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The effectiveness of iontophoresis in reducing dentin hypersensitivity
A double-blind study compares the desensitizing effects of iontophoresis with sodium fluoride, iontophoresis with distilled water, sodium fluoride without iontophoresis, and distilled water without iontophoresis.
The effectiveness of iontophoresis in reducing dentin hypersensitivity Kathleen M . Brough, RD H, M S Dale M. Anderson, DDS John Love, DDS Pam ela R. Overm an, RD H, M S
entin hypersensitivity is common in adults, presenting problems to both the patient and the dentist. The pain as sociated w ith dentin hypersensitivity may vary in degree from a small amount of sensitivity to excruciating p a in .1 Hypersensitivity occurs when the den tinal tubules are exposed to external sources of irritation.2'3Abrasion, erosion, leaking margins of restorations, and den tal caries can cause dentin hypersensi tivity.2,3 In addition, dentin hypersensi tivity can result from gingival recession or periodontal therapy.4,s Several hypotheses have been formu lated concerning the m echanism of dentin hypersensitivity.5,7 The hydrod y nam ic theory of Brannstrom and others8,9 is currently the most widely ac cepted hypothesis regarding dentin hypersensitivity. The studies of Brann strom and others8,9 have shown that fluid within the dentinal tubules will expand or contract when certain stim uli are applied. Their hypothesis further con tends that the fluid allows movement of the odontoblasts, which stimulates the
unmyelinated efferent nerve endings of the dental pulp.8,9 Extensive research has been done on the treatment of hypersensitive dentin, but no one treatment has been accepted universally. The process of influencing ionic motion by electrical currents is known as electrophoresis, cataphoresis, or iontophoresis.10 The use of electrical currents may enhance ion uptake by the dentinal tubules and aid in achieving de sensitization. A number of studies have
Fig 1 ■ Iontophoresis unit, positive and negative electrodes, and test solutions used in the study.
tested iontophoresis and fluoride as de sensitizing agents. Murthy and others11 and Lutkins and others12 reported a re duction in sensitivity to both mechanical and thermal stim ulation w ith io n to phoresis and fluoride. However, Minkov and others3 reported conflicting results. The studies of Minkov and others suggest that no significant difference exists be tween 2% sodium fluoride used with or without iontophoresis in reducing den tin hypersensitivity. Gangarosa and others13'15 have reported a significant re duction in sensitivity with the use of iontophoresis with 2% sodium fluoride and an iontophoresis device that they de veloped. Their studies were limited be cause of a lack of control groups, a nonblinded format, and a lack of statisti cal data. The purpose of the investigation reported in this article was to compare the desensitizing effects of iontophoresis with 2% sodium fluoride, iontophoresis with distilled water, 2% sodium fluoride w ithout iontophoresis, and distilled w ater w it h o u t io n to p h o r e s is in a double-blind study. JA D A , Vol. I l l , N ovem ber 1985 ■ 761
ARTI CLES
finger adaptation. Using a plastic elastic im random assignment, it appears that the teeth pression syringe and a starting temperature of treated w ith 2% sodium fluoride w ithout 20 C, the investigator flowed the water over the iontophoresis were sensitive at a lower tem exposed root surface until the response was perature. A three-factor repeated measures analysis of positive or for a maximum of 3 seconds. If the response was positive, that fact was recorded. variance was conducted to produce an error If the response was negative, the tooth was term for calculation of the Dunn’s Multiple retested with water at 10 C. The water tempera Comparison Test. Tables 3 and 4 show the ture was decreased at intervals of 10 degrees mean comparison results of the Dunn’s M ulti until a positive response was obtained, or until ple Comparison Test. To achieve a level of sig the testing system’s lim it was reached. The nificance, the mean differences had to be .58 pain-scoring system used was one that was (P < .05) or .67 (P < .01). A significant differ recommended by the ADA Council on Dental ence existed between the treatments of 2% Therapeutics for measuring dentin hyper sodium fluoride without iontophoresis and Fig 2 ■ Positive electrode was attached to forearm sensitivity. According to the system, the ther distilled water with iontophoresis at 2 weeks and connected to negative oral electrode. mal stimulus w ill or w ill not elicit a sensitive (P < .01) and at 4 weeks (P < .05). There also response (Edgar H. Mitchell, PhD, personal was a significant difference between the treat com m unication, A D A C ouncil on Dental ments of distilled water without iontophoresis Therapeutics). The highest temperature that and 2% sodium fluoride without iontophoresis elicited a response in each tooth was recorded. at 4 weeks (P < .05). Table 5 shows the mean differences within The electrode iontophoresis unit used during the study (Phoresor) was assembled according each group during the treatment. Comparison M ethods and m aterials of the four treatments discloses that sensitivity to the manufacturer’s specifications (Fig 1). to the cold stimulus decreased in all four Twelve patients, four males and eight females, This unit was chosen because of the amount of groups at the end of 1 month. Distilled water each having four hypersensitive teeth as a re voltage output produced. The unit used pro without iontophoresis was the only treatment sult of previous periodontal therapy or gingi duces up to 45 V, whereas the other ionto that had a significant effect in reducing sen val recession were enlisted from a university’s phoresis units available produce only 9 V. In sitivity to the cold stimulus at 1 week and con school of dentistry. The patients ranged in age theory, this higher voltage produces more elec tinued to be significant (P < .05) throughout from 22 to 49 years, with a mean age of 36.6 trons that can be driven toward the negative the study. The results disclosed that both source, or the tooth. years. A total of 48 sensitive facial surfaces, After baseline data were completed, the four groups that were treated with 2% sodium fluofour in each patient, were included in the study. Only patients who had the following teeth in each patient were assigned randomly to one of four treatment groups. The treatments were included in the study: were iontophoresis and 2% sodium fluoride, — four teeth hypersensitive to a cold iontophoresis and distilled water, 2% sodium stimulus (0 to 20 C); — no previous treatment done for hypersen fluoride without iontophoresis, and distilled water w ith o u t iontophoresis. To assure sitivity; — no restorations placed within the past 6 examiner blindness, the treatment code re mained sealed until the conclusion of the months on the hypersensitive teeth; —hypersensitivity located on the facial sur study. The four treatments were applied by the investigator. To maintain examiner blindness, face; — no caries or restorations in the area of the the test solutions and electrode iontophoresis unit (Phoresor) were placed behind a screen. hypersensitive teeth; The teeth were isolated with a rubber dam, — no systemic diseases; using finger adaptation, and dried with 2- x — no pacemaker; — willingness to sign a consent form ap 2-inch gauze before the application of treat proved by the University Human Experimenta ment. A cotton pledget, saturated with the test Fig 3 ■ Technique used during application of four solution, was placed into the plastic tip con tion Board; and treatments is shown. — a desire to participate in the study for 1 nected to the oral electrode and applied to the sensitive root surface for 2 minutes (Fig 2, 3). month. Thermal