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Practical considerations in iontophoresis of fluoride for desensitizing dentin
Practical considerations in iontophoresis of fluoride for desensitizing dentin L. P. Gangarosa, Ph.D., D.D.S.,* and N. H. Park, D.D.S., M.S.D.** Medical College of Georgia, School of Dentistry, Augusta, Ca.
Two recent research reports have expressed a difference of opinion on the merit of desensitizing hypersensitive dentin by fluoride iontophoresis. I n 1973 Murthy and associates 1 reported on a doubleblind controlled study comparing the effectiveness of 1% sodium fluoride iontophoresis with the effectiveness of saliva iontophoresis and of the topical application of 33.3% sodium fluoride paste. The authors concluded that the application of fluoride ions under a negative electrode was the most effective means of dentin desensitization. More recently Minkov and associates 2 reported a significant decrease in the sensitivity of exposed cervical "dentin after twelve treatments over a 6 week period using a 2% sodium fluoride solution; the decrease occurred whether the solution was applied topically without current or under a positive electrode. Those dissenting articles induced us to review the literature on fluoride desensitization and describe an effective clinical method of attaining dentin desensitization by iontophoresis. LITERATURE REVIEW
The ideal dentin desensitizer. Grossman 3 suggested that the ideal desensitizer: (I) should not be undulyirritating to the pulp, (2)should be relatively painless, (3) should be easy to apply, (4) should be permanently effective, (5) should act quickly, (6) should be consistently effective, and (7) should not cause tooth discoloration. The agents currently in use should be evaluated according to these criteria; of the methods currently or previously in vogue none has fulfilled the ideal, but fluoride therapy appears to be the most promising method. Topical application of fluoride. In 1941 Lukom*Professor and Goordinator of Pharmacology, Departments of Oral Biology and Pharmacology. **Postdoctoral Fellow, Departments of Oral Biology and Pharmacology.
0022-3913/78/0239-0173500,60/0 9 1978 The C. V. Mosby Go.
sky4 suggested that sodium fluoride applied to dentin forms an effective surface barrier and results in desensitization of dentin. He described his methods of application but gave no experimental details or quantitative results. H o y t and B i b b y 6 used the paste suggested by Lukomsky which contained equal parts of sodium fluoride, clay, and glycerin; desensitization occurred in approximately 80% of the treatments. Their study did not include Controls and they did not adequately describe their method of evaluation. Other fluoride salts have been reported to be effective in reducing dentin hypersensitivity when applied as a dentifrice or as a topical agent.~-a~ Studies have indicated that various sources of fluoride have some degree of efficacy. Many patients in clinics of the Medical College of Georgia, School of Dentistry, have received treatment with the 33.3% sodium fluoride paste a n d / o r have used fluoride-containing dentifrices. Other patients have used a strontium chloride dentifrice that has been reported to be effective in desensitization? 1 since some of the patients have continued to complain of intolerable discomfort after treatment, a m e t h o d of assuring fluoride penetration into the dentinal tubules has been Suggested as a means of enhancing desensitization of dentin. Iontophoresis. Iontophoresis is a simple, welldocumented method of assuring penetration of charged drugs into surface tissues. When a direct current passes through an electrolyte positive ions travel toward th e negative electrode (the cathode) and negative ions travel toward the positi-ce electrode (the anode). T h e term iontophoresis is used in the health sciences to indicate the transfer of ions under electrical pressure into the body surface for therapeutic purposes. Although it has not been employed widely iontophoresis is a method of choice for administering
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pilocarpine for diagnosis of cystic fibrosis? 2 It is used to administer lidocaine and epinephrine for external ear canal anesthesia 13 and has also been used to administer vasodilators in the treatment of peripheral vascular disease? 4 Harris is has reviewed other uses of iontophoresis in medicine. Cocaine iontophoresis of the dental pulp was reported in 1896.16 In 1931 Grossman 17 reported that sterilization of root canals could be facilitated by electrolysis. Siemon is and Manning 19 were responsible for popularizing fluoride iontophoresis for dentin desensitization in the United States. Several other investigators have reported on fluoride iontophoresis. 2~ Gangarosa 27 recently reported that loose deciduous teeth can be extracted through iontophoretic application of local anesthetics and epinephrine into the oral mucosa, which results in a deep and profound topical anesthesia. Gangarosa and co-workers 2s-3~reported increased penetration of the antiviral drugs idoxuridine and Ara-AMP (9-B-D-Arabinofuranosyladenine 5 ' - M o n o p h o s phate) into mouse skin or rabbit eyes when applied by iontophoresis compared to topically. Also Gangarosa and associates 31 reported that idoxuridine iontophoresis was effective in treating h u m a n herpes orolabialis. Iontophoresis of fluoride. Siemon is and Manning 19 described the use of battery-operated devices* to apply current to teeth and a brush electrode to aid fluoride penetration into dentin; the indifferent (return) electrode was hand-held. Siemon is claimed 85% effectiveness but his data were based on only several patients. Manning '9 claimed that his method was effective in eliminating pain from cold-air blasts on exposed cervical dentin, but his report presented no data. Collins ~~ noted that chair-side desensitization had 0nly a transient effect and that home supplementation by means of an Ion toothbrusht was required to eliminate or reduce sensitivity. His study was double-blind in that control patients also received toothbrushes, but the batteries had been removed. Collins reported an 85% reduction in dentin sensitivity of the experimental group hut only about a 20% reduction for the control group. Lefkowitz ~1 and Lefkowitz and associates ~ were interested in pulp response and the mechanism of desensitization following iontophoresis of sound human teeth *Chayes Dental Instrument Corp., Danbury, Conn.; Lemos Co., Miami, Fla. "i'The Ion Co., Los Angeles, Calif.
