irritation. We have developed a rodent model to assess aversion to capsaicin in drinking water, using a paired preference paradigm. This method was used to test the hypothesis that the neuromodulator substance P (SP) plays a role in the detection of intra-oral capsaicin. 'Knockout' (KO) mice completely lacking SP and neurokinin A due to a disruption of the preprotachykinin A gene and a matched population of wild-type (WT) mice had free access to two drinking bottles, one containing water and the other capsaicin at various concentrations. Both KO and WT mice showed a concentration-dependent aversion to capsaicin. KO mice consumed significantly more capsaicin than WT at a single near threshold (1.65 microM) concentration, indicating that SP plays a limited role in the detection and rejection of oral irritants.
Asunto(s)
Capsaicina/administración & dosificación , Ratones Noqueados/genética , Neuroquinina A/genética , Sustancia P/genética , Umbral Gustativo/fisiología , Administración Oral , Animales , Capsaicina/química , Tolerancia a Medicamentos/fisiología , Irritantes/administración & dosificación , Irritantes/química , Ratones , Ratones Congénicos , Ratones Endogámicos C57BL , Ratones Noqueados/fisiología , Modelos Animales , Neuroquinina A/biosíntesis , Precursores de Proteínas/biosíntesis , Precursores de Proteínas/genética , Especificidad de la Especie , Sustancia P/biosíntesis , Taquicininas/biosíntesis , Taquicininas/genéticaRESUMEN
Psychophysical methods were used to investigate the irritant sensory properties of concentrated NaCl. The first experiment investigated potential sensitization and desensitization properties. Subjects rated the intensity of the irritation elicited by 10 successive applications of 5 M NaCl on one side of the dorsal surface of the tongue. The mean irritant sensation increased significantly across trials, consistent with sensitization. To test for self- and cross-desensitization effects of unilateral sequential stimulation with NaCl followed by a 10-min rest period, either 5 M NaCl or 10 microM capsaicin was applied bilaterally. In a two-alternative forced-choice (2-AFC) test, subjects indicated which side of the tongue had a stronger irritant sensation. They also rated the intensity of irritation on each side separately. When NaCl was applied bilaterally, the side not previously receiving NaCl was chosen as stronger by a significant majority of subjects and was given significantly higher intensity ratings, consistent with self-desensitization. In contrast, when capsaicin was applied bilaterally, the side that had previously received sequential NaCl was perceived as having a significantly more intense irritation, consistent with cross-sensitization. In a second experiment, the effect of amiloride on NaCl-evoked irritation was studied. One side of the tongue was treated with 1 mM amiloride, after which 5 M NaCl was applied bilaterally and subjects performed the same 2-AFC and rating procedures. Since amiloride significantly reduced the intensity of the irritant sensation, the contribution of amiloride-sensitive ionic currents or the Na+/H+ exchange pump (NHE) are suggested as possible transduction mechanisms in lingual nociceptors mediating NaCl-evoked oral irritation.
