24 patients in 3 groups (1) Sjögren´s syndrome, N = 9 (2) Undergone head and neck radiation therapy, N = 13 (3) Xerostomia being either drug-induced or unknown etiology, N = 3
Electrodes placed on the dorsum of the tongue and pressed against the hard palate; the maximum voltage was 6 V with a current of 9 uA; the maximum power was 12.4 mJ in a 3 minute stimulus cycle; the stimulus was increased until the patients reached their level of tolerance.
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Subjective patient evaluation was performed Intraoral clinical examination was performed.
This noninvasive electrostimulation has shown to be effective in patients with xerostomia due to Sjögren’s syndrome or radiation therapy; patients reported slight to substantial improvement.
Electrodes placed on the dorsum of the tongue and pressed against the hard palate. An intensity control knob with intervals from 0 to 10 set peak stimulus output between 0 and 6 V; the maximum average current output is 9 uA and corresponds to a maximum average power dissipation of 0.2 uW.
Placebo device and electrodes
Subjective patient evaluation was performed. Intraoral clinical examination was performed The whole saliva flow rates were measured.
The mean poststimulation whole saliva flow rate of subjects using the active device increased, while the mean poststimulation rate of those using a placebo device did not (). The results in this study indicate that some Sjögren’s syndrome patients with residual salivary flow show a significant response to electrical stimulation, but others with low or absent whole saliva flow rates do not respond.
Electrodes placed on the dorsum of the tongue and pressed against the hard palate. The unit stimulus switch was pressed, and the stimulus intensity was adjusted to settings of 1–10 with the objective of reaching a setting of 10. The stimulation automatically shut off after 3 min.
Placebo device and electrodes
The whole saliva flow rates were measured. The weight of the saliva was measured.
The patients using active devices showed a statistically greater ( to 0.02) increase in the production of saliva compared to control. At week 1, the differences between the prestimulation and poststimulation salivary production was 80% greater in the group with the active device than in the control group; the differences were 151% at week 2 and 116% at week 4.
Classical acupuncture and superficial acupuncture as placebo
Both groups showed significantly increased salivary flow rates after the acupuncture treatment. In the experimental group 68% and in the control group 50% of the patients had increased salivary flow rates at the end of the observation period. Observation period of 1 year.
Manual acupuncture and acupuncture with low-frequency electrical stimulation (2 Hz) were used.
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Immunoreactivity of neuropeptides was analyzed in the saliva collected 20 minutes before the start of acupuncture stimulation, then for 20 minutes while the needles were in situ, and the for another 20 minutes after the needles were removed.
The results showed significant increases in the release of CGRP, NPY, and VIP both during and after acupuncture stimulation, especially in connection with electro-acupuncture.
Sjogren’s syndrome, irradiation, and other causes, N = 70
Acupuncture and two-way ANOVA were used.
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Salivary flow rates (SFR) for whole unstimulated and stimulated saliva were used as indicators of effects. Data were analyzed 6 month following a baseline course of 24 acupuncture treatments using two-way ANOVA.
Statistically significant differences in unstimulated and stimulated salivary flow rates () in all etiological groups after 24 acupuncture treatments and up to 6 months follow-up compared with baseline.
Codetron treatment was given twice weekly for 6 weeks. Nonpolarizing, balanced biphasic, square electrical pulses of 250 ms duration were delivered in trains with a repetition rate of 4 hz. Each acupuncture point was randomly stimulated for 10 s each time; each session of codetron treatment lasted for a total of 20 min; this was followed by a 2-week break and then another 6-week course of treatment was repeated.
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The whole saliva flow rates were measured. The quality of life questionnaire assessments were performed.
Improvement in xerostomia symptoms was noted, with a mean increase in the visual analog scale score of 86 () and 77 () at 3 and 6 months after treatment completion, respectively. For all patients, the increase in the mean basal and citric acid-primed whole saliva production at 3 and 6 months after treatment completion was also statistically significant ( and , respectively). No statistically significant change in the quality-of-life evaluation compared with baseline was observed.