stimulation was used to quantitate The research assistant then recorded the tooth ride significantly reduced the patient’s re the patient’s sensitivity response. A thermal number, test solution, and whether 0 or .5 mA sponse to the cold stimulus at 2 and 4 weeks. testing technique developed by Johnson and of current was used. After all four teeth were Two percent sodium fluoride used with or others16 was modified to evaluate the patient’s treated, the investigator recorded the patient’s without iontophoresis was significant in re response to a cold stimulus. The degree of immediate response to the different tempera ducing sensitivity to the cold stimulus at theP hypersensitivity was determined through the tures of water used with the same measure < .01 level at the end of 4 weeks. use of different temperatures of water placed ment procedure. Measurements were repeated directly on the exposed root surfaces. The in and recorded 1,2, and 4 weeks after treatment. vestigator filled three thermal insulated con The data were analyzed with the use of a re tainers with water and regulated the tempera peated measures analysis of variance and Discussion ture by adding ice or hot water. The water Dunn’s Multiple Comparison Test. temperatures in each container then were ad One of the inherent problems of desen justed to 20 C, 10C, and 0C, which were easy to sitizing studies is in the development of a maintain. Each container held a thermometer Results technique and stimulus that w ill quantify to monitor the water temperature and a dispos able plastic elastic impression syringe. The To analyze the data, the responses of the pa reliably a patient’s response to pain. syringe was im m ersed in the container tient to the test temperatures were assigned a Studies performed by Overman,18 Minthroughout the treatment period and was re ranking of 4, 3, 2, or 1, if the tooth tested was kov and others,3 and Murthy and others11 moved just before its application to the tooth. unsensitive at 20 C, 10 C, 0 C, or the lowest test used mechanical stimulation to elicit a This technique was used because the equip temperature, respectively (Table 1). Baseline hypersensitive response. They scratched ment was relatively inexpensive and could be temperature sensitivity varied with each tooth. the exposed dentin with an explorer. This reproduced easily. Table 2 lists the means and standard devia introduces discrepancies in the study as Before baseline data were obtained, each tions of the ranking of the patient’s response to tooth was polished with a porte-polisher and a the test temperatures. Baseline means were no control exists over the amount of pres dentifrice that did not contain fluoride and had similar for each treatment except for the treat sure that is applied to the tooth surface. low abrasiveness.17 The teeth then were iso ment of 2% sodium fluoride without ionto Studies by Gangarosa and Park,13 Jen lated with a rubber dam without a clamp, using phoresis, which had a lower mean. In spite of sen,19 and Tarbet and others,20 used a 762 ■ JA D A , V ol. I l l , N ovem ber 1985
ART I CL E S
Table 1 ■ Frequency of teeth in each treatment versus patient response. Treatment Iontophoresis with 2% sodium fluoride
Iontophoresis with distilled water
Two percent sodium fluoride without iontophoresis
Distilled water without iontophoresis
Observation interval Baseline Immediate 1 week 2 weeks 4 weeks Baseline Immediate 1 week 2 weeks 4 weeks Baseline Immediate 1 week 2 weeks 4 weeks Baseline Immediate 1 week 2 weeks 4 weeks
4*
3*
2*
1*
9 8 7 4 4
3 4 4 4 3
0 0 1 3 4
0 0 0 1 1
9 7 9 7 5 4 5 5 2 2 9 4 5 4 4
2 3 1 3 3 7 5 3 5 5 3 7 4 6 5
1 2 1 2 4 1 1 4 4 2 0 1 3 2 3
0 0 1 0 0 0 1 0 1 3 0 0 0 0 0
*4 = 20 C; 3 = 10 C; 2 = 0 C; 1 = u nsensitive to lowest test tem perature.
blast of cold air. This technique does not confine the stimulus to the tooth surface and the air temperature can vary. More recent studies have attempted to quantify the stimulus with various regulating de vices. Tarbet and others21 used a dental pulp stethoscope. They stated that this device quantified the patient’s response to the electrical stim ulus and had a greater ability to discriminate changes in the patient’s response to pain. Their tech nique used the dental pulp stethoscope on the midgingival third of the enamel, whereas hypersensitivity usually occurs on the root surface and on exposed den tin. Placement of the probe tip in this manner may not elicit a true hypersensi tive response. Lutkins and others12used a direct contact probe that could be ad justed to varying temperatures when placed on the tooth. This device gives a precise reading but is extremely expen sive. In the present study, the technique used enabled the investigator to confine the stimulus to the tooth being tested, was reproducible, was inexpensive, and could simulate the irritation of a cold stimulus within a realistic temperature range. Also, it is difficult to monitor the clas sification of the patient’s response as “none,” “m ild,” “moderate,” “severe,” or “extreme.” During this investigation, an attempt was made to control for subjec tive responses by asking the participant merely to report whether the tooth was or was not painful. This eliminated the pa tient’s having to classify the pain. The present study determined that a significant difference existed between the four treatment groups and their responses to the cold stimulus. All mean values de creased compared with baseline values,
with a significant decrease in the pa tient’s response to the cold stimulus with iontophoresis and distilled water at 4 weeks. This finding compares favorably with that of Murthy and others,11 who conducted a double-blind study that compared iontophoresis with 1% sodium fluoride, the patient’s saliva, and 33.3% sodium fluoride. During their study, they reported a 35.13% reduction in the pain response at 2 and at 4 weeks in patients treated with iontophoresis and saliva. They attributed this effect to the forma tion of secondary dentin induced by the electric current. The study of Murthy and others11 also
that 64% of the patients treated with one application of 2% sodium fluoride and iontophoresis had a reduction in sensitiv ity and that the reduction can last from 3 months to 3 years. The latter study was lim ite d by design in that it lacked examiner blindness. Several hypotheses have been proposed to e x plain the claimed desensitizing effect of ionto phoresis. These include formation of sec ondary dentin, paresthesia of the odonto blastic processes, and blockage of the dentinal tubules by microprecipitation of calcium fluoride. A comparison of 2% sodium fluoride with and without iontophoresis shows that the use of fluoride alone was as effec tive in reducing sensitivity to the cold stimulus at 2 weeks as it was at 4 weeks. Previous studies have suggested that flu oride used as a dentifrice or in a concen trated solution is effective in reducing hypersensitivity.1,22,23 This finding com pares favorably with the finding of Minkov an d others,3 w ho co n d uc te d a d o u b le - b lin d stud y c o m p a rin g 2% sodium fluoride with and without ionto phoresis. At 4 weeks and at the comple tion of their 8-month study, they found no significant difference between the two treatments. As the iontophoresis unit used in this study is relatively expensive, it appears that 2% sodium fluoride used alone may be a more economic way to treat dentin hypersensitivity. Distilled water served as the control during this study and was significant in reducing the sensitivity to the cold stimulus at 1 week, 2 weeks, and 4 weeks. This decrease in temperature response could be attributed to the formation of irritation dentin. Previous studies have
As the iontophoresis unit used in this study is relatively expensive, it appears that 2 % sodium fluoride used alone may be a m ore econom ic way to treat dentin hypersensitivity.
