Intra-Oral Topical Anaesthetics- A Review

Review

Intra-oral topical anaesthetics: a reviewJ.G. Meechan*

Department of Oral and Maxillofacial Surgery, The Dental School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon TyneNE2 4BW, UK

Received 15 December 1998; received in revised form 1 February 1999; accepted 19 February 1999

Abstract

Objective: This review considers the use of topical anaesthetics in the mouth to reduce the discomfort of local anaesthetic injections andintra-oral operative procedures.

Data sources: Electronic literature search using Pub Med, manual search of references within papers found by the primary search andmanual searching of abstracts from scientific meetings.

Study selection: The articles selected for this review investigate or used topical anaesthesia in dental procedures.Conclusions: The use of topical anaesthetics does not guarantee pain-free dental local anaesthesia. Efficacy is dependent upon the duration

of application and the gauge of needle used. Evidence is available that the use of topical anaesthesia alone is sufficient to perform some intra-oral procedures including periodontal manipulations, operative dentistry and oral surgery. q 1999 Elsevier Science Ltd. All rights reserved.

Keywords: Topical anaesthetics; Intra-oral operations; Local anaesthesia

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32. Pharmacology of topical application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43. Studies into the efficacy of topical anaesthetics prior to needle penetration or local anaesthetic injections . . . . . . . . 7

3.1. Studies reporting positive results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73.2. Studies reporting negative results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

4. The use of topical anaesthetics to reduce the discomfort of potentially painful intra-oral procedures . . . . . . . . . . . . 94.1. Studies on use in the gingival crevice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94.2. Studies on use on gingiva . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94.3. Study into use of topical as sole anaesthetic for biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104.4. Studies into use of topical anaesthetics to provide dentinal/pulpal anaesthesia . . . . . . . . . . . . . . . . . . . . . . . . 104.5. Studies into the use of topical anaesthetics as sole means of anaesthesia for dental extractions . . . . . . . . . . . 104.6. Use of topical agents for post-extraction pain relief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

5. Plasma levels following topical anaesthetic application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116. Adverse effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

1. Introduction

Surface anaesthesia may be achieved by physical meth-ods, such as refrigeration anaesthesia, or by pharmacologi-cal means using topically active anaesthetic agents.

The ideal local anaesthetic agent should be active

when applied topically. However not all local anaes-thetics used in dental practice achieve this, some suchas procaine and mepivacaine cannot achieve a topical effectat clinically acceptable concentrations [1,2]. Effectiveadministration of a local anaesthetic without the need forinjection would be a major advance in dental pain control.Benefits to patients and operators might include anxietyreduction and a decline in the number of needle-stickinjuries.

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* Tel.: 1 44-191-2228292; fax: 1 44-191-2226137.E-mail address: [email protected] (J.G. Meechan)

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The ideal intra-oral topical anaesthetic should have thefollowing properties:

be non-allergenic; allow pain-free application; remain at site of application; have an acceptable taste; produce reliable anaesthesia; produce sufficient duration of anaesthesia; produce no local damage; produce no systemic toxicity.

Topical anaesthetics are used in dentistry for the follow-ing purposes:

1. to mask the discomfort of local anaesthetic injections;2. to reduce the pain of operative dental procedures;3. to relieve the pain of superficial mucosal lesions (such as

ulcers);4. to anaesthetise skin prior to venepuncture for sedation or

general anaesthesia.

This review considers the use of topical anaesthetics tomask the discomfort of potentially painful oro-dental proce-dures. The application of topical anaesthetics to treat thesymptoms of oral mucosal lesions is not discussed, neitheris the use of mechanical equipment such as jet injectors,thermal methods of surface anaesthesia or extra-oral use.

2. Pharmacology of topical application

Both amide and ester local anaesthetic agents are activewhen applied topically. Indeed the only ester-type localanaesthetics available commercially for use in dental prac-tice in the United Kingdom at present are the topical agentsbenzocaine and amethocaine.

Bergman et al [3] investigated the transfer of radio-isotope labelled lignocaine and prilocaine across the oralmucosa of the dog. They reported that the rate of transferwas proportional to the concentration of the drug, thatincreasing the pH increased the rate of transfer, that theaddition of a detergent to the solution had a biphasic effect(an early increase in rate of transfer followed by a decrease),and that the different solutions did not differ in their abilityto cross the mucosal barrier. Transfer was noted within2.5 min of application.

Adriani et al [1] compared the efficacy of different drugsas topical agents at various sites including the tip of thetongue on human volunteers using electrical stimulation.On tongue they found an effect at 30 s which was notimproved by extending the time of application up to3 min. These workers noted that there was a concentrationof drug above which any increase did not result in improvedefficacy, up to this dose the latency of onset was decreasedand the duration of action increased with increasing dose.They also noted that combining drugs (such as lignocaineand amethocaine) gave no benefit, duration of action being

governed by the longer lasting drug. In order of decreasingduration the clinically useful drugs tested were ametho-caine, cocaine, dibucaine, dyclonine and lignocaine. Theseworkers also noted that the duration of effect varied withmethod of delivery, topical anaesthesia lasting less than halfthe time of an identical dose administered intracutaneously.Similarly, the site of application influenced duration of topi-cal administration in order of increasing duration the tissuestested were skin (no effect), tip of tongue, lip and palate, andconjunctiva. Like Bergman et al [3] they found effectsrelated to pH of the applied agent. They found that theaddition of catecholamine and peptide vasoconstrictors didnot influence the activity of topical anaesthetics. Like Berg-man et al [3] they noted an effect of the addition of deter-gents, these causing a reduction in the latency of onset.Other workers have reported the value of adding absorptionenhancing agents in producing effective topical formula-tions [4]. In total Adriani et al [1] investigated 40 differentagents and concluded that those most effective topicallywere those that were potentially most toxic systemically.

The degree of penetration is governed by the duration ofapplication. Bjerring and Arendt-Nielsen [5] investigateddepth of analgesia in volunteers (using needle insertion toskin) and noted that this was dependent upon the duration ofapplication of the topical anaesthetic.

Local anaesthetics for topical application can be incorpo-rated into a number of different preparations. The type ofpreparation can affect efficacy. Giddon et al. [6] showed thatlower concentrations of lignocaine were needed in filmstrips compared to the concentration in sprays to achievethe same level of analgesia. These workers also demon-strated a dose response to film strip application [6]. Thedifferent methods by which topical anaesthetics may beapplied intra-orally include:

1. as water soluble salts;2. dissolved in organic solvents;3. as oilwater emulsions;4. as eutectic mixtures;5. incorporated into patches and controlled release devices;6. using iontophoresis and phonophoresis;7. incorporated into liposomes.