The TENS electrode pads were placed externally on the skin overlying parotid glands. The pulse rate was fixed at 50 Hz, the pulse duration 250 μsec, and the unit was in normal mode.
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Unstimulated saliva was collected for 5 minutes via the carlson-crittenden cup placed over Stensen’s duct bilaterally, into preweighted vials. The TENS unit was then activated, and stimulated saliva collected for an additional 5 minutes.
15 of 22 subjects demonstrated increased parotid salivary flow when stimulated via the TENS unit. Five experienced no increase and 2 experienced a decrease. The mean unstimulated salivary flow rates were 0.02418 mL/min and mean stimulated salivary flow rate was 0.04946 mL/min; the TENS unit was effective in increasing parotid gland salivary flow in two-third of healthy adult subjects.
Electrostimulation device named GenNarino; delivered during 10 min to the oral mucosa, in the mandibular third molar region (close to the area where the lingual nerve travels alongside the lingual alveolar plate).
Sham (inactive stimulation)
The digital signal of the wetness sensor expressed in numbers was used as a measure of dryness.
After 3 min of the 5 min experiments, significantly lower dryness was seen in the active modes compared with sham. No significant side effects were observed.
Acupuncture was conducted twice weekly for 6 weeks in a single-blind setting.
Randomized into two groups: Real or sham acupuncture
The effect was evaluated by measuring whole salivary flow rates and questionnaire-based assessment of subjective symptoms pretreatment and posttreatment (3 and 6 weeks after acupuncture treatment).
Both groups showed a slight increase in whole salivary flow rates, with no significant differences between them. Real acupuncture markedly increased unstimulated salivary flow rates, and improved the score for dry mouth according to the xerostomia questionnaire, by 2.33 points versus 0.33 in the controls.
A Saliwell Crown was placed in the lower third molar area, in vicinity to the lingual nerve. The stimulating device is mounted on a commercially available dental implant. The Saliwell Crown is composed of an electric circuit, two 1.5 V batteries, a microprocessor, a wetness sensor, an IR receiver, and stimulating electrodes.
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Both stimulated and unstimulated saliva flow rates were measured. Subjective patient evaluation was performed.
The results showed a constant significant increase in the salivary secretion and symptomatic improvement as presented in the questionnaires. The frequency of dry and burning mouth has decreased during the study.
20 one-hour sessions with TENS unit; electrode pads placed externally on the skin overlying the parotid glands bilaterally; stimulation was initiated using 4 to 30 mA at 80–100 impulses. The settings ranged from 55 to 80 mA (maximum setting). The duration of treatment was 60 minutes per session. Patients received three E-stimulation treatments per week for a total of one to two months.
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The whole saliva flow rates were measured. Dysphagia and xerostomia index questionnaire was used.
All five patients noticed a significant improvement ( value: 0.002) in dysphagia and a definite increase in saliva production. No untoward side effects/complications were noted in the patients during or after completion of treatment.
ALTENS treatments were administrated with a codetron transcutaneous electrical nerve stimulation (TENS) unit and karaya electrode pads. The locations of the acupuncture points used large intestine 4 (LI4), spleen 6 (SP6), stomach 36 (ST36), and conception vessel 24 (CV24). Square pulses of 250-msec duration were delivered in trains with a 4 hz repetition rate. One acupuncture point was stimulated for 10 seconds at a time. Random switching among electrodes was used. All patients received twice weekly ALTENS sessions (with 20 minutes of stimulation per session) for a total of 24 sessions given in 12 weeks. A maximum of 2 weeks without treatment was allowed, and all outstanding sessions were administrated.
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Preliminary efficacy of ALTENS treatment was assessed using the patient-reported University of Michigan Xerostomia-Related Quality-of-Life-Scale (XeQOLS). The test was administrated at baseline and 6 months after study enrollment.