found that there was a significant reduc tion in the temperature to which the pa tients responded at 2 and at 4 weeks with 2% sodium fluoride and iontophoresis. Studies performed earlier by Gangarosa and others13,14 and Murthy and others11 found that iontophoresis with either 1% sodium fluoride or 2% sodium fluoride does reduce sensitivity. M urthy and others11 reported a 55% reduction in sen sitivity with 1% sodium fluoride at 2 and 4 weeks. Gangarosa and Park13 reported
suggested that when the tooth is exposed to a cold stimulus for an extended period irritation dentin w ill form.24 Levin and others25 and Overman19 also have re ported that sensitivity decreases when d istilled water is used alone. They suggested that the decrease in sensitivity may have occurred as a result of a psycho logical, placebo effect. A significant decrease was seen in the patient’s response to the cold stimulus in all four treatment groups from baseline to
Brough-O thers : EFFECTIVENESS OF IO N T O P H O R E S IS IN R E D U C IN G H Y P E R S E N S IT IV IT Y * 763
ART I CLE S
T ab le 2 ■ Means and standard deviations of ranking of patients’ responses to test
temperatures. Observation interval Treatment Iontophoresis with 2% sodium fluoride Iontophoresis with distilled water Two percent sodium fluoride without iontophoresis Distilled water without iontophoresis
Baseline
Immediate
1 week
2 weeks
4 weeks
3.75* (.45)+
3.66 (.49)
3.50 (.67)
2.91 (.99)
2.83 (1.02)
3.66 (.65)
3.41 (.79)
3.50 (1.00)
3.41 (.79)
3.08 (.90)
3.25 (.62)
3.16 (.93)
3.08 (.90)
2.66 (.88)
2.50 (1.08)
3.75 (.45)
3.25 (.62)
3.16 (.83)
3.16 (.71)
3.08 (.79)
*M e an. t S ta n d a r d d evia tio n.
T ab le 3 ■ Dunn Multiple Mean Comparison Test: at 2 weeks.
Iontophoresis with 2% sodium fluoride
Treatment
Iontophoresis with distilled water
Two percent sodium fluoride without iontophoresis
Distilled water without iontophoresis
.50
.25
.25
.75*
.25
Iontophoresis with 2% sodium fluoride Iontophoresis with distilled water Two percent sodium fluoride without iontophoresis Distilled water without iontophoresis
.50
*p < .01.
Table 4 ■ Dunn Multiple Mean Comparison Test: at 4 weeks.
Treatment
Iontophoresis with 2% sodium fluoride
Iontophoresis with 2% sodium fluoride Iontophoresis with distilled water Two percent sodium fluoride without iontophoresis Distilled water without iontophoresis
Iontophoresis with distilled water
Two percent sodium fluoride without iontophoresis
Distilled water without iontophoresis
.33
.25
.58*
0
.25
.58*
*P < .05.
Table 5 ■ Dunn Multiple Mean Comparison Test: results during treatment. Observation interval Treatment Iontophoresis with 2% sodium fluoride Iontophoresis with distilled water Two percent sodium fluoride without iontophoresis Distilled water without iontophoresis * p < .0 1 . t P < .05.
764 ■ JA D A , Vol. I l l , N ovem ber 1985
Baseline to immediate
Baseline to 1 week
Baseline to 2 weeks
Baseline to 4 weeks
.09
.25
.84*
.92*
.25
.16
.25
.58+
.09
.17
.59+
.75*
.50
.58+
.58+
.66*
The technique used enabled the investigator to confine the stim ulus to the tooth being tested, was reproducible, was inexpensive, and could sim ulate the irritation of a cold stim ulus w ithin a realistic tem perature range.