It is the uncharged, lipophilic portion of the local anaes-thetic (the base) which gains access to nerves, although thecharged moiety is required for binding to the receptor site.Water has good penetrative abilities that are useful in topicalpreparations however the uncharged local anaesthetic mole-cule is poorly soluble in water. In order to increase theconcentration of base in water, oilwater emulsions havebeen developed. The local anaesthetic is dissolved in the oiland then emulsified in an aqueous vehicle. The maximumconcentration of lignocaine that can be obtained in oildroplets is 20% however when lignocaine and prilocaineare combined they produce a eutectic form which canachieve a concentration of 80% of local anaesthetic agent;

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5Table 1Summary of findings of studies investigating the use of topical anaesthetics to disguise the discomfort of local anaesthetic injections (0 no difference between anaesthetic and placebo; 1 significantdifference between anaesthetic and placebo; 1 1 significant difference between different anaesthetic formulations; , no significant difference between different anaesthetic formulations in study withoutplacebo)

Comparison Test method Site and duration of application Subjects Findings Reference

5% tetracaine in liposomes:20%benzocaine

Insertion of needle and injectionof 4% prilocaine

Not reported Volunteers 1 1 Zed et al. [21]

5% lignocaine: EMLA Intraligamentary injection of 2%lignocaine with adrenaline with30 gauge needle (double-blind)

Maxillary first premolar gingivalcrevice for 5 min

Volunteers 1 1 Meechan and Thomason [31]

Placebo: 10% lignocaine: 20%lignocaine

Insertion of 25 gauge needle(double-blind)

Maxillary and mandibularbuccal reflected mucosa for15 min

Volunteers 1 maxilla 1 1 mandible Hersh et al. [11]

Placebo: 5% lignocaine: EMLA 30 gauge needle insertion(double-blind)

Palatal mucosa upper canineregion and buccal mucosa lowersecond premolar region for 2 and5 min

Volunteers 1 2 min 1 1 5 mins Holst and Evers [27]

Placebo: 20% benzocaine: 5%lignocaine


Reflected mucosa upper canineregion for 3 min

Volunteers 1 Rosivack et al. [22]

Placebo: 20% benzocaine: Injection of 2% lignocaine withadrenaline with 30 gauge needle(single-blind)

Palatal mucosa for 2 min Volunteers 1 Vongsavan and Vongsavan [25]

Placebo: 5% lignocaine Insertion of 27 gauge needle(single-blind)

Palatal mucosa for 30 s Volunteers 1 Yaacob et al. [23]

Placebo: 5% lignocaine Injection of local anaesthetic(double-blind)

Various sites (time not recorded) Child patients 1 Carrel et al. [26]

Placebo: EMLA Insertion of 27 gauge needle(double-blind)

Nasopalatine and greaterpalatine formina for 5 min

Volunteers 1 Svennson and Peterson [28]

Placebo: 5% lignocaine: 15%benzocaine 1 1.7%amethocaine: EMLA

5 mm insertion of 27 gaugeneedle (double-blind)

Buccal sulcus upper premolarregion for 2 min

Volunteers 1 Vickers and Punnia-Moorthy[29]

Placebo: EMLA 27 gauge needle insertion(double-blind)

Buccal to lower first premolarfor 2 min

Volunteers 1 Holst and Evers [27]

Placebo: EMLA: Injection of 2% lignocaine withadrenaline using 27 gaugeneedle (single-blind)

Palatal mucosa for 5 min Patients 1 Meechan and Winter [30]

Placebo: 20% benzocaine Injection of 2% lignocaine withadrenaline with 27 gauge needle(double-blind)

Buccal and palatal to maxillarypremolar for 1 min

Volunteers 1 buccal 0 palatal Hutchins et al. [24]

5% lignocaine: EMLA Injection of lignocaine withadrenaline

Maxillary buccal sulcus for5 min

Child patients , Meechan and Donaldson [37]

Placebo: 20% benzocaine Insertion of 25 gauge needle Buccal to maxillary secondpremolar for 3 min

Volunteers 0 Martin et al. [34]

22% benzocaine: 2%amethocaine with18%benzocaine: 5% lignocaine


Palate for 30 s Volunteers 0 Gill and Orr [32]

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Table 1 (continued)

Comparison Test method Site and duration of application Subjects Findings Reference

Placebo: 20% benzocaine: 18%amino-benzoate with 0.1%benzalkonium

Injection of lignocaine withadrenaline with 25 gauge needle(single-blind)

Palatal mucosa for 45 s Patients 0 Keller [33]

Placebo: Sodium phenolate,menthol, thymol, sodiumtetraborate, glycerin,chlorophyll.

Injection of local anaestheticwith a 27 gauge needle

Various sites Patients 0 Pollack [35]

Placebo: Unnamed topicalanaesthetic

Injection of 2% mepivacainewith a 27 gauge needle

Various sites for 3 min Patients 0 Kincheloe et al. [36]

No treatment 20% benzocaine Inferior alveolar nerve blockinjection of 2% lignocaine withadrenaline with 27 gauge needle(single-blind)

Retromolar area for 2 min Patients 0 Meechan et al. [38]

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this is known as EMLA (eutectic mixture of local anaes-thetics) [7].

Controlled release devices [8] are designed to overcomethe uncontrolled pulse of drug delivery which occurs aftertopical application and aim to supply the drug at a prede-termined rate over a specific time period. They can alsodirect delivery so that release only occurs at one surfaceof the preparation.

The intra-oral use of controlled release devices and anaes-thetic patches have been investigated by a number ofauthors. Brook et al. [9] studied the use of a bioadhesiveslow-release patch placed opposite either upper or lowerpremolar teeth. They investigated both soft tissue and pulpalanaesthesia following a 30 min application of the patchwhich contained 50 mg lignocaine in a double-blindplacebo-controlled trial with 9 volunteers (see below).

Taware et al. [10] reported on the use of a saliva activatedbioadhesive patch containing 20 mg lignocaine. In a pilotstudy with 3 volunteers they noted that subjective feelingsof numbness were apparent in 3 min or less and that theanaesthetic effect peaked at between 15 and 20 minalthough an effect was apparent for between 45 and50 min. In a different pilot study with 5 volunteers theyreported that the patch provided more profound gingivalanaesthesia than a 2% lignocaine topical gel although theonset of anaesthesia was quicker with the gel.

Hersh et al. [11] investigated the efficacy and safety oflignocaine patches containing either 10 or 20% active agent(see below).