47 patients were evaluable. 44 of these 47 patients (94%) were successful in complying with ALTENS treatments. Of these, 34 patients (72%) completed all treatment sessions. Six-month XeQOLS were available for 35 patients and indicated that 30 patients (86%) achieved a positive treatment response with a mean ± standard deviation reduction of 35)±36,1%. There were no significant acute side effects associated with ALTENS treatment.
The results indicated that ALTENS treatment for radiation-induced xerostomia can be delivered uniformly in a cooperative, multicenter setting and procedures with possible beneficial treatment response.
The electrodes directly contact the oral mucosa in the mandibular third molar area, in proximity to the lingual nerve.
Sham (inactive stimulation)
Subjective patient evaluation was performed. Intraoral clinical examination was performed. The whole saliva flow rates were measured.
The active device performed better than the sham device for patient-reported xerostomia severity (), xerostomia frequency (), quality of life impairment (), and swallowing difficulty (). At the end of stage 2, statistically significant improvements were verified for patient-reported xerostomia severity (), xerostomia frequency (), oral discomfort (), speech difficulty (), sleeping difficulty (), and resting salivary flow rate ().
GenNarino containing an electronic circuit with a microprocessor, a pair of stimulating electrodes, and a 30 mA/h battery. The electrodes contact the oral mucosa in the mandibular third molar area, close to the lingual nerve. The electrical current is of low intensity and not felt by the patient.
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Subjective patient evaluation was performed. Intraoral clinical examination was performed. The whole saliva flow rates were measured.
Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for the primary outcome, xerostomia severity, and the second outcomes resting whole saliva flow rate, xerostomia frequency, oral discomfort and difficulties in speech, swallowing and sleeping. No significant side effects were detected.
Undergone head and neck radiation therapy, N = 145
Randomized crossover design with participants receiving two group sessions of oral care education and eight acupunctures using standardized methods. Patient-reported outcome measures were completed at baseline and weeks 5, 9, 13, 17, and 21.
Acupuncture group and oral care education group
The whole saliva flow rates were measured.
Acupuncture compared with oral care, produced significant reductions in patients’ reports of severe dry mouth with sticky saliva, needing to sip fluids to swallow food and in waking up at night to drink. No significant changes in either stimulated or unstimulated saliva measurements over time.
Transcutaneous electric nerve stimulation (TENS) placement of pads was approximated bilaterally over the parotid glands. The working parameters of TENS unit were fixed at 50 Hz and 250 µs pulse rate, and the unit was in normal mode.
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The whole saliva flow rates were measured.
Subjects belonging to group B were showing a statistically significant increase in the duration of stimulated parotid salivary flow following the use of TENS.
The study was carried out in three different age groups
a) Individuals from 21 to 35 years
b) 36–50 years
c) Above 51 years
In each group, 30 subjects were taken of whom 15 were males and 15 were females
The transcutaneous electrical nerve stimulation (TENS) electrode pads were placed externally on the skin overlying the parotid glands using an extra-oral device, 1 cm in front of the tragus of the ear, over the parotid region with the TENS unit in the off position. The TENS machine used for the study was MEDIHIGHTEC 8000 combo (MEDIHIGHTEC medical company. Ltd., Taiwan). The pulse rate was fixed at 50 Hz, the pulse duration was fixed at 250 μm, the time was fixed for 5 min, and the unit was used in normal mode.
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Both stimulated and unstimulated saliva flow rates were measured.
29 of 30 patients showed increased saliva flow during stimulation. A statistically significant improvement in saliva production () during stimulation was noted. Extra-oral application of TENS is effective in increasing the whole salivary flow in most of the postradiated oral cancer patients with xerostomia. TENS therapy may be useful as an effective supportive treatment modality in postradiated oral cancer patients.
Oral chronic graft-versus-host disease (cGVHD), N = 6
The electrodes directly contact the oral mucosa in the mandibular third molar area, in proximity to the lingual nerve.