1 month. Studies completed earlier have reported that a significant decrease in sensitivity occurred over time. These studies conclude that the desensitizing effect resulted from a gradual decrease in dentin permeability.26 Brannstrom and Garberoglio27 reported that saliva is ca pable of forming mineralized deposits that can become deposited within the ex posed dentin. Bacteria and their by products also have been found within the dentinal tubules. The bacteria embedded w ithin the tubules impede the movement of the fluid and the displacement of the od on to b lasts.28 Recent reports also suggest that components of saliva and plasma may be capable of decreasing den tin permeability.29 Poor oral hygiene frequently has been related to the presence of hypersensiti vity. It has been suggested by many clini cians that improving oral hygiene gradu ally w ill d im in ish tooth sensitivity. During this study, the patients were not given any oral hygiene instruction be cause the effect of home care instruction in reducing sensitivity was not being evaluated. One limitation of this study was the short observation time after treatment. The sample size was relatively small. Baseline mean scores were unequal to random assignment. Future investiga tions may have to forfeit randomization in favor of equal baseline temperatures for each group. During the course of this in vestigation, only one treatment was applied on each tooth. The manufacturer of the iontophoresis unit used states that it may take up to three treatments to achieve desensitization. Future investi gations should apply more than one treatment and observe the patient’s re sponse for a longer time after treatment. C on clu sio n s The following conclusions can be drawn from this study: — One application of distilled water w ith iontophoresis significantly de creases the patient’s response to the cold stimulus after 4 weeks. — One application of 2% sodium fluo ride with iontophoresis significantly de creases the patient’s response to the cold stimulus after 2 and 4 weeks. — One application of 2% sodium fluo
ride without iontophoresis significantly reduces the patient’s response to the cold stimulus after 2 and 4 weeks. — Comparison of one application of 2% sodium fluoride with or without ionto phoresis suggests that no significant dif ference exists between the two treatments in reducing the patient’s response to the cold stimulus. — One application of distilled water without iontophoresis significantly re duces the patient’s response to the cold stimulus after 1, 2, and 4 weeks and ap pears to have the most significant im mediate and long-term effect. — A significant decrease occurs in the patient’s response to the cold stimulus with each of the treatments with the pas sage of time. ----------------------------------------------- JA D A The authors know of no commercial connection to the products used in the study and do not have any commercial interests in the products at the present time. The informed consent of all human subjects who participated in the experimental investigation re ported or described in this manuscript was obtained after the nature of the procedure and possible discom forts and risks had been fully explained. This research was supported by the Rinehart Foun dation through the UMKC Project Review and Grants Committee, University of Missouri-Kansas City, School of Dentistry. The authors thank Dan Tira, PhD, for his assistance. Ms. Brough is assistant professor, dental hygiene, department of associated dental sciences, Medical College of Georgia, Augusta, GA 30912. Dr. Anderson is chairman, department of endodontics; Dr. Love is associate professor of periodontics; and Ms. Overman is director, department of dental hygiene, University of Missouri-Kansas City, School of Dentistry, Kansas City, MO. Address requests for reprints to Dr. Brough. 1. Stout, W.C. Sodium silicofluoride as a desen sitizing agent. J Periodontol 26(3):208-210, 1955. 2. Peden, J. Dental hypersensitivity. J West Soc Periodont/Periodont Abstracts 25(2):75-83, 1977. 3. Minkov, B., and others. Effectiveness of sodium fluoride treatment with and without iontophoresis on the reduction of hypersensitive dentin. J Periodontol 46(4):236-249, 1975. 4. Grant, D.A.; Stern, I.B.; and Everett, F.G. Plaque control (oral hygiene) and gingival massage, root sen sitivity, and halitosis. Periodontics. St. Louis, C. V. Mosby Co, 1979, pp 527-570. 5. Carranza, F.A. General principles of periodontal surgery. G lic km a n ’s c lin ical periodontology. Philadelphia, W. B. Saunders Co, 1984, pp 761-772. 6. Seltzer, S. Dental conditions that cause head and neck pain. Pain control in dentistry. Philadelphia, J.
B. Lippincott Co, 1978, pp 105-136. 7. Roane, J.B., and others. An ultrastructural study of dentinal innervation in the adult human tooth. Oral Surg 35(1):94-104, 1973. 8. Brannstrom, M., and Astrom, A. The hydro dynamics of dentin: its possible relationship to den tinal pain. Int Dent J 22(2):219-227, 1972. 9. Brannstrom, M.; Linden, L.A.; and Astrom, A. The hydrodynamics of the dental tubule and of pulp fluid. Caries Res 1(4):310-317, 1967. 10. Scott, H.M. Reduction of sensitivity by electro phoresis. ASDC J Dent Child 29(4):225-241, 1962. 11. Murthy, K.S.; Talim, S.T.; and Singh, I. A com parative evaluation of topical application and ionto phoresis of sodium fluoride for desensitization of hypersensitive dentin. Oral Surg 36(3):448-458,1973. 12. Lutkins, W.D.; Greco, G.W.; and McFall, W.T., Jr. Effectiveness of sodium fluoride on tooth hyper sensitivity with and w ithout iontophoresis. J Periodontol 55(5):285-288, 1984. 13. Gangarosa, L.P., and Park, N.H. Practical con siderations in iontophoresis of fluoride for desensitiz ing dentin. J Prosthet Dent 39(2):173-178, 1978. 14. Gangarosa, L.P., and others. Desensitizing hy persensitive dentin by iontophoresis with fluoride. NY State Dent J 43(3):92-94, 1978. 15. Gangarosa, L.P. Iontophoresis in dental prac tice. Chicago, Quintessence Publishing Co, Inc, 1983. 16. Johnson, R.H.; Zulgar-Nain, B.J.; and Koval, J.J. The effectiveness of an electro-ionozing toothbrush in the control of dentinal hypersensitivity. J Periodontol 53(6):353-359, 1982. 17. Council of Dental Therapeutics. Dentifrices, mouthwashes, and oxygenating agents. Accepted dental therapeutics, ed 39. Chicago, American Dental Association, 1982, p 376. 18. Overman, P.R. Calcium hypophosphate as a root desensitizing agent. Dent Hyg 57(8):30-35,1983. 19. Jensen, A.L. Hypersensitivity controlled by iontophoresis: double blind clinical investigation. JADA 68(2):216-225, 1964. 20. Tarbet, W.J., and others. Clinical evaluation of a new treatment for dentinal hypersensitivity. J Periodontol, 1980. 21. Tarbet, W.J., and others. An evaluation of two methods for the quantitation of dentinal hypersensi tivity. JADA 98(6):914-918, 1979. 22. Hoyt, W.H., and Bibby, B.G. Use of sodium fluoride for desensitizing dentin. JADA 30(3):13721376,1943. 23. Kanouse, M.C., and Ash, M.M., Jr. The effec tiveness of sodium monofluorophosphate dentifrice on dental hypersensitivity. J Periodontol 40(l):38-39, 1969. 24. Dowden, W.E.; Emmings, F.; and Langeland, K. The pulpal effect of freezing temperatures applied to monkey teeth. Oral Surg 55(4):408-418, 1983. 25. Levin, M.P.; Yearwood, L.L.; and Carpenter, W.N. The desensitizing effect of calcium hydroxide and magnesium hydroxide on hypersensitive dentin. Oral Surg 35(5):741-746, 1973. 26. Pashley, D.H., and others. Dentin permeability: effects of desensitizing dentifrices in vitro. J Periodontol 55(9):522-524, 1984. 27. Brannstrom, M., and Garberoglio, R. Occlusion of dentinal tubules under superficial attrited dentin. Swed Dent J 4(3):87-91, 1980. 28. Michelich, V.; Schuster, G.S.; and Pashley, D.H. Bacterial penetration of human dentin in vitro. J Dent Res 59(8):1398-1403, 1980. 29. Pashley, D.H.; Nelson, R.; and Kepler, E.E. The effects of plasma and salivary constituents on dentin permeability. J Dent Res 61(8):978-981, 1982.