Iontophoresis is a means of delivering local anaestheticsto deeper tissue after topical application [12]. Positivelycharged drugs such as lignocaine and adrenaline can beencouraged to penetrate the tissue under the influence ofelectrical charge. Gangarosa investigated different localanaesthetics for skin iontophoresis and noted that thepresence of adrenaline increased efficacy [12]. Cocaineiontophoresis of the dental pulp was reported as long agoas 1896 [13]. Gangarosa [14] described the use of ionto-phoresis with lignocaine and adrenaline as a means ofextracting deciduous teeth (see below). More recentlyWon et al. [15] investigated the use of iontophoresis as ameans of delivering 4% lignocaine with 1:50 000 adrena-line in a human study with 5 volunteers. They tested paincontrol on buccal and lingual mandibular mucosa with a25 g load and reported a duration of anaesthesia rangingfrom 25 to 55 min. Phonophoresis is the use of highfrequency radio waves to drive drugs into tissues and hasbeen suggested as a possible method of increasing the effi-cacy of topical applications [16].

Incorporation of local anaesthetics into liposomes hasbeen used as a means of increasing uptake. Liposomes areartificial membranes composed of lipid and aqueous layerssimilar in composition to biological membranes. Thenumber of layers and the size of the liposome can becontrolled depending upon the desired function. A unilam-melar structure is ideal for delivery of a hydrophobic drug,

whereas a multilammelar structure with more aqueousphases is better for incorporation of hydrophilic drugs. Lipo-somes offer the following advantages compared to conven-tional topical delivery [17]:1. better tissue penetration;2. non-allergenic delivery vehicle;3. act as a depot for controlled release of drug;4. protection from metabolism therefore a longer lasting

effect.

Amethocaine incorporated into liposomes has been shownto provide anaesthesia of skin for up to 4 h following a 1 happlication whereas the standard cream preparation wasineffective [18]. Studies reported in the dermatology litera-ture suggest that lignocaine [19] and amethocaine [20]incorporated into liposomes produce as effective anaesthesiaof skin as EMLA. Zed et al. [21] reported on the use ofliposomes to deliver amethocaine topically intra-orally.

3. Studies into the efficacy of topical anaesthetics prior toneedle penetration or local anaesthetic injections

The results of studies investigating the efficacy of topicalanaesthetics in eliminating the discomfort of needle pene-tration or local anaesthetic injection are summarised inTable 1. The studies are described below.

3.1. Studies reporting positive results

Rosivack et al. [22] compared 5% lignocaine to 20%benzocaine and placebo in reducing the discomfort of27 gauge needle penetration (with no injection) in themaxillary buccal fold in the canine region in human volun-teers. They assessed discomfort using a visual analoguescale (VAS) and found that both active agents were signifi-cantly more effective than placebo but did not differ fromone another in reducing needle penetration discomfort.

Yaacob et al. [23] also looked at the use of a topicalanaesthetic to disguise the discomfort of needle penetrationalone. In their study which used a 4-point scale to score painthe stimulus was insertion of a 27 gauge needle into palatalmucosa opposite the second permanent molar tooth involunteers. They compared a 30 s application of 5% ligno-caine to that of placebo and noted a significant reduction indiscomfort with the active agent. This study also comparedthe pain experience between different ethnic groups andfound no difference attributable to race.

Hersh et al. [11] applied adhesive patches containingplacebo or 10 and 20% lignocaine for 15 min to the buccalreflected mucosa in both maxilla and mandible in volun-teers. They measured the pain experienced following inser-tion of a 25 gauge needle using a VAS and found that bothactive patches were superior to placebo in reducing needlepenetration in both jaws. In addition, in the lower arch, the20% lignocaine patch provided a significantly greateranalgesic effect than the 10% patch.

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Hutchins et al. [24] investigated the topical application of20% benzocaine and placebo for 1 min in alleviating thediscomfort of buccal and palatal injections in volunteersusing 27 gauge needles and 2% lignocaine with 1:100,000adrenaline. They showed that the topical anaestheticreduced injection discomfort on the buccal side but notpalatally.

Vongsavan and Vongsavan [25] reported that a 2 minapplication of 20% benzocaine was more effective than aplacebo treatment in reducing the discomfort of palatalinjections of lignocaine with adrenaline in 14 human volun-teers.

Carrel et al. [26] in a double-blind investigation of the useof 5% lignocaine in a commercial presentation and in anexperimental gel delivery system compared the efficacy ofthese preparations to that of placebo in influencing the reac-tion of children aged between 3 and 6 years to intra-oralinjections. Unfortunately the time of topical anaestheticcontact is not detailed, the injections were given by numer-ous operators, and the sites of injection are not mentioned.These authors did not subject their data to statistical exam-ination but by analysing the number of children that did notcry during the injection (180 out of 378 for the activetreatment; 15 out of 172 for placebo), using the Chi Squaretest, a significant positive effect for lignocaine is suggested(x2 78; p , 0:001).

Holst and Evers [27] investigated the effects of 2 and5 min applications of 5% lignocaine and EMLA on thelabial gingiva in the mandibular canine region and the pala-tal mucosa opposite the upper canine in 10 healthy femalevolunteers. They found that there was more pain relief asso-ciated with the penetration of a 30 g needle after a 5 than a2 min application for both treatments; both treatments weremore effective than placebo and at 5 min EMLA was signif-icantly better than 5% lignocaine. In a further trial in whichdiscs impregnated with EMLA were applied for 2 minbuccally to lower first premolars these workers found thatthe pain related to penetration of a 27 gauge needle wassignificantly reduced under the EMLA disc compared tothe placebo.

The effect of EMLA on the pain of palatal needle pene-tration was investigated in a double-blind placebo-controlled study by Svennson et al. [28]. These workersapplied orahesive bandages for 5 min over the greater pala-tine and incisive foramina and measured the pain of27 gauge needle penetration in volunteers using a VAS.They concluded that the needle insertion pain was signifi-cantly reduced by EMLA but not by placebo and that thiseffect was more marked at the greater palatine foramencompared to the incisive foramen.

Vickers and Punnia-Moorthy [29] compared the 2 minapplication of 5% lignocaine, 15% benzocaine with 1.7%amethocaine, and EMLA on the discomfort produced byinsertion of a 27 gauge needle to a depth of 5 mm in themaxillary premolar buccal sulcus in a double-blind split-mouth investigation. They found that their volunteers

reported significantly less pain with all active agentscompared to placebo and concluded that EMLA was themost effective of the topical preparations.

Meechan and Winter [30] compared the efficacy ofplacebo, transcutaneous electronic nerve stimulation(TENS) and a 5 min application of EMLA on palatalmucosa. They found that EMLA was significantly moreeffective than either placebo or TENS in reducing thediscomfort of palatal injections of 2% lignocaine with1:80 000 adrenaline in adult patients having maxillaryteeth extracted.

Meechan and Thomason [31] compared different topicalpreparations as treatments to reduce the discomfort of peri-odontal ligament injections. They found that injectiondiscomfort was less following a 5 min application ofEMLA compared to a similar application of 5% lignocainein a double-blind split-mouth study in volunteers.