Asunto(s)
Capsaicina/toxicidad , Irritantes/toxicidad , Boca/efectos de los fármacos , Cloruro de Sodio/toxicidad , Adolescente , Adulto , Amilorida/farmacología , Diuréticos/farmacología , Femenino , Humanos , Canales Iónicos/efectos de los fármacos , Canales Iónicos/metabolismo , MasculinoRESUMEN
In a first experiment, human subjects used a bipolar scale to rate the irritant sensation elicited by 10 sequentially repeated applications of either 3 ppm capsaicin or 250 mM citric acid on one side of the dorsal surface of the tongue, at 1 min intervals (30 s inter-stimulus interval). Citric acid-evoked irritation significantly increased across trials, consistent with sensitization. With capsaicin there was a large degree of inter- and intra-individual variation in successive ratings with no overall sensitization. Following the sequential stimulation series and a 10 min rest period, self- and cross-desensitization effects were tested in a two-alternative forced choice (2-AFC) paradigm by placing either citric acid or capsaicin on both sides of the tongue and asking subjects to indicate which side of the tongue yielded a stronger irritant sensation. Subjects also gave separate intensity ratings for irritation on each side of the tongue. Capsaicin self-desensitization was confirmed, while cross-desensitization to citric acid was not observed. In addition, citric acid self-desensitization and cross-desensitization to capsaicin were observed. In a second experiment a stronger capsaicin solution (33 ppm) was applied to one side of the tongue using cotton swabs. After the burning sensation elicited by capsaicin had disappeared, citric acid was applied bilaterally and cross-desensitization was observed using the same 2-AFC and rating procedures. This was followed by repeated re-application of citric acid at 1 min intervals to the capsaicin-treated side. The irritant sensation elicited by citric acid increased significantly, indicating a 'cross-stimulus-induced recovery' from capsaicin desensitization. In a final experiment we investigated the effect of the sodium channel blocker amiloride on the perceived irritation elicited by citric acid or capsaicin. Following application of amiloride to one side of the tongue with cotton swabs, either citric acid or capsaicin was applied bilaterally and subjects asked to perform a 2-AFC and intensity ratings. Amiloride significantly, albeit weakly, reduced the irritation elicited by citric acid while it weakly but significantly enhanced capsaicin-evoked irritation. These findings are discussed in terms of involvement of vanilloid and acid-sensitive ion channels in acid-evoked irritation and pain.
Asunto(s)
Capsaicina/administración & dosificación , Ácido Cítrico/administración & dosificación , Irritantes/administración & dosificación , Sensación , Adolescente , Adulto , Interacciones Farmacológicas , Tolerancia a Medicamentos , Femenino , Humanos , Masculino , Percepción , Soluciones , Lengua/efectos de los fármacosRESUMEN
Repeated application of capsaicin at a 1-min interstimulus interval (ISI) to the tongue induces a progressively increasing irritant sensation (sensitization), followed after a rest period by reduced sensitivity to further capsaicin (desensitization). Sequential reapplication of capsaicin induces irritation that eventually increases to initial levels: stimulus-induced recovery (SIR). In contrast, repeated application of nicotine elicits a declining irritant sensation across trials. To investigate possible neural correlates of these phenomena, we recorded from single units in superficial laminae of the dorsomedial trigeminal subnucleus caudalis (Vc) that responded to noxious thermal (54 degrees C) and chemical (1 M pentanoic acid) stimulation of the tongue of anesthetized rats. We then recorded responses to either capsaicin (330 microM) or nicotine (0.6 M), delivered either once, repeatedly at 1-min ISI, or continually by constant flow. After the initial capsaicin application and a rest period, the capsaicin was reapplied in the identical manner to test for SIR. The mean response of 14 Vc units to sequential application of pentanoic acid did not vary significantly across trials, indicating lack of tachyphylaxis or sensitization. The averaged response of 11 Vc units to repeated capsaicin increased significantly across the first eight trials and then plateaued. Following the rest period, spontaneous firing had returned to the precapsaicin level. With capsaicin reapplication, the averaged response increased again after a significant delay (due to desensitization), but did not reattain the peak firing rate achieved in the initial series (partial SIR). Constant-flow application of capsaicin induced an identical sensitization followed by nearly complete SIR. A single application of capsaicin induced a significant rise in firing in eight other units, but the rate of rise and maximal firing rate were both much lower compared with repetitive or constant-flow capsaicin. When capsaicin was reapplied once after the rest period, there was no change in firing rate indicating absence of SIR. These results indicate that maintenance of the capsaicin concentration induces a progressive increase in neuronal response that parallels sensitization. With recurrent capsaicin application, desensitization can be overcome to result in a delayed recovery of Vc responses similar to SIR. In contrast, the averaged response of 17 Vc units to repeated or constant-flow application of nicotine increased only over the first 3 min, and then decreased to spontaneous levels even as nicotine was still being applied. These results are consistent with the decrease in the perceived irritation elicited by sequential application of nicotine in humans.