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that had been indicated for extraction for prosthetic reasons. After they prepared Class V cavities having remaining dentin 1.2 m m thick the experimenters applied the negative electrode into the cavity using either sodium fluoride or the patient's saliva as the electrolyte. They claimed that the current induced formation of reparative dentin without causing. permanent pulpal damage whether sodium fluoride or saliva was applied. In the report by Jensen23 on the Ion toothbrush, which was in agreement with the findings of Collins, z~ the experimental group showed at least a 75% reduction in sensitivity while 10% was the highest reduction in control patients. Eshleman and Leonard 24 reviewed the literature and described their clinical observations of 32 patients who used the method of Siemon. 18 They claimed that there was immediate, long-term (12 to 19 months), and extremely effective reduction of sensitivity. No data were presented and no controls were described. Scott ~5 also presented a review of the literature on fluoride iontophoresis and attempted to determine whether the current can damage the odontoblasts. He applied current to freshly cut dentin and concluded that 1 milliampere of electricity applied for 1 minute (1 ma-min) caused no permanent injury. He claimed that desensitization occurred without lowering pulp vitality when this limit was observed. Shaeffer and associates 26 used an iontophoretic toothbrush and a stannous fluoride dentifrice. T h e y claimed that all patients who received electrical current with or without fluoride experienced desensitization. However, the toothbrush that they used delivered a positive charge to the tooth and such a charge opposes the penetration of fluoride. Murthy and associates 1 used a sable-brush applicator attached to a direct-current source for the iontophoresis of sodium fluoride and of saliva. Topical treatment with 33.3% sodium fluoride was also evaluated. This excellent study reported on an adequate number of subjects and used a doubleblind procedure, the correct negative charge and the appropriate, subjective evaluation. The authors concluded that the desensitization was immediate in most patients and that sodium fluoride iontophoresis provided the most effective treatment. Minkov and associates 2 also used an adequate number of subjects and appropriate evaluation procedures, but they concluded that 2% sodium fluoride applied topically with or without current
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was effective in desensitizing dentin. However, like Shaeffer and associates, 26 they used a positive electrode on the tooth. Many studies recommend the fluoride treatment for desensitization. Since iontophoresis assists penetration of ions into tissues there is a rational basis to using an electrical current to carry fluoride into the tooth, is M a n y clinical observations indicate the effectiveness of fluoride iontophoresis, but only a few studies have been adequately c o n t r o l l e d . 2~ ~ Two studies that did not demonstrate the effectiveness of fluoride iontophoresis used the wrong polarity on the tooth electrode z, zr; one claimed the current alone was effective 2 and the Other claimed that the fluoride was effective with or without current. 26 Mechanism of fluoride iontophoresis. Although the exact mechanism by which fluoride iontophoresis produces desensitization of dentin is not known, several hypotheses have been proposed. One mechanism proposed by Lefkowitz 21 and Lefkowitz a n d associates 22 involves the formation of reparative dentin following application of current to dentin, which results in dead tracts in the primary dentin. The dead tracts inhibit the passage of stimuli from the exposed dentin to the pulp. Walton and associates ~2 applied 2% sodium fluoride or sodium chloride to exlbosed dentin in dogs by cathodal iontophoresis at 1 or 5 ma-min. They reported no changes in the architecture of the odontoblasts after 7 or 56 days. This finding was in agreement with that of Lefkowitz. 21 However, there was no evidence of formation of secondary or reparative dentin in the dog after 56 days. There is a need for further research on this mechanism since the results in dogs were different than those in man. A second possible explanation of iontophoresis is that the electrical current produces paresthesia by altering the sensory mechanisms of pain conduction. We have found that 5 to 15/tamp or more of direct current blocks conduction in the isolated frog nerve. 33It seems reasonable that the 300 to 500 pamp of current used in desensitization may block dentinal pain conduction if it is assumed that electrical conduction similar to that observed in nerves is involved in sensory perception. Since iontophoretic desensitization has a rather long duration one would have to postulate either that this paresthesia is longlived or that another mechanism having a long-term effect is also active. A third alternative explanation of iontophoretic desensitization is that the concentration of fluoride
THE JOURNAL OF PROSTHETIC DENTISTRY
Fig. 1. The direct-current source that was used to desensitize teeth. The anode (left) is connected to the patient's arm. The cathode (right) is used to drive fluoride into the teeth. ions in dentinal tubules may be increased due to the fluoride iontophoresis. This could cause microprecipitation of calcium fluoride that may act to block hydrodynamically mediated pain-inducing stimuli. 34 Ehrlich and associates 35 observed increased fluoride uptake in exposed root dentin and precipitations in peritubular dentin after one topical application of 2% sodium fluoride. Souder and Schoonover3~ demonstrated that fluoride and calcium will remineralize dentin; the increased fluoride penetration into dentinal tubules presumably caused by iontophoresis may cause calcium fluoride precipitation, which in turn may decrease fluid movement induced by stimuli. This review and discussion clearly indicate that the mechanism of fluoride desensitization is unknown. Perhaps it will be better understood when more is known about the mechanism of dentin sensitivity. CLINICAL RESULTS The purpose of our clinical trials was to determine whether the equipment and technique used for iontophoresis of local anesthetics into the oral mucosa ~7 are adaptable to use in the fluoride desensitization of dentin. Materials and methods. Each tooth to be desensitized was isolated with cotton rolls or a rubber dam, thus enabling the dentist to deliver a carefully controlled amount of current. The direct-current source* is seen in Fig. 1. It is a modification of an *Electro-Medicator,, Model A1, Medtherm Gorp., Huntsville, Ala.
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Table I. Clinical trials of dentin desensitization by iontophoresis No. o[ patients/ teeth
Electrode
3/3
Cathode(-)
More sensitive (100%)
5/5
Anode(+ )
2. Cervical dentin exposure 3. Inlay or crown preparations 4. After periodontal surgery
9/41 4/17 4/25
Cathode Cathode Cathode
5. Hypoplastic enamel 6. Occlusalwear
1/2 2/21
Cathode Cathode
Moderate reduction (80%) Good reduction (20%) Good reduction (100%) Good reduction (100%) Moderate reduction (36%) Good reduction (64%) Good reduction (100%) Good reduction (100%)
Trial
1% sodium chloride (cervical dentin exposure) 2% sodium fluoride: 1. Reverse polarity (cervical dentin exposure)
Immediate effect on sensitivity*
*For long-term results see text.