B rough-O thers : EFFECTIVENESS OF IO N T O P H O R E S IS IN R E D U C IN G H Y P E R S E N S IT IV IT Y ■ 765
The effectiveness of iontophoresis in reducing dentin hypersensitivity Kathleen M . Brough, RD H, M S Dale M. Anderson, DDS John Love, DDS Pam ela R. Overm an, RD H, M S
entin hypersensitivity is common in adults, presenting problems to both the patient and the dentist. The pain as sociated w ith dentin hypersensitivity may vary in degree from a small amount of sensitivity to excruciating p a in .1 Hypersensitivity occurs when the den tinal tubules are exposed to external sources of irritation.2'3Abrasion, erosion, leaking margins of restorations, and den tal caries can cause dentin hypersensi tivity.2,3 In addition, dentin hypersensi tivity can result from gingival recession or periodontal therapy.4,s Several hypotheses have been formu lated concerning the m echanism of dentin hypersensitivity.5,7 The hydrod y nam ic theory of Brannstrom and others8,9 is currently the most widely ac cepted hypothesis regarding dentin hypersensitivity. The studies of Brann strom and others8,9 have shown that fluid within the dentinal tubules will expand or contract when certain stim uli are applied. Their hypothesis further con tends that the fluid allows movement of the odontoblasts, which stimulates the
unmyelinated efferent nerve endings of the dental pulp.8,9 Extensive research has been done on the treatment of hypersensitive dentin, but no one treatment has been accepted universally. The process of influencing ionic motion by electrical currents is known as electrophoresis, cataphoresis, or iontophoresis.10 The use of electrical currents may enhance ion uptake by the dentinal tubules and aid in achieving de sensitization. A number of studies have
Fig 1 ■ Iontophoresis unit, positive and negative electrodes, and test solutions used in the study.
tested iontophoresis and fluoride as de sensitizing agents. Murthy and others11 and Lutkins and others12 reported a re duction in sensitivity to both mechanical and thermal stim ulation w ith io n to phoresis and fluoride. However, Minkov and others3 reported conflicting results. The studies of Minkov and others suggest that no significant difference exists be tween 2% sodium fluoride used with or without iontophoresis in reducing den tin hypersensitivity. Gangarosa and others13'15 have reported a significant re duction in sensitivity with the use of iontophoresis with 2% sodium fluoride and an iontophoresis device that they de veloped. Their studies were limited be cause of a lack of control groups, a nonblinded format, and a lack of statisti cal data. The purpose of the investigation reported in this article was to compare the desensitizing effects of iontophoresis with 2% sodium fluoride, iontophoresis with distilled water, 2% sodium fluoride w ithout iontophoresis, and distilled w ater w it h o u t io n to p h o r e s is in a double-blind study. JA D A , Vol. I l l , N ovem ber 1985 ■ 761
ARTI CLES
finger adaptation. Using a plastic elastic im random assignment, it appears that the teeth pression syringe and a starting temperature of treated w ith 2% sodium fluoride w ithout 20 C, the investigator flowed the water over the iontophoresis were sensitive at a lower tem exposed root surface until the response was perature. A three-factor repeated measures analysis of positive or for a maximum of 3 seconds. If the response was positive, that fact was recorded. variance was conducted to produce an error If the response was negative, the tooth was term for calculation of the Dunn’s Multiple retested with water at 10 C. The water tempera Comparison Test. Tables 3 and 4 show the ture was decreased at intervals of 10 degrees mean comparison results of the Dunn’s M ulti until a positive response was obtained, or until ple Comparison Test. To achieve a level of sig the testing system’s lim it was reached. The nificance, the mean differences had to be .58 pain-scoring system used was one that was (P < .05) or .67 (P < .01). A significant differ recommended by the ADA Council on Dental ence existed between the treatments of 2% Therapeutics for measuring dentin hyper sodium fluoride without iontophoresis and Fig 2 ■ Positive electrode was attached to forearm sensitivity. According to the system, the ther distilled water with iontophoresis at 2 weeks and connected to negative oral electrode. mal stimulus w ill or w ill not elicit a sensitive (P < .01) and at 4 weeks (P < .05). There also response (Edgar H. Mitchell, PhD, personal was a significant difference between the treat com m unication, A D A C ouncil on Dental ments of distilled water without iontophoresis Therapeutics). The highest temperature that and 2% sodium fluoride without iontophoresis elicited a response in each tooth was recorded. at 4 weeks (P < .05). Table 5 shows the mean differences within The electrode iontophoresis unit used during the study (Phoresor) was assembled according each group during the treatment. Comparison M ethods and m aterials of the four treatments discloses that sensitivity to the manufacturer’s specifications (Fig 1). to the cold stimulus decreased in all four Twelve patients, four males and eight females, This unit was chosen because of the amount of groups at the end of 1 month. Distilled water each having four hypersensitive teeth as a re voltage output produced. The unit used pro without iontophoresis was the only treatment sult of previous periodontal therapy or gingi duces up to 45 V, whereas the other ionto that had a significant effect in reducing sen val recession were enlisted from a university’s phoresis units available produce only 9 V. In sitivity to the cold stimulus at 1 week and con school of dentistry. The patients ranged in age theory, this higher voltage produces more elec tinued to be significant (P < .05) throughout from 22 to 49 years, with a mean age of 36.6 trons that can be driven toward the negative the study. The results disclosed that both source, or the tooth. years. A total of 48 sensitive facial surfaces, After baseline data were completed, the four groups that were treated with 2% sodium fluofour in each patient, were included in the study. Only patients who had the following teeth in each patient were assigned randomly to one of four treatment groups. The treatments were included in the study: were iontophoresis and 2% sodium fluoride, — four teeth hypersensitive to a cold iontophoresis and distilled water, 2% sodium stimulus (0 to 20 C); — no previous treatment done for hypersen fluoride without iontophoresis, and distilled water w ith o u t iontophoresis. To assure sitivity; — no restorations placed within the past 6 examiner blindness, the treatment code re mained sealed until the conclusion of the months on the hypersensitive teeth; —hypersensitivity located on the facial sur study. The four treatments were applied by the investigator. To maintain examiner blindness, face; — no caries or restorations in the area of the the test solutions and electrode iontophoresis unit (Phoresor) were placed behind a screen. hypersensitive teeth; The teeth were isolated with a rubber dam, — no systemic diseases; using finger adaptation, and dried with 2- x — no pacemaker; — willingness to sign a consent form ap 2-inch gauze before the application of treat proved by the University Human Experimenta ment. A cotton pledget, saturated with the test Fig 3 ■ Technique used during application of four solution, was placed into the plastic tip con tion Board; and treatments is shown. — a desire to participate in the study for 1 nected to the oral electrode and applied to the sensitive root surface for 2 minutes (Fig 2, 3). month. Thermal stimulation was used to quantitate The research assistant then recorded the tooth ride significantly reduced the