Asunto(s)
Capsaicina/farmacología , Estimulantes Ganglionares/farmacología , Neuronas/efectos de los fármacos , Nicotina/farmacología , Núcleo Espinal del Trigémino/efectos de los fármacos , Administración Oral , Animales , Capsaicina/administración & dosificación , Tolerancia a Medicamentos , Calor , Masculino , Nicotina/administración & dosificación , Ácidos Pentanoicos/farmacología , Ratas , Ratas Sprague-Dawley , Lengua/efectos de los fármacos , Núcleo Espinal del Trigémino/citologíaRESUMEN
We previously showed that sequential application of a relatively low nicotine concentration (7.4 mM) to the tongue, followed by a rest period, induced self-desensitization, i.e. a reduction of oral irritation elicited by subsequent nicotine, but not cross-desensitization of capsaicin-evoked irritation. We presently investigated if cross-desensitization of capsaicin-evoked irritation might be induced by higher concentrations of nicotine. Nicotine (74 or 300 mM) was applied once, unilaterally to the tongue of human subjects. When the irritant sensation had completely subsided, capsaicin (33 microM) was applied bilaterally. In a 2-alternative forced-choice (2-AFC) test, subjects indicated which side of the tongue had a stronger irritant sensation. They additionally rated the intensity of irritation on each side separately. Pretreatment with 74 mM nicotine did not induce cross-desensitization, since no significant difference was observed in intensity ratings or in choice of the treated vs. non-treated side in the 2-AFC. However, 300 mM nicotine did induce cross-desensitization, since a significant majority of subjects chose the non-treated side as having a stronger capsaicin-evoked irritant intensity and assigned significantly higher ratings to that side. These psychophysical findings are discussed in terms of possible neural mechanisms of desensitization.
Asunto(s)
Capsaicina/farmacología , Interacciones Farmacológicas/fisiología , Nicotina/farmacología , Dolor/inducido químicamente , Dolor/tratamiento farmacológico , Lengua/efectos de los fármacos , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nicotina/metabolismo , Nociceptores/efectos de los fármacos , Nociceptores/metabolismo , Dolor/fisiopatología , Lengua/patología , Lengua/fisiopatologíaRESUMEN
To characterize the role of neuronal nicotinic acetylcholine receptors (nAChRs) in oral irritation and pain, we employed the method of c-fos immunohistochemistry to map the locations and numbers of brainstem neurons that express the immediate-early gene, c-fos, after application of nicotine to the tongue, either alone or after pretreatment with cholinergic antagonists. Groups of anesthetized rats received the following chemicals delivered bilaterally to the dorsal tongue: (1) 0.9% NaCl followed by nicotine (1%, 61 mM), (2) the nAChR antagonist, mecamylamine 0.1% (= 4.9 mM) followed by nicotine, (3) the muscarinic antagonist atropine (0.1% 1.46 mM) followed by nicotine, (4) atropine (1%, 14.6 mM) followed by nicotine, (5) 0.9% NaCl as a control, and (6) unstimulated controls. Two hours later, animals were perfused with phosphate-buffered saline followed by 4% paraformaldehyde through the aorta. Post-fixed brainstems were cut in 50-micron frozen sections and immunohistochemically processed for fos-like immunoreactivity (FLI). Following application of nicotine, there were significant increases in FLI compared with saline-treated controls in dorsomedial and ventrolateral aspects of the trigeminal caudalis. Pretreatment with either mecamylamine or the high (1%) concentration of atropine significantly reduced nicotine-evoked FLI in these areas, while pretreatment with the low (0.1%) atropine concentration did not significantly affect FLI. These results are consistent with the idea that nicotine activates nAChRs residing on lingual nociceptive fibers, which, in turn, excite neurons in trigeminal caudalis.