apparatus used in a previously reported investigationY A flexible electrode was attached through a wire lead to the negative pole of the current source. A disposable plastic cotton holder made of Tygon tubing of appropriate diameter was placed over the electrode tip and a large pledget of absorbent cotton was inserted into the holder. The cotton was dampened with 2% sodium fluoride solution and applied to a tooth. The return or indifferent electrode was a conducting plastic disk assembled with a disk of blotting paper and a retaining ring; this electrode was strapped to the volar surface of the forearm. The blotting paper was saturated with 1% sodium nitrate or sodium chloride solution to facilitate the current flow. The current was adjusted to the patient's threshold, between 0.4 and 1 ma-min, and then reduced slightly. The patients did not feel any discomfort; they reported a slight tingling sensation which was eliminated by adjustment of the current. The maximum permissible dosage to one tooth did not exceed 1 ma-minY This dosage, recommended as safe by Scott, 25 is calculated by multiplying milliamperes used by the time in minutes. If some of the current flows into soft tissue it is difficult to measure the amount of current passing through the tooth. It is a safe assumption that the current delivered to the tooth will be no more than the relative ratio (area of electrode contacting the tooth/total area of electrode contact). To demonstrate this, if the electrode is 50% on tooth surfaces and 50% on soft tissue, less than half of the current will enter the tooth; therefore the amount of current must be doubled. Twenty-eight patients with 114 hypersensitive teeth were treated by iontophoresis with this system. All trials were not blind so that the technique could
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be evaluated. The type of trial and the number of patients in each group are shown in Table I. Sensitivity was evaluated through the use of an air blast. Before treatment patients could barely tolerate a minimal flow of air from the dental air syringe and a slight blast induced a definite transient pain and an attempt to withdraw from the stimulus. A good reduction in sensitivity was reported when, after the fluoride iontophoresis, the patient could tolerate unlimited air blasts without pain or reflex response for the entire period of the study. Moderate reduction indicates that the patient could tolerate high levels of air current with lessened pain or discomfort or that there was some return of sensitivity at the follow-up examination. No reduction indicated that there was little or no change in the amount of the air blast that the patient could tolerate. Follow-up examinations were made at 3 months to 3 years, depending upon when the patient entered the study. RESULTS The results are summarized in Table I. Increased sensitivity was found when sodium chloride was the electrolyte and the negative electrode was applied to the tooth. This was noted when we attempted to develop the sodium chloride iontophoresis as an electrical control; the procedure was not repeated further because it was extremely distressing to the patients. Under a positive electrode 2% sodium fluoride provided a moderate reduction of sensitivity in four out of five teeth, while in one tooth it provided a good reduction. The results obtained on dentin sensitivity caused by exposed cervical dentin, cavity preparation, hypoplastic enamel, or occlusal wear were dramatic when fluoride iontophoresis was used under the proper negative electrode. There was
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immediate relief of long duration. Reduced sensitivity lasted for the duration of the experiment, which was at least 3 months and up to 3 years for ten of the patients. In trials on root dentin exposed following periodontal surgery which also used negative fluoride iontophoresis, there was good reduction in 64% of the trials and moderate reduction in 36%. In nine teeth in which sensitivity reduction was rated as moderate following periodontal surgery, retreatment was required for three teeth after 6 weeks and six teeth after 1 year. The other 16 teeth in that group did not require any retreatment for the duration of the experiment. There were no apparent adverse effects of the procedure; the teeth remained healthy and asymptomatic as long as the patients were under observation. DISCUSSION The results of the clinical trials demonstrate that the iontophoretic technique used to administer local anesthetics to the oral mucosa is adaptable to fluoride iontophoresis for dentin desensitization? z When iontophoresis of fluoride was performed with the cathode on the tooth the treatment was clinically effective. These clinical trials agree with the results reported by M u r t h y and associates? However, Minkov and associates ~ reported that iontophoresis was no more effective than topical application when fluoride was applied to the tooth under an anode. Because an anode is positive it tends to resist the penetration of fluoride into the tooth. Minkov and associates z noted that their results were similar to those of Schaeffer and associates, 26 who claimed that the benefits of iontophoresis are due to the current and not to the fluoride application. The toothbrush used by Sehaeffer and associates 26 contained a wet cell and magnesium at the tooth bristles, while tin was the indifferent electrode. The following reactions would be expected in such a cell: Mg ~ ++ + 2(e) E M F = +2.3750 Sn~ ++ + 2(e) E M F = +0.1364 Thus physiochemieal law dictates that magnesium is more positive with respect to tin; magnesium would act as the anode. 3s The polarity used by Schaeffer and associates was the same as that used by Minkov and associates. 2 Both groups applied fluoride under a positive electrode, which would explain the similarity of results obtained. We too obtained a modest reduction in sensitivity using sodium fluoride under a positive electrode; this effect is probably due to (I) a topical effect of fluoride, (2) a nonspecific effect of current, or (3) electro-osmosis, a process that
THE JOURNAL OF PROSTHETIC DENTISTRY
causes water and dissolved solutes to enter tissues due to the transfer of charged ions. '5 O u r results indicate that fluoride iontophoresis is effective in the treatment of all types of dentin hypersensitivity. However, Sensitivity of dentin exposed after periodontal surgery was somewhat resistant to iontophoresis. Some teeth with massive dentin exposure showed only moderate reduction. This reduced effectiveness seems to be related to poor adaptation of our electrodes to the inaccessible dentin, e.g., exposed interproximal dentin. CONCLUSION A review of the literature on treatment of dentin hypersensitivity by use of fluorides and fluoride iontophoresis was presented. It was concluded that topical applications of fluoride are modestly effective for treatment of dentin hypersensitivity, but the most rapid and effective relief follows fluoride iontophoresis. This technique has a broad application in dental practice since fluoride iontophoresis was shown to be an effective desensitizer in cavity preparation, before cementation of restorations, and in cases of occlusal wear and enamel hypoplasia. The report also presents a new and effective method for the iontophoresis of fluoride for dentin desensitization. We thank Drs. R. Walton, J. Garnick, and D. Pashley for their excellent advice and the Medtherm Corp. for supplying the Electro-Medieator and accessories.
