NT4/5 mutant mice have deficiency in gustatory papillae and taste bud formation. (33/1447)

Neurotrophins are key determinants for controlling the survival of peripheral neurons during development. Brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT4/5) exert their action through a common trkB receptor but independently support gustatory sensory neurons. To assess the role of NT4/5 during development, we examined the postnatal development and maintenance of fungiform taste buds in mice carrying a deletion of NT4/5. The absence of NT4/5 results in embryonic deficits in gustatory innervation and a reduced number of fungiform papillae at birth. No degenerative deficits of fungiform papillae were observed for the first 3 weeks of postnatal development. However, these remaining fungiform papillae were smaller in appearance and many did not contain taste pores. By postnatal day 60, there was 63% decrease in the number of fungiform papillae, and remaining papillae were smaller in size or modified into filiform-like spines. These papillae had either no taste bud or a taste bud with a reduced number of taste cells compared to controls. These findings demonstrate that the NT4/5 gene functions in the maintenance of fungiform gustatory papillae and raises the possibility for an earlier role in development.  (+info)

Neurobiological and psychophysical mechanisms underlying the oral sensation produced by carbonated water. (34/1447)

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.  (+info)

Oral irritant properties of piperine and nicotine: psychophysical evidence for asymmetrical desensitization effects. (35/1447)

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.  (+info)

Biomechanical basis for lingual muscular deformation during swallowing. (36/1447)

Our goal was to quantify intramural mechanics in the tongue through an assessment of local strain during the physiological phases of swallowing. Subjects were imaged with an ultrafast gradient echo magnetic resonance imaging (MRI) pulse sequence after the application of supersaturated magnetized bands in the x and y directions. Local strain was defined through deformation of discrete triangular elements defined by these bands and was depicted graphically either as color-coded two-dimensional strain maps or as three-dimensional octahedra whose axes correspond to the principal strains for each element. During early accommodation, the anterior tongue showed positive strain (expansive) in the anterior-posterior direction (x), whereas the middle tongue showed negative strain (contractile) in the superior-inferior direction (y). During late accommodation, the anterior tongue displayed increased positive x-direction and y-direction strain, whereas the posterior tongue displayed increased negative y-direction strain. These findings were consistent with contraction of the anterior-located intrinsic muscles and the posterior-located genioglossus and hyoglossus muscles. During propulsion, posterior displacement of the tongue was principally associated with positive strain directed in the x and y directions. These findings were consistent with posterior passive stretch in the midline due to contraction of the laterally inserted styloglossus muscle, as well as contraction of the posterior located transversus muscle. We conclude that MRI of lingual deformation during swallowing resolves the synergistic contractions of the intrinsic and extrinsic muscle groups.  (+info)

Congenital insensitivity to pain with anhidrosis: a case report. (37/1447)

Congenital insensitivity to pain with anhidrosis (CIPA) is a very rare genetic disorder of the peripheral nervous system characterized by recurrent episodes of unexplained fever, generalized anhidrosis, insensitivity to pain and temperature, and accompanied by self-mutilating behavior and mental retardation. We report on a 16 month-old boy with CIPA who exhibited these characteristic clinical features. A sural nerve biopsy revealed markedly reduced numbers of unmyelinated and small myelinated fibers, consistent with the characteristic features of CIPA.  (+info)

Tongue protrusion force and fatiguability in male and female subjects. (38/1447)