Asunto(s)
Neuronas/fisiología , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Receptores Nicotínicos/fisiología , Núcleo Caudal del Trigémino/fisiología , Administración Oral , Animales , Atropina/farmacología , Masculino , Mecamilamina/farmacología , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/inervación , Mucosa Bucal/fisiología , Antagonistas Muscarínicos/farmacología , Neuronas/química , Neuronas/efectos de los fármacos , Antagonistas Nicotínicos/farmacología , Nociceptores/efectos de los fármacos , Nociceptores/fisiología , Dolor/inducido químicamente , Dolor/fisiopatología , Proteínas Proto-Oncogénicas c-fos/análisis , Ratas , Ratas Sprague-Dawley , Taquifilaxis/fisiología , Lengua/efectos de los fármacos , Lengua/inervación , Lengua/fisiología , Núcleo Caudal del Trigémino/química , Núcleo Caudal del Trigémino/citologíaRESUMEN
The sensation produced by carbonated beverages has been attributed to chemical excitation of nociceptors in the oral cavity via the conversion of CO(2) to carbonic acid in a reaction catalyzed by carbonic anhydrase. In separate studies, we tested if the carbonic anyhdrase blocker, acetazolamide, reduced either the intensity of sensation in humans or c-fos expression by trigeminal neurons in rats, evoked by application of carbonated water to the tongue. In the psychophysical experiment, one-half of the dorsal tongue was pretreated with acetazolamide (1 or 2%), after which the tongue was exposed bilaterally to carbonated water. In a two-alternative forced-choice paradigm, subjects chose which side of the tongue yielded a stronger sensation and additionally rated the magnitude of sensation on each side. Pretreatment with acetazolamide reduced the magnitude of sensation elicited by carbonated water in a concentration-dependent manner, since a significant majority of subjects chose the untreated side of the tongue as having a stronger sensation and assigned significantly higher intensity ratings to that side. Acetazolamide did not affect the irritant sensation from citric acid, while capsaicin pretreatment reduced both the sensation elicited by carbonated water and the irritation induced by citric acid application. In a separate experiment using rats, delivery of carbonated water to the tongue significantly increased the number of cells expressing c-fos-like immunoreactivity in the dorsomedial trigeminal nucleus caudalis (versus saline controls); this was significantly reduced by pretreatment with acetazolamide. Our results support the hypothesis that carbonated water activates lingual nociceptors via conversion of CO(2) to carbonic acid; the nociceptors in turn excite trigeminal neurons involved in signaling oral irritation.
Asunto(s)
Agua/administración & dosificación , Administración Oral , Adolescente , Adulto , Animales , Dióxido de Carbono/química , Femenino , Humanos , Concentración de Iones de Hidrógeno , Inmunohistoquímica , Masculino , Proteínas Proto-Oncogénicas c-fos/metabolismo , Psicofísica , Ratas , Ratas Sprague-Dawley , Lengua/efectos de los fármacos , Lengua/metabolismo , Lengua/fisiología , Agua/químicaRESUMEN
Carbonated drinks elicit a sensation that is highly sought after, yet the underlying neural mechanisms are ill-defined. We hypothesize that CO(2) is converted via carbonic anhydrase into carbonic acid, which excites lingual nociceptors that project to the trigeminal nuclei. We investigated this hypothesis using three methodological approaches. Electrophysiological methods were used to record responses of single units located in superficial laminae of the dorsomedial aspect of trigeminal subnucleus caudalis (Vc) evoked by lingual application of carbonated water in anesthetized rats. After pretreatment of the tongue with the carbonic anhydrase inhibitor dorzolamide, neuronal responses to carbonated water were significantly attenuated, followed by recovery. Using c-Fos immunohistochemistry, we investigated the distribution of brainstem neurons activated by intraoral carbonated water. Fos-like immunoreactivity (FLI) was significantly higher in the superficial laminae of dorsomedial and ventrolateral Vc in animals treated with carbonated water versus controls. Dorzolamide pretreatment significantly reduced FLI in dorsomedial Vc. We also examined the sensation elicited by carbonated water in human psychophysical studies. When one side of the tongue was pretreated with dorzolamide, followed by bilateral application of carbonated water, a significant majority of subjects chose the untreated side as having a stronger sensation and assigned significantly higher intensity ratings to that side. Dorzolamide did not reduce irritation elicited by pentanoic acid. The present data support the hypothesis that carbonated water excites lingual nociceptors via a carbonic anhydrase-dependent process, in turn exciting neurons in Vc that are presumably involved in signaling oral irritant sensations.