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Clinical examination was performed. Both stimulated and unstimulated saliva flow rates were measured.
Two patients developed mild mucosal lesions in areas in contact with the GenNarino. However, only one of them had a change in the national institutes of health (NIH) score for oral cGVHD. The unstimulated and stimulated salivary flow increased in 4 out of the 5 patients included in the analysis.
The TENS unit was anlaya MedIns – AMS-902. The surface electrode pads were placed externally on the skin, overlying the parotid glands. The unit was preset at a frequency of 100 Hz and a pulse width of 100–150 μs between the measurement of unstimulated and stimulated saliva. Then, the TENS unit was activated and the amplitude was gradually increased to a maximum tolerable level for patients.
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Both stimulated and unstimulated saliva flow rates were measured.
The mean unstimulated flow rate was 1.25 ml/min, the mean stimulated salivary flow rate was 1,41 ml/min. 65 of 80 subjects demonstrate an increase in salivary flow rate on application of TENS. 12 subjects showed no increase in the salivation, while three subjects showed a decrease in the salivary flow. These findings showed an approximately 13% (0.16 ml/min) increase in the mean salivary flow rate on application of TENS.
TENS model-NS electro pulse that generates current through AC at a continuous frequency of 500 Hz with a sweep of 0.5–2 Hz. The electrodes are placed externally on the skin overlying the parotid glands.
Healthy subjects, N = 10
Both stimulated and unstimulated saliva flow rates were measured.
The data analysis revealed that control and S1B group showed increased salivary flow rate after stimulation by TENS therapy, compared with the unstimulated salivary flow, whereas in S1A and S1B group it was found to be statistically nonsignificant.
Undergone head and neck radiation therapy, N = 148
ALTENS were administrated with a codetron TENS unit and karaya electrode pads. Bilateral acupuncture points – SP6, ST36, LI4 – using uncommon electrodes and CV24 using the common electrode were stimulated. Sequences of 250 millisecond square pulses with a 4 Hz repetition rate were delivered. Each acupuncture point, except CV24, was stimulated for 10 seconds at a time; CV24, the site for the common electrode, was stimulated throughout the treatment session. Stimulation intensity was adjusted to produce a deep strong aching sensation at each acupuncture point. All patients were to receive 24 ALTENS sessions (20 minutes each, 2 sessions per week), for 12 weeks.
Randomized study that compared ALTENS with prilocarpine (PC) for relieving radiation-induced xerostomia. Patients: (73 in the pilocarpine group and 75 in the ALTENS group)
The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric-acid-primed whole salivary production (WSP), ratios of positive responders (defined as patients with 20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the common terminology criteria for adverse events version 3. An intention-to-treat analysis was conducted.
Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were 0.53 and 0.27 (PZ.45) and 0.6 and 0.47 (PZ.21). The corresponding percentages of positive responders were 81% and 72% (PZ.34) and 83% and 63% (PZ.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group.
Pilocarpine treatment started within 14 days of enrollment. Patient received 5 mg pilocarpine orally 3 times daily for 12 weeks and then stopped for the rest of the study.
Three groups: 20 young adults, 19 older adults, and 21 patients with dry mouth, N = 60
Used IFCS with a beat frequency of 50 Hz and a carrier frequency of 2000 Hz. The signal type was bipolar. Two independent pairs of electrodes were placed at bilateral submandibular regions symmetrically, targeting both the submandibular and sublingual glands.
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Secreted saliva was collected by using salivette cotton rolls for 15 minutes, either with or without interferential current stimulation (IFCS). Patients were randomly chosen to receive IFCS. Each subject rated pain and discomfort on the visual analog scale (VAS) after each experiment. Saliva chromograin A levels were measured as a stress marker. To compare data between conditions with or without IFCS, a two-sample Student’s t-test analysis was performed.