Zed et al. [21] reported that topical application of lipo-somes incorporating 5% amethocaine was more effectivethan 20% benzocaine gel in reducing both needle penetra-tion and injection discomfort during administration of 4%prilocaine at contralateral sites (the exact sites and durationof application are not reported).

3.2. Studies reporting negative results

Gill and Orr [32] in a double-blind split-mouth investiga-tion into the effects of the topical application of 22% benzo-caine, 2% amethocaine with 18% benzocaine, 5%lignocaine or placebo for 30 s on reducing 25 gauge needlepenetration into palatal mucosa found no significant differ-ence between any of the active agents and placebo.

Keller [33] performed a study based on the design of Gilland Orr [32] but in addition to penetrating palatal tissue witha 25 gauge needle this worker injected 0.3 ml of lignocainewith adrenaline close to the greater palatine foramen. Theresults of this study on 60 patients, which compared a 45 sapplication of 20% benzocaine, 18% aminobenzoate with0.1% bezalkonium, and placebo, showed no significantdifference in reported pain between treatments.

Martin et al. [34] investigated the pharmacological andpsychological effects on 25 gauge needle penetration oftopical anaesthetics placed in the maxillary buccal sulcusin the premolar region in a modified placebo design. Theseinvestigators compared a 3 min application of 20% benzo-caine to placebo in their study, each volunteer received eachtreatment in a split mouth investigation however half of thevolunteers were told they would be receiving only placeboand the other half were informed they would be receivingthe active agent. Volunteers recorded actual and anticipatedpain on a VAS. These workers reported that those patientswho were expecting to receive placebo anticipated morepain than those who were advised they would have theactive agent applied. However actual pain experience didnot differ between the active and placebo treatments. Inter-estingly the second injection (irrespective of the treatment



applied) was significantly more uncomfortable than the firstinjection. These workers conclude that topical anaestheticshave little pharmacological effect. However, they suggestthat as those programmed to believe they are receiving anactive topical anticipate less pain of injection then a usefulpsychological benefit is obtained. They point out that thepractitioner should appreciate this psychological benefit andnot rely on the pharmacological effect to reduce injectiondiscomfort but use additional psychological approaches.Psychological influences on the efficacy of topical anaesthe-sia have been investigated by Pollak [35]. This workerstudied the effect of suggestion in a sample of 500 dentalpatients and found that, in patients receiving a 15 s applica-tion of a topical anaesthetic prior to injection, those whowere given a verbal reinforcement of the effects of the topi-cal reacted less severely to the injection compared to thosegiven no such information. The results of this study alsoshowed no difference in reaction to the local anaestheticinjection between patients treated with the active topicalagent compared to a similar application of a placebo.

Kincheloe et al. [36] also looked at pain expectation intheir study of the effects of a topical local anaesthetic agent(material and concentration not reported) and placebo onpain perception on mucosa and injection of 2% mepivacainewith a 27 gauge needle. These workers reported no differ-ence in injection experience between active agent andplacebo but found a significant correlation betweenexpected pain experience and actual pain experience. Simi-larly to Martin et al. [34] these workers reported that therewas no difference in pain experience between those patientswho were informed they had received a topical anaestheticand those not given this instruction.

Meechan and Donaldson [37] compared the effects of a5 min application of 5% lignocaine and EMLA in reducingthe discomfort of maxillary infiltration injections in chil-dren. No difference in injection discomfort was notedbetween treatments. It is important to point out that theresults of this study do not refute the use of topical anaes-thesia in children as no comparison was made with aplacebo, however as there was no difference between treat-ments it is included in this section as a negative result.

All of the studies mentioned above have investigated theuse of topical anaesthetics prior to infiltration anaesthesia.Meechan et al. [38] found that 20% benzocaine applied for2 min was no better than no mucosal preparation prior toinferior alveolar nerve block injections with 2% lignocaineand 1:80 000 adrenaline using a 27 gauge needle in an adultpopulation prior to mandibular extractions.

4. The use of topical anaesthetics to reduce thediscomfort of potentially painful intra-oral procedures

4.1. Studies on use in the gingival crevice

The use of local anaesthetics in the gingival crevice to

reduce the discomfort of periodontal ligament injectionswas described above [31]. Other workers have studied theuse of anaesthetic agent at this site to reduce the discomfortof periodontal procedures.

In a double-blind, randomised, split-mouth study Svens-son et al. [39] compared the effects on the discomfort ofscaling of applications for at least 5 min of EMLA andplacebo to the gingival margins in patients with mildchronic periodontitis. These workers reported that EMLAreduced the pain and unpleasantness of scaling in both upperand lower jaws when compared to placebo; the effect onpain however was more marked than the effect on unplea-santness.

The results of a double blind split mouth study [40] usingvolunteers which compared the depth of pain-free probepenetration into the gingival crevice showed that a 5 minapplication of EMLA allowed a significantly greater depthof penetration compared to similar treatment with 5% ligno-caine.

4.2. Studies on use on gingiva

Brook et al. [9] measured sensory changes in the lips andattached gingivae following application of a patch contain-ing 50 mg lignocaine for 30 min. The active patches abol-ished perception to painful stimuli (sharp probing) in a meantime of 7.4 min, sensation returned to normal in a mean timeof 26.4 min following patch removal. Some loss of sensa-tion was noted on the vermilion border and skin surfaces,normal sensation returning to these areas a mean time of22.6 min following patch removal. In two volunteers thearea of mucosa under the patch showed a white appearanceat 24 h which had disappeared at 48 h and was symptomlessthroughout.

Svensson et al. [41] investigated the analgesic efficacyand duration of effect of lignocaine and EMLA on tongueand gingiva labial to the lower incisor teeth using argonlaser stimulation. They measured pain and sensory thresh-olds following a 2 min application of lignocaine and 2, 5,and 15 min applications of EMLA. The greatest increase inpain threshold for all treatments was noted immediatelyafter removal of the topical anaesthetic. The increase insensory and pain threshold was related to the agent applied;EMLA being significantly more effective than lignocaine.The duration of EMLA application was positively related tothe intensity of the effect on tongue (both sensory and painperception being more elevated after 15 min compared to2 min) although such an effect was not apparent on thegingiva. Sensory and pain thresholds were elevated for alltreatments up to 25 min after removal. These authorsconcluded that a 5 min application of EMLA on the tonguegives clinical analgesia for 5 min and that a 2 min applica-tion on the gingiva produces analgesia for 10 min.

Pere et al. [42] investigated the use of 4 g EMLA appliedover 4 min to the gingivae by a toothbrush as a means ofpain control for the removal of arch bars used in intermaxillary



fixation in a double-blind placebo-controlled trial in 45dentate patients. They found that pin-prick sensation wassignificantly less in the EMLA group 5 min after tooth-brushing with the topical compared to the placebo beforeremoval of the arch-bars. However, following removal ofthe arch bars (mean time 19 min after toothbrushing) therewas no difference between treatments in response to pin-pricking of the gingiva. They recorded significantly morepatients with EMLA reported no pain (7/14) compared tothose who received placebo (2/15). They concluded thatEMLA produced significant analgesia for the removal ofarch bars.