Asunto(s)
Tronco Encefálico/fisiología , Bebidas Gaseosas , Inhibidores de Anhidrasa Carbónica/farmacología , Neuronas/fisiología , Sensación/fisiología , Sulfonamidas/farmacología , Tiofenos/farmacología , Lengua/inervación , Núcleos del Trigémino/fisiología , Potenciales de Acción/efectos de los fármacos , Adulto , Animales , Electrofisiología/métodos , Femenino , Lateralidad Funcional , Humanos , Masculino , Proteínas Proto-Oncogénicas c-fos/análisis , Proteínas Proto-Oncogénicas c-fos/genética , Ratas , Ratas Sprague-DawleyRESUMEN
Using a bipolar rating scale, human subjects rated the intensity of irritation sensation evoked by repeated application of piperine (75 p.p.m.) or nicotine (0.12%) to one side of the dorsal surface of the tongue. The intensity of irritation elicited by repeated application of piperine significantly increased, while irritation elicited by repeated nicotine significantly decreased. We additionally tested if nicotine or piperine desensitized the tongue. After either piperine or nicotine was repeatedly applied to one side of the tongue, a 5 or 10 min rest period ensued, followed by re-application of piperine or nicotine to both sides of the tongue. Subjects were asked to choose which side of the tongue gave rise to a stronger irritation in a two-alternative forced choice (2-AFC) paradigm. In addition, they gave separate ratings of the intensity of irritation on the two sides of the tongue. When piperine was applied bilaterally after unilateral pretreatment with piperine and a 10 min rest period, subjects consistently chose the non-pretreated side to yield stronger irritation and assigned significantly higher ratings to that side, indicative of piperine self-desensitization. A similar self-desensitization effect was found when bilateral application of nicotine followed unilateral treatment with nicotine and a 5 min rest period. Unilateral treatment with piperine also reduced nicotine-evoked irritation on the pretreated side (cross-desensitization), but treatment with nicotine did not affect piperine-evoked irritation. This asymmetrical cross-desensitization pattern is similar to that observed between capsaicin and nicotine and constitutes an additional similarity between piperine and capsaicin.
Asunto(s)
Alcaloides , Irritantes/farmacología , Nicotina/farmacología , Piperidinas/farmacología , Psicofísica , Lengua/efectos de los fármacos , Adulto , Benzodioxoles , Femenino , Humanos , Masculino , Alcamidas Poliinsaturadas , Lengua/fisiologíaRESUMEN
Using a two-alternative forced-choice (2-AFC) discrimination test coupled with category intensity ratings, we investigated the effect of mecamylamine, an antagonist of neuronal nicotinic acetylcholine receptors (nAchRs), on oral irritation elicited by nicotine or capsaicin. Mecamylamine (0.075%) was first delivered to one side of the tongue with distilled H2O delivered to the other side. After 10 min either capsaicin (1 ppm) or nicotine (0.12%) was applied bilaterally to the tongue, and subjects were asked to choose which side yielded a stronger sensation (2-AFC) as well as to provide a rating of the irritation intensity difference between the two sides of the tongue. When nicotine was given after mecamylamine, a significant proportion of subjects chose the mecamylamine-untreated side as yielding stronger irritation. When capsaicin was given after mecamylamine, both sides of the tongue were chosen in equal numbers. These data indicate that mecamylamine reduced irritation elicited by nicotine but not capsaicin, and provide further evidence that nicotine oral irritation is mediated via a neuronal nAchR while capsaicin activates trigeminal fibers via a separate molecular receptor.
