ABSTRACT
Sensory modalities are important for survival but the molecular mechanisms remain challenging due to the polymodal functionality of sensory neurons. Here, we report the C. elegans outer labial lateral (OLL) sensilla sensory neurons respond to touch and cold. Mechanosensation of OLL neurons resulted in cell-autonomous mechanically-evoked Ca
ABSTRACT
PURPOSE: Bladder outlet obstruction (BOO) causes storage and voiding dysfunction in the lower urinary tract. We investigated the expression of transient receptor potential cation channel subfamily M member 8 (TRPM8) to evaluate the relationship between TRPM8 expression and overactive bladder (OAB) in a rat model of BOO. METHODS: Fifty female Sprague-Dawley rats were divided into 4 groups; normal (n=10), normal-menthol (n=10), BOO (n=15), BOO-menthol (n=15). After 3 weeks, cystometry was performed by infusing physiological saline and menthol (3 mM) into the bladder at a slow infusion rate. The histological changes and expression of TRPM8 in the bladder were investigated by Masson's trichrome staining, immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS: Cystometry showed that the intercontraction interval (ICI; 428.2+/-23.4 vs. 880.4+/-51.2, P<0.001), micturition pressure (MP; 25.7+/-1.01 vs. 71.80+/-3.01, P<0.001), and threshold pressure (2.9+/-0.25 vs. 9.2+/-1.58, P<0.01) were significantly increased in BOO rats. The bladder wall was significantly dilated compared with the control. Detrusor muscle hypertrophy and a thick mucosa layer were observed in BOO bladder. After menthol treatment, ICIs were decreased and MPs were increased in the menthol treatment groups. TRPM8-positive cells and mRNA were predominantly increased in the bladder and dorsal root ganglia of all groups compared with the normal group. CONCLUSIONS: Increased bladder wall thickness and proportion of collagen probably affect voiding dysfunction. Furthermore, an increase of TRPM8 expression in BOO may induce entry of Ca2+ from the extracellular space or stores. The increase of Ca2+ probably causes contraction of smooth muscle in BOO. However, OAB symptoms were not observed after menthol treatment although the expression of TRPM8 was abundant in the bladder epithelium after menthol treatment. Although OAB in BOO models may be caused by complex pathways, regulation of TRPM8 presents possibilities for OAB treatment.
Subject(s)
Animals , Female , Humans , Rats , Cold Temperature , Collagen , Contracts , Epithelium , Extracellular Space , Fluorescent Antibody Technique , Ganglia, Spinal , Hypertrophy , Menthol , Mucous Membrane , Muscle, Smooth , Muscles , Rats, Sprague-Dawley , RNA, Messenger , Urinary Bladder , Urinary Bladder Neck Obstruction , Urinary Bladder, Overactive , Urinary Tract , UrinationABSTRACT
The present study examined the recruitment threshold of motor units (MUs) and the cold reflex activation of the cutaneous receptors at the first turning point (TP1) and the second turning point (TP2) of decreasing skin temperature. The skin temperatures of the biceps brachii were continuously reduced using a cooling chamber fixed at -10°C. TP1 and TP2 appeared at 25.5±0.5°C and 18.5±2.21°C, respectively. The data were collected at±1°C of TP1 and TP2 (TP1-B, TP1-A, TP2-B and TP2-A) . The MUs was collected during a slow ramp contraction for 3 sec to 20% maximal voluntary contraction (20%MVC) at the each measure points (TE) . The rates of decrease in skin temperature were 1.242±0.349°C min at slope-1 (TP1-B), 0.627±0.284°C rain at slope-2 (TP1-A and TP2-B), and 0.201±0.045°C/min at slope-3 (TP2-A) . The difference of the threshold force value (ΔTF= TE-control value) of LT-MUs were positive value, on the other hand, ΔF of HT-MUs were negative value at TP1-B, TP1-A, TP2-B and TP2-A. The changes of ΔTF of LT-MUs were a little at TP1-B, TP1-A, TP2-B, and increased markedly more at TP2-A than at TP1-B (p<0.05) . On the other hand, the ΔTF of HT-MUs decreased significantly more at TP1-B than at TP1-A and TP2-B (p<0.05), however, it did not significantly differ at TP2-A. These results suggested that the threshold force of HT-MUs depend on skin temperature and LT-MUs depend on decrease speed of skin temperature.