Haasio et al. [43] compared the analgesic effects ofEMLA and 10% lignocaine spray on buccal gingivalmucosa on the upper jaw in 10 volunteers. They testedloss of sensation by electrical stimulation and recordedboth sensory and pain thresholds. The treatments did notdiffer in the amount of analgesia they produced. The maxi-mum analgesic effect of EMLA was obtained at a mean timeof 13 min and for lignocaine it was 14 min, normal sensa-tion had returned in most cases by 30 min for each treat-ment. No change in sensory threshold was apparent at anystage with either treatment in this investigation.

4.3. Study into use of topical as sole anaesthetic for biopsyRoller and Ship [44] compared the injection of plain 2%

lignocaine to a 5 min application of a strip containing 20 mglignocaine as anaesthesia for oral mucosal biopsies (eithernormal or ulcerated tissue) in an unblinded study with 20subjects. They reported that both techniques produced simi-lar anaesthetic potency and duration and that subjectivemeasures of surgical bleeding were similar. Despite record-ing similar anaesthetic potency the biopsies performedunder the film were recorded as being significantly morepainful. They noted that pain was not associated with theinitial punch cut but was due to incision at the base of thebiopsy and concluded that this was due to poor penetrationof the topical anaesthetic to the depth of the tissue (thebiopsy specimens were approximately 4 mm deep).4.4. Studies into use of topical anaesthetics to providedentinal/pulpal anaesthesia

Brook et al. [9] looked at changes in response to electricalpulp testing of the teeth adjacent to patches containing50 mg lignocaine or placebo following a 30 min application.All teeth remained responsive to electrical pulp testinghowever those adjacent to the active patches showed signif-icant elevations in pain threshold compared to base-line andwhen compared to those teeth adjacent to placebo patches.

Vickers and Punnia-Moorthy [45] investigated the appli-cation of EMLA, 10% lignocaine, and placebo on theresponse to electrical pulp testing of maxillary central inci-sors. They concluded, although the study was not subjectedto statistical analysis, that EMLA was effective in reducingthe pulpal response as 12 of the 13 volunteers in whom it

was applied showed no response to electrical pulp testingbetween 15 and 30 min of application. However some of thelignocaine and placebo treated cases also showed reductionsin pulpal response including failure to respond under maxi-mum stimulation from the pulp tester.

Vickers et al. [46] performed an uncontrolled pilot studyinto the effectiveness of 1 g topical EMLA as an alternativeto infiltration anaesthesia as pain control for restorativeprocedures on teeth in 12 patients. They reported that75% of subjects obtained adequate analgesia for dril-ling and concluded that this method produced sufficient,but not complete, anaesthesia to allow restorative dentistryto be performed.

Meechan and Donaldson [37] compared placebo andEMLA applied for 5 min to the maxillary buccal sulcuson the response of deciduous teeth to electrical stimulationin a double-blind study. They found no difference betweentreatments. They also looked at the ability of EMLA toeliminate the discomfort of restorative dentistry on decid-uous teeth and reported that 80% of the children studiedrequired supplementary local anaesthetic injections tocomplete treatment painlessly.

Amess et al. [47] reported on the use of topical lignocaineapplied to human dentine. These workers reported that theapplication of a drop of 50% lignocaine solution ontoexposed dentine reduced the response to both air blastingand probing stimuli in a small uncontrolled study with 6volunteers.

De Nunzio [48] reported on the use of 20% benzocaine asa topical application to the dental pulp during endodontictreatment. This author claims great success for the methodbut this paper is merely a description of a technique and isanecdotal.

4.5. Studies into the use of topical anaesthetics as solemeans of anaesthesia for dental extractions

Taware et al. [10] used a bioadhesive delivery system toadminister lignocaine as the sole means of anaesthesia fordental extractions in both adults and children. They appliedpatches containing 20 mg lignocaine to the buccal and pala-tal/lingual gingiva in the apical region of the tooth to beextracted. The patch was maintained in position until thegingiva could be detached from the tooth without pain andthen the extraction was performed. The time to extractiondiffered significantly between the jaws; the mean time forthe maxilla and mandible being approximately 19 and13 min, respectively. In their uncontrolled trial of 49 extrac-tions in 41 patients they achieved successful anaesthesia in40 (81%) of teeth. Despite the fact that no vasoconstrictorwas used post-operative bleeding was reported as normal.

Gangarosa [14] reported on the use of 2% lignocaine with1:50,000 adrenaline administered by iontophoresis for10 min for the extraction of deciduous teeth. This workerreported that 12 out of 13 teeth subjected to this form ofanaesthesia were extracted without discomfort. The author



describes the use of a mouth electrode ( 1 ve charge) cover-ing the teeth and associated mucosa, the indifferent elec-trode ( 2 ve charge) being attached at the wrist.

4.6. Use of topical agents for post-extraction pain reliefGreengrass et al. [49] investigated the use of topical bupi-

vacaine placed over extraction sockets as a method of paincontrol following simple exodontia. These workers reportedthat biting on dental rolls soaked with 7 ml of 0.25% bupi-vacaine with 1:200,000 adrenaline was more effective thanoccluding on saline-soaked rolls in relieving discomfortfollowing extractions under general anaesthesia in childrenaged between 7 and 15 years.

5. Plasma levels following topical anaesthetic application

Plasma levels of anaesthetic agents reported followingintra-oral topical application are summarised in Table 2.

The level of drug entering the circulation after topicalapplication is of interest. Toxic reactions to topicallyapplied local anaesthetics are known to occur [50], indeedfatalities have been reported [51]. It has been claimed thattoxic reactions to local anaesthetics are more common aftertopical than via any other route of administration [51]. It isthe amount of drug that is administered that is importantwith regard to toxicity and topical agents are usually avail-able in concentrations much greater than are found ininjected formulations. Adriani and Campbell [51] provideddata from a study in dogs which showed that entry into thecirculation was quicker after topical administration to thepharynx than following subcutaneous injection, indeed theyconcluded that the entry profile following topical adminis-tration simulated that after rapid intravenous injection(although the peak level was around a third that obtained

after IV injection). Certainly topical administrationachieved much higher peak levels than slow intravenousinfusion of the same dose. Toxicity to lignocaine occurs ata plasma concentration of around 5 mg/ml [52].

Hersh et al. [11] measured plasma lignocaine levels afterthe use of patches containing either 10 or 20 mg of the localanaesthetic. They found that plasma lignocaine levels rosesteadily during the 15 min of patch application and thenremained steady over a period of 30 min from the 15 minsample. Average peak levels were 0.016 mg/ml for the 10%patch and 0.022 mg/ml for the 20% patch; these values arean order of magnitude less than obtained following the intra-oral injection of 2% lignocaine solutions [53,54].