patient’s re the patient’s sensitivity response. A thermal number, test solution, and whether 0 or .5 mA sponse to the cold stimulus at 2 and 4 weeks. testing technique developed by Johnson and of current was used. After all four teeth were Two percent sodium fluoride used with or others16 was modified to evaluate the patient’s treated, the investigator recorded the patient’s without iontophoresis was significant in re response to a cold stimulus. The degree of immediate response to the different tempera ducing sensitivity to the cold stimulus at theP hypersensitivity was determined through the tures of water used with the same measure < .01 level at the end of 4 weeks. use of different temperatures of water placed ment procedure. Measurements were repeated directly on the exposed root surfaces. The in and recorded 1,2, and 4 weeks after treatment. vestigator filled three thermal insulated con The data were analyzed with the use of a re tainers with water and regulated the tempera peated measures analysis of variance and Discussion ture by adding ice or hot water. The water Dunn’s Multiple Comparison Test. temperatures in each container then were ad One of the inherent problems of desen justed to 20 C, 10C, and 0C, which were easy to sitizing studies is in the development of a maintain. Each container held a thermometer Results technique and stimulus that w ill quantify to monitor the water temperature and a dispos able plastic elastic impression syringe. The To analyze the data, the responses of the pa reliably a patient’s response to pain. syringe was im m ersed in the container tient to the test temperatures were assigned a Studies performed by Overman,18 Minthroughout the treatment period and was re ranking of 4, 3, 2, or 1, if the tooth tested was kov and others,3 and Murthy and others11 moved just before its application to the tooth. unsensitive at 20 C, 10 C, 0 C, or the lowest test used mechanical stimulation to elicit a This technique was used because the equip temperature, respectively (Table 1). Baseline hypersensitive response. They scratched ment was relatively inexpensive and could be temperature sensitivity varied with each tooth. the exposed dentin with an explorer. This reproduced easily. Table 2 lists the means and standard devia introduces discrepancies in the study as Before baseline data were obtained, each tions of the ranking of the patient’s response to tooth was polished with a porte-polisher and a the test temperatures. Baseline means were no control exists over the amount of pres dentifrice that did not contain fluoride and had similar for each treatment except for the treat sure that is applied to the tooth surface. low abrasiveness.17 The teeth then were iso ment of 2% sodium fluoride without ionto Studies by Gangarosa and Park,13 Jen lated with a rubber dam without a clamp, using phoresis, which had a lower mean. In spite of sen,19 and Tarbet and others,20 used a 762 ■ JA D A , V ol. I l l , N ovem ber 1985
ART I CL E S
Table 1 ■ Frequency of teeth in each treatment versus patient response. Treatment Iontophoresis with 2% sodium fluoride
Iontophoresis with distilled water
Two percent sodium fluoride without iontophoresis
Distilled water without iontophoresis
Observation interval Baseline Immediate 1 week 2 weeks 4 weeks Baseline Immediate 1 week 2 weeks 4 weeks Baseline Immediate 1 week 2 weeks 4 weeks Baseline Immediate 1 week 2 weeks 4 weeks
4*
3*
2*
1*
9 8 7 4 4
3 4 4 4 3
0 0 1 3 4
0 0 0 1 1
9 7 9 7 5 4 5 5 2 2 9 4 5 4 4
2 3 1 3 3 7 5 3 5 5 3 7 4 6 5
1 2 1 2 4 1 1 4 4 2 0 1 3 2 3
0 0 1 0 0 0 1 0 1 3 0 0 0 0 0
*4 = 20 C; 3 = 10 C; 2 = 0 C; 1 = u nsensitive to lowest test tem perature.
blast of cold air. This technique does not confine the stimulus to the tooth surface and the air temperature can vary. More recent studies have attempted to quantify the stimulus with various regulating de vices. Tarbet and others21 used a dental pulp stethoscope. They stated that this device quantified the patient’s response to the electrical stim ulus and had a greater ability to discriminate changes in the patient’s response to pain. Their tech nique used the dental pulp stethoscope on the midgingival third of the enamel, whereas hypersensitivity usually occurs on the root surface and on exposed den tin. Placement of the probe tip in this manner may not elicit a true hypersensi tive response. Lutkins and others12used a direct contact probe that could be ad justed to varying temperatures when placed on the tooth. This device gives a precise reading but is extremely expen sive. In the present study, the technique used enabled the investigator to confine the stimulus to the tooth being tested, was reproducible, was inexpensive, and could simulate the irritation of a cold stimulus within a realistic temperature range. Also, it is difficult to monitor the clas sification of the patient’s response as “none,” “m ild,” “moderate,” “severe,” or “extreme.” During this investigation, an attempt was made to control for subjec tive responses by asking the participant merely to report whether the tooth was or was not painful. This eliminated the pa tient’s having to classify the pain. The present study determined that a significant difference existed between the four treatment groups and their responses to the cold stimulus. All mean values de creased compared with baseline values,
with a significant decrease in the pa tient’s response to the cold stimulus with iontophoresis and distilled water at 4 weeks. This finding compares favorably with that of Murthy and others,11 who conducted a double-blind study that compared iontophoresis with 1% sodium fluoride, the patient’s saliva, and 33.3% sodium fluoride. During their study, they reported a 35.13% reduction in the pain response at 2 and at 4 weeks in patients treated with iontophoresis and saliva. They attributed this effect to the forma tion of secondary dentin induced by the electric current. The study of Murthy and others11 also
that 64% of the patients treated with one application of 2% sodium fluoride and iontophoresis had a reduction in sensitiv ity and that the reduction can last from 3 months to 3 years. The latter study was lim ite d by design in that it lacked examiner blindness. Several hypotheses have been proposed to e x plain the claimed desensitizing effect of ionto phoresis. These include formation of sec ondary dentin, paresthesia of the odonto blastic processes, and blockage of the dentinal tubules by microprecipitation of calcium fluoride. A comparison of 2% sodium fluoride with and without iontophoresis shows that the use of fluoride alone was as effec tive in reducing sensitivity to the cold stimulus at 2 weeks as it was at 4 weeks. Previous studies have suggested that flu oride used as a dentifrice or in a concen trated solution is effective in reducing hypersensitivity.1,22,23 This finding com pares favorably with the finding of Minkov an d others,3 w ho co n d uc te d a d o u b le - b lin d stud y c o m p a rin g 2% sodium fluoride with and without ionto phoresis. At 4 weeks and at the comple tion of their 8-month study, they found no significant difference between the two treatments. As the iontophoresis unit used in this study is relatively expensive, it appears that 2% sodium fluoride used alone may be a more economic way to treat dentin hypersensitivity. Distilled water served as the control during this study and was significant in reducing the sensitivity to the cold stimulus at 1 week, 2 weeks, and 4 weeks. This decrease in temperature response could be attributed to the formation of irritation dentin. Previous studies have
As the iontophoresis unit used in this study is relatively expensive, it appears that 2 % sodium fluoride used alone may be a m ore econom ic way to treat dentin hypersensitivity.