Saliva flow was slightly increased in those in the dry mouth group receiving IFCS compared with those who did not receive IFCS (approximately 130%). However, no such difference was found in the young and older adult groups. There was no significant difference in the VAS values of pain and discomfort or in the stress marker levels between patient who received or did not receive IFCS in the three groups. IFCS delivered to submandibular and sublingual glands may promote saliva secretion in persons who suffer from dry mouth in a manner that does not induce pain or physical stress.
50 postmenopausal females with or without dryness Divided into 2 groups of 25 each; (1) postmenopausal women with oral dryness and (2) postmenopausal women without oral dryness
The TENS unit was ultrasonic TENS. The technical specifications of the TENS unit were 220 V, A/C 50 Hz, 0–100 mA at 1 k load, biphasic wave form, available in pulsed/continuous form, and 2 intensities, I and II. The electrode of TENS unit was then placed vertically, externally on the skin overlying the parotid gland, in the preauricular area bilaterally, 1 cm in front of the tragus area.
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Unstimulated whole saliva was collected by the low forced splitting method. External salivary secretion of parotid glands by electrodes of TENS unit was done and sialometry was repeated. The salivary flow rates were compared within both groups before and after stimulation and between two groups.
The mean salivary flow rates at baseline were statistically significantly lower in group 1 than group 2. There was a mean increase of 0.33 ml and 0.46 ml with TENS stimulation in the two groups, respectively. Postmenopausal women with perception of oral dryness had lower salivary flow rates. 90% of the subjects, irrespective of oral dryness status, responded to TENS therapy. TENS stimulation resulted in a statistically significant increase in the quantity of whole saliva flow rate in postmenopausal women with or without dryness.
TENS units were placed over the parotid region. The intensity control switch was adjusted for patient’s comfort. The intensity was turned up 1 increment at a time at 5 s intervals until the optimal intensity level was reached.
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Unstimulated saliva was collected using modified carlson crittenden cup placed over the Stenson’s duct bilaterally for 5 min and measured. A paired t-test, evaluating mean changes in stimulated versus unstimulated salivary flow rates.
Significant increase in parotid salivary flow rates (SFR) in 19 of 25 patients after TENS. Males showed more salivary secretion compared to females. TENS showed to be effective in increasing the SF rate in hyposalivatory patients with residual saliva.
Diabetes mellitus patients with xerostomia, N = 40
Tabletop TENS unit with surface electrode pads were placed externally in the skin overlying the parotid glands (anteroposteriorly between the tragus of the ear and the midmasseter region and superoinferiorly between the region of the head of the mandible and above the lower boarder of the mandible. The pulse rate was fixed at 50 Hz, and the intensity was gradually increased to a maximum tolerable level for each patient.
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Unstimulated saliva through the “low forced splitting” method and stimulated saliva collecting using TENS were assessed and compared. Long-term effects of TENS application were evaluated by recalling the patient 24 hours later.
A statistically significant increase in stimulated whole saliva after TENS application in continuous mode () was demonstrated compared with the unstimulated saliva, especially in xerostomia patients with diabetes. Burst mode inferred a statistically significant decrease in salivary flow (). In patients with diabetes with xerostomia and hyposalivation, TENS was highly effective in stimulating whole salivary flow.
TENS was adjusted with 50 Hz of frequency and 250 μs of pulse width intensity was adjusted over a 20-minute period according to maximum tolerance. The electrodes were placed bilaterally on the region of the salivary glands.
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Evaluation of the salivary flow was performed through sialometry before and immediately after application of TENS.
The most prevalent region for RT was the oropharynx (80% of cases). The mean dose used in RT was 64,6 ± 7,24 Gy. After TENS, salivary flow increased significantly () from 0.05 mL/min to 0.01 mL/min. The response to TENS was directly correlated with the intensity of the tolerated electric current (r = 0.553; ) and the dose used in RT (r = −0.514; ). TENS was able to increase the salivary flow rate of patients with RT-induced hyposalivation.