Brook et al. [9] measured plasma lignocaine levels in ninevolunteers following a 30-min application of a patchcontaining 50 mg lignocaine on the buccal gingivae oppo-site the premolar teeth (either upper or lower depending onsubject). They reported peak lignocaine levels occurred 4560 min following patch placement and the highest concen-tration recorded was 0.095 mg/ml. The mean peak level wasaround 0.030 mg/ml.

Pere et al. [42] investigated plasma levels of lignocaineand prilocaine following the application of 4 g EMLA to thegingiva for 4 min using a toothbrush. The plasma levels ofprilocaine were significantly lower than lignocaine (becauseof more rapid metabolism). The highest concentration ofprilocaine being 0.09 mg/ml at 30 min from the start ofthe application; for lignocaine the greatest level was0.26 mg/ml at 15 min.

Haasio et al. [43] studied anaesthetic drug plasma levelsafter application of 4 g of EMLA to upper gingivae with atoothbrush (100 mg lignocaine and 100 mg prilocaine) for4 min compared to 4 50 mg of 10% lignocaine spray to theupper gingivae. They found that anaesthetic absorption wasmore rapid after EMLA but the only significant difference


Table 2Summary of results of studies measuring plasma levels of anaesthetic agents following intra-oral topical administration

Topical agent Amount, duration and locationof application

Mean peak plasma level:concentration and time

Maximum plasma level:concentration and time

Reference

10% lignocaine spray 200 mg sprayed on maxillarygingivae

0.35 mg/ml at 20 min 0.66 mg/ml at 20 min Haasio et al. [43]

10% lignocaine patch 23 mg on premolar buccalreflected mucosa for 15 min

0.016 mg/ml at 15 min Not reported Hersh et al. [11]

20% lignocaine patch 46 mg on premolar buccalreflected mucosa for 15 min

0.022 mg/ml at 15 min Not reported Hersh et al. [11]

Lignocaine patch 50 mg buccal gingivae of bothjaws for 30 min

0.03 mg/ml at 45 min 0.095 mg/ml at 60 min Brook et al. [9]

EMLA 8 g buccal mucosa for 30 min Lignocaine 0.22 mg/ml at40 min

Lignocaine 0.42 mg/ml at 30 min Vickers et al. [46]

Prilocaine 0.13 mg/ml at 40 min Prilocaine 0.22 mg/ml at 30 minEMLA 4 g for 4 min to gingivae both

jawsLignocaine 0.21 mg/ml at30 min

Lignocine 0.26 mg/ml at 15 min Pere et al. [42]

Prilocaine 0.05 mg/ml at 30 min Prilocaine 0.09 mg/ml at 30 minEMLA 4 g for 4 min to maxillary

gingivaeLignocaine 0.18 mg/ml at20 min

Lignocaine 0.47 mg/ml at 5 min Haasio et al. [43]

Prilocaine 0.10 mg/ml at 10 min Prilocaine 0.21 mg/ml at 10 min


was a higher mean plasma concentration of lignocaine at30 min in the 10% lignocaine spray group where the meanplasma lignocaine concentration was 0.35 mg/ml comparedto 0.14 mg/ml in the EMLA group. The highest lignocaineconcentration in the EMLA group was 0.47 mg/ml at 5 mincompared to 0.66 mg/ml in the lignocaine group at 20 min.The highest prilocaine concentration was 0.21 mg/ml at10 min.

Vickers et al. [46] measured the plasma concentrations oflignocaine and prilocaine following the application of 8 g ofEMLA for 30 min to buccal mucosa in 12 volunteers. Peakplasma levels were obtained at 40 min after initial applica-tion for both anaesthetics. The mean peak level for ligno-caine was 0.221 mg/ml and for prilocaine 0.131 mg/ml. Themaximum concentrations recorded in any one patient were0.418 mg/ml (lignocaine) and 0.223 mg/ml (prilocaine).

6. Adverse effects

The application of local anaesthetics seems to producelittle adverse effects on mucosa.

A histological study of the application of 5% lignocaineto the oral mucosa of hamsters for periods up to 24 hrevealed essentially normal epithelium with no signs ofany inflammatory response or tissue oedema [26].

Hersh et al. [11] investigated adverse effects of patchescontaining 10 and 20% lignocaine placed intra-orally andfound no difference between the active treatments andplacebo. Vickers et al. [46] noted no adverse local effectsin any subject following a 30-min application of 8 g EMLAto buccal mucosa. Reports of damage to mucosa are rare,any problems appear to be reversible and symptomless [9].An exception however is the misuse of the anaesthetic agentcocaine. When applied topically on gingiva (a techniquesometimes used to assess purity) this drug can cause ulcera-tion and gingival necrosis due to vasoconstriction [55,56]. Apossible adverse effect of topical anaesthesia was describedin a case report by Pashley and Parsons [57]. These workersdescribe a case of severe pain following application of 5%lignocaine ointment adjacent to vital teeth with exposeddentine. They postulate that the discomfort was producedby an osmotic effect on dentinal tubules by the hypertonictopical preparation.

7. Conclusions

This review has considered a number of possible applica-tions of topical anaesthetics intra-orally in addition to use asa pre-injection treatment. Patients undergoing periodontalprocedures [39], restorative treatment on teeth [45,46],extractions [10,14] and biopsies [44] have all been reportedto have this treatment performed successfully using onlytopical anaesthesia. This would appear to indicate greatadvances in this field. However the evidence from someof the controlled studies reviewed suggest that these agents

are not reliably effective prior to local anaesthetic injec-tions. Although a number of studies show an analgesic effect[11,2131] others have been quoted which show the topicalanaesthetic has no influence [24,3236]. The reasons forsuch equivocal results are many. In the studies referred toa number of different stimuli have been applied to assessanalgesia prior to local anaesthesia, for example someinvestigations have looked at needle penetration only[11,22,23,2729], others have used local anaesthetic injec-tions [33,35,36]. In addition, different needle gauges havebeen utilised and the times of topical anaesthetic applicationare not consistent. The site of the stimulus varies (palate orbuccal sulcus) and finally not all studies randomised theorder of treatment (order of stimulus affects perceiveddiscomfort [34]). Other methods used to assess topicalanaesthetic activity have included alteration in taste sensa-tion [58]. Therefore the evidence suggests that the idealintra-oral topical anaesthetic is not presently available.Two features are apparent in those studies where a conven-tional topical anaesthetic has demonstrated a lack of efficacyprior to infiltration local anaesthetic. Either the topical agentwas applied for a very short time [24,32,33] (less than orequal to a minute), or a wide bore needle (25 gauge) wasused as the stimulus [3234]. Thus, when using acceptedformulations such as 20% benzocaine or 5% lignocaine,success is technique-dependent. Efficacy is improved byusing application times of at least 2 min and by employingneedles of 27 gauge diameter or less. The only study whichshowed that an application time of less than a minute wassuccessful can be criticised in that the sides of active andplacebo treatments were not randomised and this affectspain perception [34].