found that there was a significant reduc tion in the temperature to which the pa tients responded at 2 and at 4 weeks with 2% sodium fluoride and iontophoresis. Studies performed earlier by Gangarosa and others13,14 and Murthy and others11 found that iontophoresis with either 1% sodium fluoride or 2% sodium fluoride does reduce sensitivity. M urthy and others11 reported a 55% reduction in sen sitivity with 1% sodium fluoride at 2 and 4 weeks. Gangarosa and Park13 reported
suggested that when the tooth is exposed to a cold stimulus for an extended period irritation dentin w ill form.24 Levin and others25 and Overman19 also have re ported that sensitivity decreases when d istilled water is used alone. They suggested that the decrease in sensitivity may have occurred as a result of a psycho logical, placebo effect. A significant decrease was seen in the patient’s response to the cold stimulus in all four treatment groups from baseline to
Brough-O thers : EFFECTIVENESS OF IO N T O P H O R E S IS IN R E D U C IN G H Y P E R S E N S IT IV IT Y * 763
ART I CLE S
T ab le 2 ■ Means and standard deviations of ranking of patients’ responses to test
temperatures. Observation interval Treatment Iontophoresis with 2% sodium fluoride Iontophoresis with distilled water Two percent sodium fluoride without iontophoresis Distilled water without iontophoresis
Baseline
Immediate
1 week
2 weeks
4 weeks
3.75* (.45)+
3.66 (.49)
3.50 (.67)
2.91 (.99)
2.83 (1.02)
3.66 (.65)
3.41 (.79)
3.50 (1.00)
3.41 (.79)
3.08 (.90)
3.25 (.62)
3.16 (.93)
3.08 (.90)
2.66 (.88)
2.50 (1.08)
3.75 (.45)
3.25 (.62)
3.16 (.83)
3.16 (.71)
3.08 (.79)
*M e an. t S ta n d a r d d evia tio n.
T ab le 3 ■ Dunn Multiple Mean Comparison Test: at 2 weeks.
Iontophoresis with 2% sodium fluoride
Treatment
Iontophoresis with distilled water
Two percent sodium fluoride without iontophoresis
Distilled water without iontophoresis
.50
.25
.25
.75*
.25
Iontophoresis with 2% sodium fluoride Iontophoresis with distilled water Two percent sodium fluoride without iontophoresis Distilled water without iontophoresis
.50
*p < .01.
Table 4 ■ Dunn Multiple Mean Comparison Test: at 4 weeks.
Treatment
Iontophoresis with 2% sodium fluoride
Iontophoresis with 2% sodium fluoride Iontophoresis with distilled water Two percent sodium fluoride without iontophoresis Distilled water without iontophoresis
Iontophoresis with distilled water
Two percent sodium fluoride without iontophoresis
Distilled water without iontophoresis
.33
.25
.58*
0
.25
.58*
*P < .05.
Table 5 ■ Dunn Multiple Mean Comparison Test: results during treatment. Observation interval Treatment Iontophoresis with 2% sodium fluoride Iontophoresis with distilled water Two percent sodium fluoride without iontophoresis Distilled water without iontophoresis * p < .0 1 . t P < .05.
764 ■ JA D A , Vol. I l l , N ovem ber 1985
Baseline to immediate
Baseline to 1 week
Baseline to 2 weeks
Baseline to 4 weeks
.09
.25
.84*
.92*
.25
.16
.25
.58+
.09
.17
.59+
.75*
.50
.58+
.58+
.66*
The technique used enabled the investigator to confine the stim ulus to the tooth being tested, was reproducible, was inexpensive, and could sim ulate the irritation of a cold stim ulus w ithin a realistic tem perature range.