REFERENCES 1. Murthy, K. S., Talim, S. T., and Singh, I.: A comparative evaluation of topical application and iontophoresis of sodium fluoride for desensitization of hypersensitive dentin. Oral Surg 36:448, 1973. 2. Minkov, B., Marmari, I., Gedalia, I., and Garfunkel, A.: The effectiveness of sodium fluoride treatment with and without iontophoresis on the reduction of hypersensitive dentin. J Periodontol 46:246, 1975. 3. Grossman, L,: A systematic method for the treatment of hypersensitive dentin. J Am Dent Assoc 22:592, 1935. 4. Lukomsky, E. H.: Fluorine therapy for exposed dentin and alveolar atrophy. J Dent Res 20:649, 1941. 5. Hoyt, W. H., and Bibby, B. G.: Use of sodium fluoride for desensitizing dentin. J Am Dent Assoc 30:1372, 1943. 6. Hazen, S., Volpe, A., and King, W.: Comparative desensitizing effect of dentifrice containing sodium monofluorophosphate, stannous fluoride, and formalin. Periodontics 6:230, 1968. 7. Bolden, T. E., Volpe, A. R., and King, W. J.: The desensitizing effect of a sodium monofluorophosphate dentifrice. Periodontics 6:112, 1968. 8. Kanause, M., and Ash, M.: Effect of sodium monofluorophosphate dentifrice on teeth sensitive to both hot and cold stimuli. J Periodontol 40:38, 1969.
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9.
10.
11.
12.
13.
14.
15.
16.
17. 18.
19. 20. 21. 22.
23.
24.
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Shapiro, W. B., Kaslick, R. S., Chasens, A. I., and Weinstein, D.: Controlled clinical comparison between a strontium chloride and a sodium monofluorophosphate tooth paste in diminishing root hypersensitivity. J Periodontol 41:523, 1970. Bhatia, H. L.: Use of sodium silicofluoride as a desensitizing agent for exposed sensitive cementum and cervical dentin. Cited by Murthy, K. S., Talim, S. T., and Singh, I.: A comparative evaluation of topical application and iontophoresis of sodium fluoride for desensitization of hypersensitive dentin. Oral Surg 36:448, 1973. Meffert, R. M., and Hoskins, S. W.: Effect of a strontium chloride dentifrice in relieving dental hypersensitivity. J Periodontol 35:232, 1964. Gibson, L. W., and Cooke, R. E.: A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics 23:545, 1959. Comeau, M., Brummett, R., and Vernon, J.: Local anesthesia of ear by iontophoresis. Arch Otolaryngol 98:114, 1973. Stone, T. W.: Responses of blood vessels to various amines applied by microniontophoresis. J Pharm Pharmacol 24:318, 1972. Harris, R.: Iontophoresis. In Licht, S. (editor): Therapeutic Electricity and Ultra-Violet Radiation, ed 2. New Haven, 1967, E. Licht (Publisher), pp 156-178. Morton, W. J.: Guaiacol-cocaine cataphoresis and local anesthesia; a new cataphoric electrode and the Wheeler fractional volt selector. Dent Cosmos 38:48, 1896. Grossman, L. W.: Experimental and applied studies in electrosterilization. Dent Cosmos 73:147, 1931. Siemon, W. H.: A new approach in solving the problem of hypersensitivity and postoperative distress in dentin and cementum. J Conn State Dent Assoc 34:5, 1960. Manning, M. W.: New approach to desensitization of cervical dentin. Dent Survey 37:731, 1961. Collins, E. M.: Desensitization of hypersensitive teeth. Dent Dig 68:360, 1962. Lefkowitz, W.: Pulp response to ionization. J PROSTHET DE~rr 12:966, 1960. Lefkowitz, W., Burdick, H. D., and Moore, D. L.: Desensitization of dentin by bioelectric induction of secondary dentin. J PROSTHETDENT 13:940, 1963. Jensen, A. L.: Hypersensitivity controlled by iontophoresis: Double-blind clinical investigation. J Am Dent Assoc 68:216, 1964. Eshleman, J. R., and Leonard, E. D., Jr.: Desensitization of dentin by iontophoresis; A review and case reports: Clinical impression. J Oral Therapy Pharmacol 1:526, 1965.
25. 26.
27. 28.
29.
30.
31.
32.
33. 34.
35.
36. 37.
38.
Scott, H. M., Jr.: Reduction of sensitivity by eleetrophoresis. J Dent Child 29:225, 1962. Schaeffer, M. L., Bixler, D., and Yu, P.-L.: The effectiveness of iontophoresis in reducing cervical hypersensitivity. J Periodontol 42:695, 1971. Gangarosa, L. P., Sr.: Iontophoresis for surface local anesthesia. J Am Dent Assoc 88:125, 1974. Gangarosa, L. P., Park, N. H., and Hill, J. M.: Inhibition of thymidine (TdR) incorporation into DNA after idoxuridine (IDU) iontophoresis. J Dent Res 55:B146, 1976. (Abst No. 337) Park, N. H., Gangarosa, L. P., and Hilt, J. M.: Iontophoresis of idoxuridine into neonatal mouse skin: Pharmacokinetic and biochemical studies. J Dent Res 55:B146, 1976. (Abst No. 338) Hill, J. M,, Gangarosa, L. P., and Park, N. H.: Iontophoretie application of antiviral chemotherapeutic agents. In New York Academy of Sciences: Third Conference on Antiviral Substances. Ann N Y Acad Sci 284:604, 1977. Gangarosa, L. P., Merchant, H. W., Park, N. H., and Hill, J. M.: Iontophoretic application of id0xuridine in recurrent herpes labialis: Report of 18 clinical trials. J Dent Res 56:B194, 1977. (Abst No. 569) Walton, R., Gangarosa, L., Leonard, L., and Sharawy, R.: Pulp and dentin response to iontophoresis of NaF on exposed roots. J Dent Res 55:B228, 1976. (Abst No. 667) Gangarosa, L. P, and Park, N. H.: Effect of iontophoresis on frog sciatic nerve conduction. (Unpublished data) Briinnstr6m, M., Johnson, G., and Linden, L.: Fluid flow and pain response in the dentin produced by hydrostatic pressure. Odontol Revy 20:15, 1969. Ehrlich, J., Hochman, N., Gedalia, I., and Tal, M.: Residual fluoride concentrations and scanning electron microscopic olamination of root surfaces of human teeth after topical application of fluoride in vivo. J Dent Res 54:897, 1975. Souder, W., and Schoonover, I. C.: Experimental remineralization of dentin. J Am Dent Assoe 3h1579, 1944. Gangarosa, L. P. (editor): Operating Instructions for Dental Application of Electro-Medieator Model AE 1. Huntsville, Ala., 1975, MedTherm Corp. Kanai, M., Kamori, H., and Hirano, H.: Physieo-chemical Science Institute: Tokyo Dental College, Report to XII Federation Dentaire Dental Congress, Rome, 1957.