Few studies have been performed in relation to the effi-cacy of topical anaesthetics prior to intra-oral injections inchildren [26,37]. The only placebo-controlled child studyrecorded [26] used simple subjective measures for efficacyand did not report any statistical analysis, although the datadid suggest a positive effect of the topical agent.

The only study that has investigated the use of topicalanaesthetics prior to deep regional block injections showedno benefit was derived by such treatment [38].

The use of topical anaesthesia in the mouth does notappear to produce serious unwanted effects. Concentrationsof topical anaesthetic up to 10 times greater than containedin dental local anaesthetic solutions produce plasma levelsan order of magnitude below those needed to produce toxi-city. However a cautionary note must be made here. All thestudies reporting plasma levels after intra-oral use of topicalanaesthetics have been performed in adults; plasma levelsfollowing intra-oral topical anaesthetic application in chil-dren have not been recorded. This is an important point asthere is evidence in the medical literature that seeminglylow doses of topical anaesthetic applied to the skin ofyoung children can produce toxicity [50].

Some recent advances, such as the introduction of EMLAand the incorporation of anaesthetics into liposomes appear



to offer exciting possibilities. A number of the studiesreported have shown that EMLA is effective intra-orallyprior to a number of procedures. Indeed, in all the studiesreviewed EMLA is significantly better than placebo at redu-cing the pain of intra-oral injections [2730]. The onlyEMLA study to show no difference between treatmentswas a comparison with 5% lignocaine as a topical anaes-thetic prior to injections in children [37]. Therefore EMLAappears to offer useful properties as an intra-oral topicalanaesthetic. However, it must be stressed that this anaes-thetic is not currently available in a dedicated intra-oralformulation and the manufacturers do not recommend theuse of EMLA on mucosa. The only investigation of the useof liposomes as delivery devices for intra-oral topical anaes-thetics showed encouraging results [21]. Further studies intothe use of liposomes intra-orally are needed.

The most exciting prospects relating to topical anaesthe-sia concern the use of this method as a sole means of paincontrol prior to operative dentistry, periodontal treatmentand oral surgery. This review has presented evidence thata little progress has been made in reaching these goals.There is still considerable work to be performed beforelocal anaesthetic needles can be excluded form the dentalarmamentarium. Nevertheless this is a goal worth pursuingand research and development into topical anaesthetics foruse in dentistry should be encouraged.

References

[1] Adriani J, Zepernick R, Arens J, Authement E. The comparativepotency and effectiveness of topical anesthetics in man. Clinical Phar-macology and Therapeutics 1963;5:4962.

[2] Malamed SF. Handbook of local anesthesia, St Louis, MO: Mosby,1997.

[3] Bergman S, Kane D, Siegal IA, Ciancio S. In vitro and in situ transferof local anaesthetics across the oral mucosa. Archives of Oral Biology1969;14:3543.

[4] Sakamoto, M., Kaho, T., Sadanaga, M., Shimoda, O., Morioka, T.,Mishima, M., Nakano, M. Dermal patch anaesthesia: comparison of10% lignocaine gel with absorption promoter and EMLA cream.Anaesthesia 1993;48:390392.

[5] Bjerring P, Arendt-Nielsen L. Depth and duration of skin analgesia toneedle insertion after topical application of EMLA cream. BritishJournal of Anaesthesia 1990;64:173177.

[6] Giddon DB, Quadland M, Rachwall PC, Springer J, Tursky B. Devel-opment of a method for comparing topical anesthetics in differentapplication and dosage forms. Journal of Oral Therapy Pharmacology1968;4:270274.

[7] Evers H. Present research in local analgesics. British Journal of OralMaxillofacial Surgery 1988;26:390394.

[8] Brook IM, van Noort R. Controlled delivery of drugs. British DentalJournal 1984;157:1115.

[9] Brook IM, Tucker GT, Tuckley EC, Boyes RN. A lignocaine patch fordental analgesia safety and early pharmacology. Journal of ControlledRelease 1989;10:183188.

[10] Taware CP, Mazumdar S, Pendharkar M, Adani MH, Devarajan PV.A bioadhesive delivery system as an alternative to infiltration anaes-thesia. Oral Surgery Oral Medicine Oral Pathology 1997;84:609615.

[11] Hersh EV, Houpt MI, Cooper SA, Feldman RS, Wolff MS, Levin LM.

Analgesic efficacy and safety of an intra-oral lidocaine patch. Journalof the American Dental Association 1996;127:16261634.

[12] Gangarosa LP. Newer local anesthetics and techniques for adminis-tration. Journal of Dental Research 1981;60:14711480.

[13] Morton WJ. Guaiacolcocaine cataphoresis and local anesthesia: anew catophoresis electrode and the Wheeler fractional volt selector.Dental Cosmos 1896;38:3853.

[14] Gangarosa LP. Iontophoresis for surface local anaesthesia. Journal ofthe American Dental Association 1974;88:125128.

[15] Won SH, Ryu HR, Lee SW, Kho HS. Penetration of lidocaine intooral mucosa by iontophoresis and its clinical application. Journal ofDental Research 1995;74:576 Abstract 1404.

[16] Malamed SF. Whats new in local anesthesia? Anesthesia Progress1992;39:125131.

[17] Lener EV, Bucalo BD, Kist DA, Moy RL. Topical anesthetic agents indermatologic surgery: a review. Dermatologic Surgery 1997;23:673683.

[18] Geszetes A, Mezei M. Topical anesthesia of the skin by liposome-encapsulated tetracaine. Anesthesia and Analgesia 1988;67:10791081.

[19] Bucalo BD, Mirikitani EJ, Moy RL. Comparison of skin anestheticeffect of liposomal lidocaine, non-liposomal lidocaine, and EMLAusing 30-minute application time. Dermatologic Surgery1998;24:537541.

[20] Hung OR, Comeau L, Riley MR, Tan S, Whynot S, Mezei M.Comparative topical anaesthesia of EMLA and liposome-encapsu-lated tetracacine. Canadian Journal of Anaesthesia 1997;44:707711.

[21] Zed CM, Epstein J, Donaldson D. Topical liposome encapsulatedtetracaine versus benzocaine: a clinical investigation. Journal ofDental Research 1996;75:247.

[22] Rosivack RG, Koenigsberg SR, Maxwell KC. An analysis of theeffectiveness of two topical anaesthetics. Anesthesia Progress1990;37:290292.