1 month. Studies completed earlier have reported that a significant decrease in sensitivity occurred over time. These studies conclude that the desensitizing effect resulted from a gradual decrease in dentin permeability.26 Brannstrom and Garberoglio27 reported that saliva is ca pable of forming mineralized deposits that can become deposited within the ex posed dentin. Bacteria and their by products also have been found within the dentinal tubules. The bacteria embedded w ithin the tubules impede the movement of the fluid and the displacement of the od on to b lasts.28 Recent reports also suggest that components of saliva and plasma may be capable of decreasing den tin permeability.29 Poor oral hygiene frequently has been related to the presence of hypersensiti vity. It has been suggested by many clini cians that improving oral hygiene gradu ally w ill d im in ish tooth sensitivity. During this study, the patients were not given any oral hygiene instruction be cause the effect of home care instruction in reducing sensitivity was not being evaluated. One limitation of this study was the short observation time after treatment. The sample size was relatively small. Baseline mean scores were unequal to random assignment. Future investiga tions may have to forfeit randomization in favor of equal baseline temperatures for each group. During the course of this in vestigation, only one treatment was applied on each tooth. The manufacturer of the iontophoresis unit used states that it may take up to three treatments to achieve desensitization. Future investi gations should apply more than one treatment and observe the patient’s re sponse for a longer time after treatment. C on clu sio n s The following conclusions can be drawn from this study: — One application of distilled water w ith iontophoresis significantly de creases the patient’s response to the cold stimulus after 4 weeks. — One application of 2% sodium fluo ride with iontophoresis significantly de creases the patient’s response to the cold stimulus after 2 and 4 weeks. — One application of 2% sodium fluo
ride without iontophoresis significantly reduces the patient’s response to the cold stimulus after 2 and 4 weeks. — Comparison of one application of 2% sodium fluoride with or without ionto phoresis suggests that no significant dif ference exists between the two treatments in reducing the patient’s response to the cold stimulus. — One application of distilled water without iontophoresis significantly re duces the patient’s response to the cold stimulus after 1, 2, and 4 weeks and ap pears to have the most significant im mediate and long-term effect. — A significant decrease occurs in the patient’s response to the cold stimulus with each of the treatments with the pas sage of time. ----------------------------------------------- JA D A The authors know of no commercial connection to the products used in the study and do not have any commercial interests in the products at the present time. The informed consent of all human subjects who participated in the experimental investigation re ported or described in this manuscript was obtained after the nature of the procedure and possible discom forts and risks had been fully explained. This research was supported by the Rinehart Foun dation through the UMKC Project Review and Grants Committee, University of Missouri-Kansas City, School of Dentistry. The authors thank Dan Tira, PhD, for his assistance. Ms. Brough is assistant professor, dental hygiene, department of associated dental sciences, Medical College of Georgia, Augusta, GA 30912. Dr. Anderson is chairman, department of endodontics; Dr. Love is associate professor of periodontics; and Ms. Overman is director, department of dental hygiene, University of Missouri-Kansas City, School of Dentistry, Kansas City, MO. Address requests for reprints to Dr. Brough. 1. Stout, W.C. Sodium silicofluoride as a desen sitizing agent. J Periodontol 26(3):208-210, 1955. 2. Peden, J. Dental hypersensitivity. J West Soc Periodont/Periodont Abstracts 25(2):75-83, 1977. 3. Minkov, B., and others. Effectiveness of sodium fluoride treatment with and without iontophoresis on the reduction of hypersensitive dentin. J Periodontol 46(4):236-249, 1975. 4. Grant, D.A.; Stern, I.B.; and Everett, F.G. Plaque control (oral hygiene) and gingival massage, root sen sitivity, and halitosis. Periodontics. St. Louis, C. V. Mosby Co, 1979, pp 527-570. 5. Carranza, F.A. General principles of periodontal surgery. G lic km a n ’s c lin ical periodontology. Philadelphia, W. B. Saunders Co, 1984, pp 761-772. 6. Seltzer, S. Dental conditions that cause head and neck pain. Pain control in dentistry. Philadelphia, J.
B. Lippincott Co, 1978, pp 105-136. 7. Roane, J.B., and others. An ultrastructural study of dentinal innervation in the adult human tooth. Oral Surg 35(1):94-104, 1973. 8. Brannstrom, M., and Astrom, A. The hydro dynamics of dentin: its possible relationship to den tinal pain. Int Dent J 22(2):219-227, 1972. 9. Brannstrom, M.; Linden, L.A.; and Astrom, A. The hydrodynamics of the dental tubule and of pulp fluid. Caries Res 1(4):310-317, 1967. 10. Scott, H.M. Reduction of sensitivity by electro phoresis. ASDC J Dent Child 29(4):225-241, 1962. 11. Murthy, K.S.; Talim, S.T.; and Singh, I. A com parative evaluation of topical application and ionto phoresis of sodium fluoride for desensitization of hypersensitive dentin. Oral Surg 36(3):448-458,1973. 12. Lutkins, W.D.; Greco, G.W.; and McFall, W.T., Jr. Effectiveness of sodium fluoride on tooth hyper sensitivity with and w ithout iontophoresis. J Periodontol 55(5):285-288, 1984. 13. Gangarosa, L.P., and Park, N.H. Practical con siderations in iontophoresis of fluoride for desensitiz ing dentin. J Prosthet Dent 39(2):173-178, 1978. 14. Gangarosa, L.P., and others. Desensitizing hy persensitive dentin by iontophoresis with fluoride. NY State Dent J 43(3):92-94, 1978. 15. Gangarosa, L.P. Iontophoresis in dental prac tice. Chicago, Quintessence Publishing Co, Inc, 1983. 16. Johnson, R.H.; Zulgar-Nain, B.J.; and Koval, J.J. The effectiveness of an electro-ionozing toothbrush in the control of dentinal hypersensitivity. J Periodontol 53(6):353-359, 1982. 17. Council of Dental Therapeutics. Dentifrices, mouthwashes, and oxygenating agents. Accepted dental therapeutics, ed 39. Chicago, American Dental Association, 1982, p 376. 18. Overman, P.R. Calcium hypophosphate as a root desensitizing agent. Dent Hyg 57(8):30-35,1983. 19. Jensen, A.L. Hypersensitivity controlled by iontophoresis: double blind clinical investigation. JADA 68(2):216-225, 1964. 20. Tarbet, W.J., and others. Clinical evaluation of a new treatment for dentinal hypersensitivity. J Periodontol, 1980. 21. Tarbet, W.J., and others. An evaluation of two methods for the quantitation of dentinal hypersensi tivity. JADA 98(6):914-918, 1979. 22. Hoyt, W.H., and Bibby, B.G. Use of sodium fluoride for desensitizing dentin. JADA 30(3):13721376,1943. 23. Kanouse, M.C., and Ash, M.M., Jr. The effec tiveness of sodium monofluorophosphate dentifrice on dental hypersensitivity. J Periodontol 40(l):38-39, 1969. 24. Dowden, W.E.; Emmings, F.; and Langeland, K. The pulpal effect of freezing temperatures applied to monkey teeth. Oral Surg 55(4):408-418, 1983. 25. Levin, M.P.; Yearwood, L.L.; and Carpenter, W.N. The desensitizing effect of calcium hydroxide and magnesium hydroxide on hypersensitive dentin. Oral Surg 35(5):741-746, 1973. 26. Pashley, D.H., and others. Dentin permeability: effects of desensitizing dentifrices in vitro. J Periodontol 55(9):522-524, 1984. 27. Brannstrom, M., and Garberoglio, R. Occlusion of dentinal tubules under superficial attrited dentin. Swed Dent J 4(3):87-91, 1980. 28. Michelich, V.; Schuster, G.S.; and Pashley, D.H. Bacterial penetration of human dentin in vitro. J Dent Res 59(8):1398-1403, 1980. 29. Pashley, D.H.; Nelson, R.; and Kepler, E.E. The effects of plasma and salivary constituents on dentin permeability. J Dent Res 61(8):978-981, 1982.
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