Reprint requests to: DR. L. P. GANGAROSA MEDICAL COLLEGE OF GEORGIA SCHOOL OF DENTISTRY AUGUSTA, GA. 30902
FEBRUARY 1978
VOLUME39
NUMBER2
Two recent research reports have expressed a difference of opinion on the merit of desensitizing hypersensitive dentin by fluoride iontophoresis. I n 1973 Murthy and associates 1 reported on a doubleblind controlled study comparing the effectiveness of 1% sodium fluoride iontophoresis with the effectiveness of saliva iontophoresis and of the topical application of 33.3% sodium fluoride paste. The authors concluded that the application of fluoride ions under a negative electrode was the most effective means of dentin desensitization. More recently Minkov and associates 2 reported a significant decrease in the sensitivity of exposed cervical "dentin after twelve treatments over a 6 week period using a 2% sodium fluoride solution; the decrease occurred whether the solution was applied topically without current or under a positive electrode. Those dissenting articles induced us to review the literature on fluoride desensitization and describe an effective clinical method of attaining dentin desensitization by iontophoresis. LITERATURE REVIEW
The ideal dentin desensitizer. Grossman 3 suggested that the ideal desensitizer: (I) should not be undulyirritating to the pulp, (2)should be relatively painless, (3) should be easy to apply, (4) should be permanently effective, (5) should act quickly, (6) should be consistently effective, and (7) should not cause tooth discoloration. The agents currently in use should be evaluated according to these criteria; of the methods currently or previously in vogue none has fulfilled the ideal, but fluoride therapy appears to be the most promising method. Topical application of fluoride. In 1941 Lukom*Professor and Goordinator of Pharmacology, Departments of Oral Biology and Pharmacology. **Postdoctoral Fellow, Departments of Oral Biology and Pharmacology.
0022-3913/78/0239-0173500,60/0 9 1978 The C. V. Mosby Go.
sky4 suggested that sodium fluoride applied to dentin forms an effective surface barrier and results in desensitization of dentin. He described his methods of application but gave no experimental details or quantitative results. H o y t and B i b b y 6 used the paste suggested by Lukomsky which contained equal parts of sodium fluoride, clay, and glycerin; desensitization occurred in approximately 80% of the treatments. Their study did not include Controls and they did not adequately describe their method of evaluation. Other fluoride salts have been reported to be effective in reducing dentin hypersensitivity when applied as a dentifrice or as a topical agent.~-a~ Studies have indicated that various sources of fluoride have some degree of efficacy. Many patients in clinics of the Medical College of Georgia, School of Dentistry, have received treatment with the 33.3% sodium fluoride paste a n d / o r have used fluoride-containing dentifrices. Other patients have used a strontium chloride dentifrice that has been reported to be effective in desensitization? 1 since some of the patients have continued to complain of intolerable discomfort after treatment, a m e t h o d of assuring fluoride penetration into the dentinal tubules has been Suggested as a means of enhancing desensitization of dentin. Iontophoresis. Iontophoresis is a simple, welldocumented method of assuring penetration of charged drugs into surface tissues. When a direct current passes through an electrolyte positive ions travel toward th e negative electrode (the cathode) and negative ions travel toward the positi-ce electrode (the anode). T h e term iontophoresis is used in the health sciences to indicate the transfer of ions under electrical pressure into the body surface for therapeutic purposes. Although it has not been employed widely iontophoresis is a method of choice for administering
THE IOURNAL OF PROSTHETIC DENTISTRY 173
GANGAROSA AND PARK
pilocarpine for diagnosis of cystic fibrosis? 2 It is used to administer lidocaine and epinephrine for external ear canal anesthesia 13 and has also been used to administer vasodilators in the treatment of peripheral vascular disease? 4 Harris is has reviewed other uses of iontophoresis in medicine. Cocaine iontophoresis of the dental pulp was reported in 1896.16 In 1931 Grossman 17 reported that sterilization of root canals could be facilitated by electrolysis. Siemon is and Manning 19 were responsible for popularizing fluoride iontophoresis for dentin desensitization in the United States. Several other investigators have reported on fluoride iontophoresis. 2~ Gangarosa 27 recently reported that loose deciduous teeth can be extracted through iontophoretic application of local anesthetics and epinephrine into the oral mucosa, which results in a deep and profound topical anesthesia. Gangarosa and co-workers 2s-3~reported increased penetration of the antiviral drugs idoxuridine and Ara-AMP (9-B-D-Arabinofuranosyladenine 5 ' - M o n o p h o s phate) into mouse skin or rabbit eyes when applied by iontophoresis compared to topically. Also Gangarosa and associates 31 reported that idoxuridine iontophoresis was effective in treating h u m a n herpes orolabialis. Iontophoresis of fluoride. Siemon is and Manning 19 described the use of battery-operated devices* to apply current to teeth and a brush electrode to aid fluoride penetration into dentin; the indifferent (return) electrode was hand-held. Siemon is claimed 85% effectiveness but his data were based on only several patients. Manning '9 claimed that his method was effective in eliminating pain from cold-air blasts on exposed cervical dentin, but his report presented no data. Collins ~~ noted that chair-side desensitization had 0nly a transient effect and that home supplementation by means of an Ion toothbrusht was required to eliminate or reduce sensitivity. His study was double-blind in that control patients also received toothbrushes, but the batteries had been removed. Collins reported an 85% reduction in dentin sensitivity of the experimental group hut only about a 20% reduction for the control group. Lefkowitz ~1 and Lefkowitz and associates ~ were interested in pulp response and the mechanism of desensitization following iontophoresis of sound human teeth *Chayes Dental Instrument Corp., Danbury, Conn.; Lemos Co., Miami, Fla. "i'The Ion Co., Los Angeles, Calif.