Asunto(s)
Capsaicina/antagonistas & inhibidores , Irritantes/antagonistas & inhibidores , Mecamilamina/farmacología , Nicotina/antagonistas & inhibidores , Receptores de Droga/metabolismo , Lengua/efectos de los fármacos , Adulto , Capsaicina/metabolismo , Discriminación en Psicología/efectos de los fármacos , Femenino , Humanos , Masculino , Nicotina/metabolismo , Receptores de Droga/efectos de los fármacos , Receptores Nicotínicos/efectos de los fármacosRESUMEN
When delivered to the oral mucosa, a variety of naturally occurring chemicals such as capsaicin from red chili peppers, piperine from black pepper, and nicotine from tobacco, cause a diffuse burning sensation often referred to as irritation. The burning sensation evoked by capsaicin increases when delivered repeatedly at 1 min intervals (sensitization), but then decreases markedly following a 10 min rest period (self-desensitization). It is also interesting that following desensitization by capsaicin, irritant sensations evoked by other chemicals are also reduced (cross-desensitization), suggesting that oral irritation from some agents may be mediated by a population of capsaicin-sensitive trigeminal polymodal nociceptors. Although nicotine is a major component in tobacco smoke, little is known about its sensory properties. Accordingly, a study of the oral irritant effects of nicotine as compared with capsaicin was initiated. Whereas capsaicin (0.5 or 3 ppm; repeated at 1 min intervals over 10 min) evoked significantly stronger sensations (sensitization), there was a significant decrement in sensations to repeated application of nicotine (0.1%). After the subjects had received either repeated capsaicin or nicotine on one side of the tongue, a rest period ensued followed by a bilateral application of either capsaicin or nicotine. Subjects were, then, asked to choose which side yielded a stronger sensation (two-alternative forced choice). Following capsaicin pretreatment, all subjects reported that capsaicin evoked a stronger sensation on the previously untreated side (capsaicin self-desensitization). Similar self-desensitization was observed with nicotine. Furthermore, nicotine was reported to evoke a significantly weaker sensation on the side of the tongue pretreated with capsaicin (cross-desensitization). In contrast, equal numbers of subjects reported capsaicin to evoke a stronger sensation on either the nicotine-pretreated side or the untreated side, indicating an absence of cross-desensitization. These results are discussed in terms of physiological mechanisms that might underlie the contrasting sensory effects of nicotine versus capsaicin.
Asunto(s)
Capsaicina/farmacología , Estimulantes Ganglionares/farmacología , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/fisiología , Nicotina/farmacología , Gusto , HumanosRESUMEN
Psychophysical methods were used to assess changes in the intensity of irritant sensations elicited by repeated application of capsaicin and nicotine delivered unilaterally to the tongue of human subjects. Whereas capsaicin (0.5 or 3 p.p.m.; repeated at 1 min intervals over 10 min) evoked progressively stronger ratings of irritation (sensitization), there was a significant decrement in irritation ratings (desensitization) to repeated application of nicotine (0.1%). A two-alternative forced-choice (2-AFC) procedure was additionally used to test for self- and cross-desensitization. After the subjects had received either repeated capsaicin or nicotine, a rest period ensued followed by the 2-AFC procedure. Either capsaicin or nicotine was delivered bilaterally to the tongue and subjects were asked to choose which side yielded a stronger sensation. Following capsaicin pretreatment, subjects reported that capsaicin evoked a stronger sensation on the previously untreated side (capsaicin self-desensitization). Similar self-desensitization was observed with nicotine. Furthermore, nicotine evoked a significantly weaker sensation on the side of the tongue pretreated with capsaicin (cross-desensitization). In contrast, capsaicin did not consistently evoke a weaker sensation on the nicotine-pretreated side, indicating an absence of cross-desensitization. These results are discussed in terms of physiological mechanisms that might underlie the contrasting sensory effects of nicotine versus capsaicin.