Limb and respiratory muscle (diaphragm) strength and fatiguability have been extensively studied in man and are known to vary with age and sex. However, in contrast to limb muscles and the diaphragm, force and fatiguability characteristics have not been studied in upper airway muscles. This study examines the hypotheses that tongue protrusion strength or fatiguability, determined by the properties of the intrinsic muscles and genioglossus, may change with age and may be reduced in males compared to females. A force transducer was used to compare maximal tongue protrusion force (Fmax) and fatiguability in 81 males and 86 females matched for age (mean+/-SD, 43+/-19 yrs, 42+/-19 yrs, respectively). Fatiguability indices were based on the time that subjects could maintain 50% of Fmax. Fmax declined with age in both males (r=-0.57, p<0.001) and females (r=-0.56, p<0.001). Fmax in males was greater than in females (males 26+/-8 N; females 20+/-7 N; p<0.001). However, after correction of Fmax for sex differences in total body muscle (fat-free mass) there was no significant difference between males and females (p=0.3). There was also no difference in fatiguability between males and females (p=0.5). In conclusion, tongue protrusion strength is greater in males compared to females, and decreases with age. If these differences also apply to patients with sleep apnoea, the reduction in maximal tongue protrusion force with age could be of relevance to the observed increase in prevalence and severity of sleep apnoea-hypopnoea syndrome in middle age, but would not explain the gender difference in prevalence.  (+info)

Adult craniocervical and pharyngeal changes--a longitudinal cephalometric study between 22 and 42 years of age. Part II: Morphological uvulo-glossopharyngeal changes. (39/1447)

The purpose of this study was to investigate, by cephalometric means, longitudinal alterations in uvulo-glossopharyngeal morphology in adult males and females, at three different ages with 10-year intervals, and to compare the changes between the two genders. The material consisted of three series of cephalograms of 26 males and 24 females, with approximately a 10-year interval between each series. Alterations with age in males and females included: 1 An increase in the length, thickness, and sagittal area of the soft palate, with a more upright position for both genders. 2 A more upright tongue position and caudally-extended tongue mass for both sexes was found, and the sagittal area of the tongue was significantly increased only in males. 3 There was a decrease in the sagittal dimension of the oropharynx, and at the minimal distance between the base of the tongue and the posterior pharyngeal wall in both males and females. The overall significant inter-sex differences, over a 20-year period, were that males showed a more upright tongue position and more caudally-extended tongue mass, a greater reduction in sagittal dimension of the minimal pharyngeal airway space, a greater increase in the sagittal area of the soft palate, and an increase in the tongue area.  (+info)

Involvement of CYP3A-derived arachidonic acid metabolite(s) in responses to endothelium-derived K+ channel opening substance in monkey lingual artery. (40/1447)

1. In monkey lingual artery strips partially contracted with prostaglandin F2alpha, acetylcholine-induced, concentration-related relaxations were abolished by removal of the endothelium. The response was not significantly influenced by indomethacin but attenuated by NG-nitro-L-arginine (L-NOARG); the effect of the nitric oxide (NO) synthase inhibitor was reversed by L-arginine. 2. The response to acetylcholine resistant to L-NOARG was suppressed in the strips exposed to high K+ media. Charybdotoxin partially inhibited the relaxation, and the remaining relaxation was abolished by additional treatment with apamin, whereas glibenclamide, iberiotoxin or apamin alone was without effect. Relaxations induced by sodium nitroprusside were not influenced by charybdotoxin. 3. The L-NOARG-resistant acetylcholine-induced relaxation was inhibited by metyrapone, proadifen and 17-octadecynoic acid, non-selective cytochrome P450 mono-oxygenase (CYP) inhibitors, and progesterone and ketoconazole, inhibitors selective to CYP3A. The inhibitors did not affect the nitroprusside-induced relaxation. Selective inhibitors of other CYP isoforms, such as debrisoquine and lauric acid, did not reduce the response to acetylcholine. 4. Reaction mixture containing human liver microsome rich in CYPs, arachidonic acid and NADPH incubated at 37 degrees C and filtrated relaxed endothelium-denuded monkey lingual artery strips, used as bioassay tissues. This response was abolished in the strips exposed to high K+ media. The response was also suppressed by combined treatment of the assay tissue with charybdotoxin plus apamin, but was not affected by treatment with iberiotoxin. The reaction mixture co-incubated with ketoconazole failed to relax the strips. 5. It is concluded that the monkey lingual arterial relaxation dependent on the endothelium is mediated by NO and also by a charybdotoxin plus apamin-sensitive but iberiotoxin-insensitive Ca2+-activated K+ channel opening substance(s) that may be a CYP3A-derived arachidonic acid metabolite(s).  (+info)