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that had been indicated for extraction for prosthetic reasons. After they prepared Class V cavities having remaining dentin 1.2 m m thick the experimenters applied the negative electrode into the cavity using either sodium fluoride or the patient's saliva as the electrolyte. They claimed that the current induced formation of reparative dentin without causing. permanent pulpal damage whether sodium fluoride or saliva was applied. In the report by Jensen23 on the Ion toothbrush, which was in agreement with the findings of Collins, z~ the experimental group showed at least a 75% reduction in sensitivity while 10% was the highest reduction in control patients. Eshleman and Leonard 24 reviewed the literature and described their clinical observations of 32 patients who used the method of Siemon. 18 They claimed that there was immediate, long-term (12 to 19 months), and extremely effective reduction of sensitivity. No data were presented and no controls were described. Scott ~5 also presented a review of the literature on fluoride iontophoresis and attempted to determine whether the current can damage the odontoblasts. He applied current to freshly cut dentin and concluded that 1 milliampere of electricity applied for 1 minute (1 ma-min) caused no permanent injury. He claimed that desensitization occurred without lowering pulp vitality when this limit was observed. Shaeffer and associates 26 used an iontophoretic toothbrush and a stannous fluoride dentifrice. T h e y claimed that all patients who received electrical current with or without fluoride experienced desensitization. However, the toothbrush that they used delivered a positive charge to the tooth and such a charge opposes the penetration of fluoride. Murthy and associates 1 used a sable-brush applicator attached to a direct-current source for the iontophoresis of sodium fluoride and of saliva. Topical treatment with 33.3% sodium fluoride was also evaluated. This excellent study reported on an adequate number of subjects and used a doubleblind procedure, the correct negative charge and the appropriate, subjective evaluation. The authors concluded that the desensitization was immediate in most patients and that sodium fluoride iontophoresis provided the most effective treatment. Minkov and associates 2 also used an adequate number of subjects and appropriate evaluation procedures, but they concluded that 2% sodium fluoride applied topically with or without current
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was effective in desensitizing dentin. However, like Shaeffer and associates, 26 they used a positive electrode on the tooth. Many studies recommend the fluoride treatment for desensitization. Since iontophoresis assists penetration of ions into tissues there is a rational basis to using an electrical current to carry fluoride into the tooth, is M a n y clinical observations indicate the effectiveness of fluoride iontophoresis, but only a few studies have been adequately c o n t r o l l e d . 2~ ~ Two studies that did not demonstrate the effectiveness of fluoride iontophoresis used the wrong polarity on the tooth electrode z, zr; one claimed the current alone was effective 2 and the Other claimed that the fluoride was effective with or without current. 26 Mechanism of fluoride iontophoresis. Although the exact mechanism by which fluoride iontophoresis produces desensitization of dentin is not known, several hypotheses have been proposed. One mechanism proposed by Lefkowitz 21 and Lefkowitz a n d associates 22 involves the formation of reparative dentin following application of current to dentin, which results in dead tracts in the primary dentin. The dead tracts inhibit the passage of stimuli from the exposed dentin to the pulp. Walton and associates ~2 applied 2% sodium fluoride or sodium chloride to exlbosed dentin in dogs by cathodal iontophoresis at 1 or 5 ma-min. They reported no changes in the architecture of the odontoblasts after 7 or 56 days. This finding was in agreement with that of Lefkowitz. 21 However, there was no evidence of formation of secondary or reparative dentin in the dog after 56 days. There is a need for further research on this mechanism since the results in dogs were different than those in man. A second possible explanation of iontophoresis is that the electrical current produces paresthesia by altering the sensory mechanisms of pain conduction. We have found that 5 to 15/tamp or more of direct current blocks conduction in the isolated frog nerve. 33It seems reasonable that the 300 to 500 pamp of current used in desensitization may block dentinal pain conduction if it is assumed that electrical conduction similar to that observed in nerves is involved in sensory perception. Since iontophoretic desensitization has a rather long duration one would have to postulate either that this paresthesia is longlived or that another mechanism having a long-term effect is also active. A third alternative explanation of iontophoretic desensitization is that the concentration of fluoride
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Fig. 1. The direct-current source that was used to desensitize teeth. The anode (left) is connected to the patient's arm. The cathode (right) is used to drive fluoride into the teeth. ions in dentinal tubules may be increased due to the fluoride iontophoresis. This could cause microprecipitation of calcium fluoride that may act to block hydrodynamically mediated pain-inducing stimuli. 34 Ehrlich and associates 35 observed increased fluoride uptake in exposed root dentin and precipitations in peritubular dentin after one topical application of 2% sodium fluoride. Souder and Schoonover3~ demonstrated that fluoride and calcium will remineralize dentin; the increased fluoride penetration into dentinal tubules presumably caused by iontophoresis may cause calcium fluoride precipitation, which in turn may decrease fluid movement induced by stimuli. This review and discussion clearly indicate that the mechanism of fluoride desensitization is unknown. Perhaps it will be better understood when more is known about the mechanism of dentin sensitivity. CLINICAL RESULTS The purpose of our clinical trials was to determine whether the equipment and technique used for iontophoresis of local anesthetics into the oral mucosa ~7 are adaptable to use in the fluoride desensitization of dentin. Materials and methods. Each tooth to be desensitized was isolated with cotton rolls or a rubber dam, thus enabling the dentist to deliver a carefully controlled amount of current. The direct-current source* is seen in Fig. 1. It is a modification of an *Electro-Medicator,, Model A1, Medtherm Gorp., Huntsville, Ala.
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Table I. Clinical trials of dentin desensitization by iontophoresis No. o[ patients/ teeth
Electrode
3/3
Cathode(-)
More sensitive (100%)
5/5
Anode(+ )
2. Cervical dentin exposure 3. Inlay or crown preparations 4. After periodontal surgery
9/41 4/17 4/25
Cathode Cathode Cathode
5. Hypoplastic enamel 6. Occlusalwear
1/2 2/21
Cathode Cathode
Moderate reduction (80%) Good reduction (20%) Good reduction (100%) Good reduction (100%) Moderate reduction (36%) Good reduction (64%) Good reduction (100%) Good reduction (100%)
Trial
1% sodium chloride (cervical dentin exposure) 2% sodium fluoride: 1. Reverse polarity (cervical dentin exposure)
Immediate effect on sensitivity*
*For long-term results see text.