[23] Yaacob HB, Noor GM, Malek SN. The pharmacological effect ofxylocaine topical anaesthetica comparison with placebo. SingaporeDental Journal 1981;6:5557.

[24] Hutchins HS, Young FA, Lackland DL, Fishburne CP. The effective-ness of topical anesthesia and vibration in alleviating the pain of oralinjections. Anesthesia Progress 1997;44:8789.

[25] Vongsavan K, Vongsavan N. Comparison of topical anesthetic geland TENS in reducing pain. Journal of Dental Research 1996;75:248Abstract 1841.

[26] Carrel R, Friedman L, Binns WH. Laboratory and clinical evaluationof a new topical anesthetic. Anesthesia Progress 1974;21:126131.

[27] Holst A, Evers H. Experimental studies of new topical anaesthetics onthe oral mucosa. Swedish Dental Journal 1985;9:185191.

[28] Svensson P, Petersen JK. Anesthetic effect of EMLA occluded withorahesive oral bandages on oral mucosa. A placebo-controlled study,Anesthesia Progress 1992;39:7982.

[29] Vickers ER, Punnia-Moorthy A. A clinical evaluation of three topicalanaesthetic agents. Australian Dental Journal 1992;37:266270.

[30] Meechan JG, Winter RA. A comparison of topical anaesthesia andelectronic nerve stimulation for reducing the pain of intra-oral injec-tions. British Dental Journal 1996;181:333335.

[31] Meechan JG, Thomason JM. A comparison of 2 topical anesthetics onthe discomfort of intraligamentary injections. Oral surgery, oralmedicine and oral pathology 1999;87:362365

[32] Gill CJ, Orr DL. A double blind crossover comparison of topicalanesthetics. Journal of the American Dental Association1979;98:213214.

[33] Keller BJ. Comparison of the effectiveness of two topical anestheticsand a placebo in reducing injection pain. Hawaii Dental Journal1985;16:1011.

[34] Martin MD, Ramsey DS, Whitney C, Fiset L, Weinstein P. Topicalanesthesia: differentiating the pharmacological and psychologicalcontributions to efficacy. Anesthesia Progress 1994;41:4047.

[35] Pollack S. Pain control by suggestion. Journal of Oral Medicine1966;21:8995.



[36] Kincheloe JE, Mealiea WL, Mattison GD, Seib K. Psychophysicalmeasurement on pain perception after administrastion of a topicalanesthetic. Quintessence International 1991;22:311315.

[37] Meechan JG, Donaldson D. The intra-oral use of EMLA cream inchildren: a clinical investigation. Journal of Dentistry for Children1994;61:260262.

[38] Meechan JG, Gowans AJ, Welbury RR. The use of patientcontrolled transcutaneous electronic nerve stimulation (TENS)to decrease the discomfort of regional anaesthesia in dentistry:a randomised controlled clinical trial. Journal of Dentistry 1998;26:417420.

[39] Svensson P, Petersen JK, Svensson H. Efficacy of a topical anestheticon pain and unpleasantness during scaling of gingival pockets.Anesthesia Progress 1994;41:3539.

[40] Donaldson D, Meechan JG. A comparison of the effects of EMLAwcream and topical lidocaine on discomfort during gingival probing.Anesthesia Progress 1995;42:710.

[41] Svensson P, Bjerring P, Arendt-Neilsen L, Kaaber S. Hypoalgesiceffect of EMLA and lidocaine gel applied on human oral mucosa:quantitative evaluation by sensory and pain thresholds to argon laserstimulation. Anesthesia Progress 1992;39:48.

[42] Pere P, Iizuka T, Rosenberg PH, Lindqvist C. Topical application of5% eutectic mixture of lignocaine and prilocaine (EMLAw) beforeremoval of arch bars. British Journal of Oral Maxillofacial Surgery1992;30:153156.

[43] Haasio J, Jokinen T, Numminen T, Rosenberg PH. Topical anaesthe-sia of gingival mucosa by 5% eutectic mixture of lignocaine andprilocaine or by 10% lignocaine spray. British Journal of Oral Maxil-lofacial Surgery 1990;28:99101.

[44] Roller NW, Ship II. Lidocaine topical film strip for oral mucosalbiopsies. Journal of Oral Medicine 1975;30:5558.

[45] Vickers ER, Punnia-Moorthy A. Pulpal anesthesia from an applica-tion of a eutectic topical anesthetic. Quintessence International1993;24:547551.

[46] Vickers ER, Marzbani N, Gerzina TM, McLean C, Punnia-Moorthy

A, Mather L. Pharmacokinetics of EMLA cream application to oralmucosa. Anesthesia Progress 1997;44:3237.

[47] Amess TR, Matthews B, Barrak F, Matthews RW. Topical anesthesiaof dentine in man. Journal of Dental Research 1996;75:270 Abstract2021.

[48] DeNunzio M. Topical anesthetic as an adjunct to local anesthesiaduring pulpectomies. Journal of Endodontics 1998;24:202203.

[49] Greengrass SR, Andrzejowski J, Ruiz K. Topical bupivacaine for paincontrol following simple dental extractions. British Dental Journal1998;184:354355.

[50] Jakobson B, Nilsson A. Methaemoglobinaemia associated with aprilocainelidocaine cream and trimethoprimsulphamethoxazole.A case report, Acta Anaesthesiologica Scandinavica 1985;29:453455.

[51] Adriani J, Campbell D. Fatalities following topical application oflocal anesthetics to mucous embranes. Journal of the American Medi-cal Association 1956;162:15271530.

[52] Foldes FF, Molloy R, McNall PG, Koukal LR. Comparison of intra-venously given local anesthetics in man. Journal of the AmericanMedical Association 1960;172:14931498.

[53] Cannell H, Walters H, Beckett AH, Saunders A. Circulating levels oflignocaine after peri-oral injections. British Dental Journal1975;138:8793.

[54] Goebel WM, Allen G, Randall F. The effect of commercial vasocon-strictor preparations on the circulating venous serum level of mepi-vacaine and lidocaine. Journal of Oral Medicine 1980;35:9196.

[55] Rees TD. Oral effects of drug abuse. Critical Reviews in Oral Biologyand Medicine 1992;3:163184.

[56] Parry J, Porter S, Scully C, Flint S, Parry MG. Mucosal lesions due tooral cocaine use. British Dental Journal 1996;180:462464.

[57] Pashley DH, Parsons GS. Pain produced by topical anesthetic oint-ment. Endodontics and Dental Traumatology 1987;3:8082.

[58] Kutscher AH, Zegarelli EV, Kanig JL, Amundson A. Evaluation oftopical anesthetic agents by taste perception. Journal of Oral Medicine1966;21:8688.



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Intra-Oral Topical Anaesthetics- A Review

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