GenNarino contains an electronic circuit with a microprocessor, a pair of stimulation electrodes, and two 3 V 30 mAmp/h batteries. The electrodes contact the oral mucosa in the mandibular third molar area, close to the lingual nerve on one side. The electrical stimulation is of low intensity and not felt by the patient. In this trial, the stimulation signals were pulse-trains at 5 Hz, biphasic, at rectangular pulses of 1 mSec, with an output of 150 µA.
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The whole saliva flow rates were measured.
All the three subjects developed the capacity to spit saliva, not only in direct response to the electrostimulation but also after free intervals without electrostimulation. In addition, their symptoms of dry mouth severity and frequency improved. For all three subjects, no significant changes in the vital signs and in the oral mucosal status were observed.
Control group received a 50 μs, 2 Hz TENS at acupoints ST6 and TE17 three times a week for 3 weeks
Whole salivary flow rate and dry mouth intensity were measured totally five times for both groups, at pretreatment, after 3, 6, and 9 TENS sessions, and one week after the treatment was completed.
After 6 TENS sessions were completed, whole salivary flow rates increased stably until the end of 9 TENS sessions for the treatment group. In the follow-up week after treatment, there was significant increase as well. However, significant improvement in dry mouth intensity was observed at all posttests than that at pretreatment in both groups. Whole salivary flow rates and dry mouth intensity improving were only observed during and one week after the TENS sessions.
TENS group (n = 37) received 8 sessions (20 minutes each) delivered twice a week for four weeks. The electrodes were attached over the skin covering the salivary glands. The electric pulse was adjusted at a frequency of 50 hz, pulse width of 250 μs. and as intense as tolerated.
Participants in the control group (N = 31) received habitual care
SSF was evaluated through sialometry. Self‐perception of salivary flow (SPSF) and quality of life (QL) was evaluated prior to, during, and at 1, 3, and 6 months after treatment.
Although no changes were observed in the control group for SSF at any timepoints, TENS group showed a progressive increase in SSF from the third session until the end of the treatment. Significant improvements were also found in SPSF, especially when the SSF reached values ≥ 0.7 mL/minute. The most expressive results were evident at 6 months after treatment so that SSF, SPSF, and QL remained significantly higher (F = 9.5, ;H = 143.77, ;χ2 = 9.162, , respectively). TENS was effective at improving hyposalivation.
Diabetes mellitus type 2 patients with hyposalivation, N = 100, age range from 43 to 76 years
Randomly distributed to one experimental group, receiving one extra-oral 5 minutes TENS session, applied bilaterally on skin over parotid gland with frequency 50 Hz and pulse duration 250 μs.
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Unstimulated saliva was collected for 5 minutes immediately after the session, using the low forced spitting method. Stimulated saliva was collected during TENS application in graduated test tube.
90 out of 100 patients responded positively to TENS by increasing salivary volume and flow rate.
Patients treated with radiotherapy with or without chemotherapy for head and neck cancer (N = 30), with at least grade 1 or 2 symptomatic dry mouth
Patients randomly assigned to receive ALTENS four-times weekly for 6 weeks or two times weekly for 12 weeks.
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XeQoLS was administered at 6, 9, 15, and 21 months from the start of ALTENS treatment. A linear model was used to model the overall XeQoLS score at the 15-month endpoint.
This study demonstrates that both ALTENS regimens are safe, well tolerated, and appear to be equally effective.
Electrical stimulation was applied at constant strength for 60 minutes to the suprahyoid muscles using VitalStim®.
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Participants examined under three conditions of NMES: Sensory threshold plus 75% of the difference between sensory and pain thresholds (75% stim), SensoryStim, and sham. Saliva collections, using a 10-min spitting method, were performed seven times: Before stimulation (S1), during stimulation (S2–S6), and 5 min after stimulation ended (S7).
Increase in saliva flow was promoted after NMES. Therefore, NMES may have effects on patients with xerostomia.