apparatus used in a previously reported investigationY A flexible electrode was attached through a wire lead to the negative pole of the current source. A disposable plastic cotton holder made of Tygon tubing of appropriate diameter was placed over the electrode tip and a large pledget of absorbent cotton was inserted into the holder. The cotton was dampened with 2% sodium fluoride solution and applied to a tooth. The return or indifferent electrode was a conducting plastic disk assembled with a disk of blotting paper and a retaining ring; this electrode was strapped to the volar surface of the forearm. The blotting paper was saturated with 1% sodium nitrate or sodium chloride solution to facilitate the current flow. The current was adjusted to the patient's threshold, between 0.4 and 1 ma-min, and then reduced slightly. The patients did not feel any discomfort; they reported a slight tingling sensation which was eliminated by adjustment of the current. The maximum permissible dosage to one tooth did not exceed 1 ma-minY This dosage, recommended as safe by Scott, 25 is calculated by multiplying milliamperes used by the time in minutes. If some of the current flows into soft tissue it is difficult to measure the amount of current passing through the tooth. It is a safe assumption that the current delivered to the tooth will be no more than the relative ratio (area of electrode contacting the tooth/total area of electrode contact). To demonstrate this, if the electrode is 50% on tooth surfaces and 50% on soft tissue, less than half of the current will enter the tooth; therefore the amount of current must be doubled. Twenty-eight patients with 114 hypersensitive teeth were treated by iontophoresis with this system. All trials were not blind so that the technique could
I76
be evaluated. The type of trial and the number of patients in each group are shown in Table I. Sensitivity was evaluated through the use of an air blast. Before treatment patients could barely tolerate a minimal flow of air from the dental air syringe and a slight blast induced a definite transient pain and an attempt to withdraw from the stimulus. A good reduction in sensitivity was reported when, after the fluoride iontophoresis, the patient could tolerate unlimited air blasts without pain or reflex response for the entire period of the study. Moderate reduction indicates that the patient could tolerate high levels of air current with lessened pain or discomfort or that there was some return of sensitivity at the follow-up examination. No reduction indicated that there was little or no change in the amount of the air blast that the patient could tolerate. Follow-up examinations were made at 3 months to 3 years, depending upon when the patient entered the study. RESULTS The results are summarized in Table I. Increased sensitivity was found when sodium chloride was the electrolyte and the negative electrode was applied to the tooth. This was noted when we attempted to develop the sodium chloride iontophoresis as an electrical control; the procedure was not repeated further because it was extremely distressing to the patients. Under a positive electrode 2% sodium fluoride provided a moderate reduction of sensitivity in four out of five teeth, while in one tooth it provided a good reduction. The results obtained on dentin sensitivity caused by exposed cervical dentin, cavity preparation, hypoplastic enamel, or occlusal wear were dramatic when fluoride iontophoresis was used under the proper negative electrode. There was
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immediate relief of long duration. Reduced sensitivity lasted for the duration of the experiment, which was at least 3 months and up to 3 years for ten of the patients. In trials on root dentin exposed following periodontal surgery which also used negative fluoride iontophoresis, there was good reduction in 64% of the trials and moderate reduction in 36%. In nine teeth in which sensitivity reduction was rated as moderate following periodontal surgery, retreatment was required for three teeth after 6 weeks and six teeth after 1 year. The other 16 teeth in that group did not require any retreatment for the duration of the experiment. There were no apparent adverse effects of the procedure; the teeth remained healthy and asymptomatic as long as the patients were under observation. DISCUSSION The results of the clinical trials demonstrate that the iontophoretic technique used to administer local anesthetics to the oral mucosa is adaptable to fluoride iontophoresis for dentin desensitization? z When iontophoresis of fluoride was performed with the cathode on the tooth the treatment was clinically effective. These clinical trials agree with the results reported by M u r t h y and associates? However, Minkov and associates ~ reported that iontophoresis was no more effective than topical application when fluoride was applied to the tooth under an anode. Because an anode is positive it tends to resist the penetration of fluoride into the tooth. Minkov and associates z noted that their results were similar to those of Schaeffer and associates, 26 who claimed that the benefits of iontophoresis are due to the current and not to the fluoride application. The toothbrush used by Sehaeffer and associates 26 contained a wet cell and magnesium at the tooth bristles, while tin was the indifferent electrode. The following reactions would be expected in such a cell: Mg ~ ++ + 2(e) E M F = +2.3750 Sn~ ++ + 2(e) E M F = +0.1364 Thus physiochemieal law dictates that magnesium is more positive with respect to tin; magnesium would act as the anode. 3s The polarity used by Schaeffer and associates was the same as that used by Minkov and associates. 2 Both groups applied fluoride under a positive electrode, which would explain the similarity of results obtained. We too obtained a modest reduction in sensitivity using sodium fluoride under a positive electrode; this effect is probably due to (I) a topical effect of fluoride, (2) a nonspecific effect of current, or (3) electro-osmosis, a process that
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causes water and dissolved solutes to enter tissues due to the transfer of charged ions. '5 O u r results indicate that fluoride iontophoresis is effective in the treatment of all types of dentin hypersensitivity. However, Sensitivity of dentin exposed after periodontal surgery was somewhat resistant to iontophoresis. Some teeth with massive dentin exposure showed only moderate reduction. This reduced effectiveness seems to be related to poor adaptation of our electrodes to the inaccessible dentin, e.g., exposed interproximal dentin. CONCLUSION A review of the literature on treatment of dentin hypersensitivity by use of fluorides and fluoride iontophoresis was presented. It was concluded that topical applications of fluoride are modestly effective for treatment of dentin hypersensitivity, but the most rapid and effective relief follows fluoride iontophoresis. This technique has a broad application in dental practice since fluoride iontophoresis was shown to be an effective desensitizer in cavity preparation, before cementation of restorations, and in cases of occlusal wear and enamel hypoplasia. The report also presents a new and effective method for the iontophoresis of fluoride for dentin desensitization. We thank Drs. R. Walton, J. Garnick, and D. Pashley for their excellent advice and the Medtherm Corp. for supplying the Electro-Medieator and accessories.
REFERENCES 1. Murthy, K. S., Talim, S. T., and Singh, I.: A comparative evaluation of topical application and iontophoresis of sodium fluoride for desensitization of hypersensitive dentin. Oral Surg 36:448, 1973. 2. Minkov, B., Marmari, I., Gedalia, I., and Garfunkel, A.: The effectiveness of sodium fluoride treatment with and without iontophoresis on the reduction of hypersensitive dentin. J Periodontol 46:246, 1975. 3. Grossman, L,: A systematic method for the treatment of hypersensitive dentin. J Am Dent Assoc 22:592, 1935. 4. Lukomsky, E. H.: Fluorine therapy for exposed dentin and alveolar atrophy. J Dent Res 20:649, 1941. 5. Hoyt, W. H., and Bibby, B. G.: Use of sodium fluoride for desensitizing dentin. J Am Dent Assoc 30:1372, 1943. 6. Hazen, S., Volpe, A., and King, W.: Comparative desensitizing effect of dentifrice containing sodium monofluorophosphate, stannous fluoride, and formalin. Periodontics 6:230, 1968. 7. Bolden, T. E., Volpe, A. R., and King, W. J.: The desensitizing effect of a sodium monofluorophosphate dentifrice. Periodontics 6:112, 1968. 8. Kanause, M., and Ash, M.: Effect of sodium monofluorophosphate dentifrice on teeth sensitive to both hot and cold stimuli. J Periodontol 40:38, 1969.
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9.
10.
11.
12.
13.
14.
15.
16.
17. 18.
19. 20. 21. 22.
23.
24.
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Shapiro, W. B., Kaslick, R. S., Chasens, A. I., and Weinstein, D.: Controlled clinical comparison between a strontium chloride and a sodium monofluorophosphate tooth paste in diminishing root hypersensitivity. J Periodontol 41:523, 1970. Bhatia, H. L.: Use of sodium silicofluoride as a desensitizing agent for exposed sensitive cementum and cervical dentin. Cited by Murthy, K. S., Talim, S. T., and Singh, I.: A comparative evaluation of topical application and iontophoresis of sodium fluoride for desensitization of hypersensitive dentin. Oral Surg 36:448, 1973. Meffert, R. M., and Hoskins, S. W.: Effect of a strontium chloride dentifrice in relieving dental hypersensitivity. J Periodontol 35:232, 1964. Gibson, L. W., and Cooke, R. E.: A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics 23:545, 1959. Comeau, M., Brummett, R., and Vernon, J.: Local anesthesia of ear by iontophoresis. Arch Otolaryngol 98:114, 1973. Stone, T. W.: Responses of blood vessels to various amines applied by microniontophoresis. J Pharm Pharmacol 24:318, 1972. Harris, R.: Iontophoresis. In Licht, S. (editor): Therapeutic Electricity and Ultra-Violet Radiation, ed 2. New Haven, 1967, E. Licht (Publisher), pp 156-178. Morton, W. J.: Guaiacol-cocaine cataphoresis and local anesthesia; a new cataphoric electrode and the Wheeler fractional volt selector. Dent Cosmos 38:48, 1896. Grossman, L. W.: Experimental and applied studies in electrosterilization. Dent Cosmos 73:147, 1931. Siemon, W. H.: A new approach in solving the problem of hypersensitivity and postoperative distress in dentin and cementum. J Conn State Dent Assoc 34:5, 1960. Manning, M. W.: New approach to desensitization of cervical dentin. Dent Survey 37:731, 1961. Collins, E. M.: Desensitization of hypersensitive teeth. Dent Dig 68:360, 1962. Lefkowitz, W.: Pulp response to ionization. J PROSTHET DE~rr 12:966, 1960. Lefkowitz, W., Burdick, H. D., and Moore, D. L.: Desensitization of dentin by bioelectric induction of secondary dentin. J PROSTHETDENT 13:940, 1963. Jensen, A. L.: Hypersensitivity controlled by iontophoresis: Double-blind clinical investigation. J Am Dent Assoc 68:216, 1964. Eshleman, J. R., and Leonard, E. D., Jr.: Desensitization of dentin by iontophoresis; A review and case reports: Clinical impression. J Oral Therapy Pharmacol 1:526, 1965.
25. 26.
27. 28.
29.
30.
31.
32.
33. 34.
35.
36. 37.
38.
Scott, H. M., Jr.: Reduction of sensitivity by eleetrophoresis. J Dent Child 29:225, 1962. Schaeffer, M. L., Bixler, D., and Yu, P.-L.: The effectiveness of iontophoresis in reducing cervical hypersensitivity. J Periodontol 42:695, 1971. Gangarosa, L. P., Sr.: Iontophoresis for surface local anesthesia. J Am Dent Assoc 88:125, 1974. Gangarosa, L. P., Park, N. H., and Hill, J. M.: Inhibition of thymidine (TdR) incorporation into DNA after idoxuridine (IDU) iontophoresis. J Dent Res 55:B146, 1976. (Abst No. 337) Park, N. H., Gangarosa, L. P., and Hilt, J. M.: Iontophoresis of idoxuridine into neonatal mouse skin: Pharmacokinetic and biochemical studies. J Dent Res 55:B146, 1976. (Abst No. 338) Hill, J. M,, Gangarosa, L. P., and Park, N. H.: Iontophoretie application of antiviral chemotherapeutic agents. In New York Academy of Sciences: Third Conference on Antiviral Substances. Ann N Y Acad Sci 284:604, 1977. Gangarosa, L. P., Merchant, H. W., Park, N. H., and Hill, J. M.: Iontophoretic application of id0xuridine in recurrent herpes labialis: Report of 18 clinical trials. J Dent Res 56:B194, 1977. (Abst No. 569) Walton, R., Gangarosa, L., Leonard, L., and Sharawy, R.: Pulp and dentin response to iontophoresis of NaF on exposed roots. J Dent Res 55:B228, 1976. (Abst No. 667) Gangarosa, L. P, and Park, N. H.: Effect of iontophoresis on frog sciatic nerve conduction. (Unpublished data) Briinnstr6m, M., Johnson, G., and Linden, L.: Fluid flow and pain response in the dentin produced by hydrostatic pressure. Odontol Revy 20:15, 1969. Ehrlich, J., Hochman, N., Gedalia, I., and Tal, M.: Residual fluoride concentrations and scanning electron microscopic olamination of root surfaces of human teeth after topical application of fluoride in vivo. J Dent Res 54:897, 1975. Souder, W., and Schoonover, I. C.: Experimental remineralization of dentin. J Am Dent Assoe 3h1579, 1944. Gangarosa, L. P. (editor): Operating Instructions for Dental Application of Electro-Medieator Model AE 1. Huntsville, Ala., 1975, MedTherm Corp. Kanai, M., Kamori, H., and Hirano, H.: Physieo-chemical Science Institute: Tokyo Dental College, Report to XII Federation Dentaire Dental Congress, Rome, 1957.
Reprint requests to: DR. L. P. GANGAROSA MEDICAL COLLEGE OF GEORGIA SCHOOL OF DENTISTRY AUGUSTA, GA. 30902
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VOLUME39
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