Intraoral topical anesthesia

JO H N G. ME E C H A N

Local anesthesia is the mainstay of pain control

during intraoral operative procedures. A number of

advances have occurred in relation to drugs and

delivery systems since cocaine was isolated as the

active anesthetic component of cocoa leaves by

Albert Niemann in the middle of the 19th century (18,

104). Although the main role for local anesthetic

drugs in the mouth is by injection they can also be

applied topically. Topical intraoral application can

be used to reduce the discomfort of intraoral local

anesthetic injections; to provide anesthesia for intra-

oral operative procedures; to provide symptomatic

relief from the pain of superficial mucosal lesions

(such as ulcers); or to treat toothache and post-

extraction pain.

The earliest recorded anesthetic effect of isolated

cocaine was topical anesthesia of the tongue,

reported by Niemann in 1860 (18). We have come full

circle in that the latest local anesthetic formulation

designed specifically for periodontal treatments

(Oraqix�) is a topical application (45). This paper will

consider the use and effectiveness of topical anes-

thesia in the mouth before local anesthetic injections,

as the sole means of anesthesia for intraoral proce-

dures, and as a treatment for toothache and post-

operative pain.

Pharmacology of local anestheticdrugs

Those local anesthetics that are injected for the

control of pain during intraoral operative procedures

are classified by their chemical structure into esters

and amides. Ester local anesthetics, such as procaine,

are no longer in routine use as injectable agents

because of the superior qualities of the amide type;

however, esters such as benzocaine and amethocaine

(tetracaine) are employed topically. Ester and amide

anesthetics differ in two important respects. First, in

their potential to produce allergic reactions; second,

in the way they are metabolized.

Ester allergy has been recognized for some time

(114). One study reported that the ester agent ben-

zocaine produced contact sensitivity in 5% of a

sample of 1200 eczematous patients (134). On the

other hand, allergy to amides is thought to be rare

(30, 38) and many so-called allergic reactions are

probably toxic or vaso-vagal (30). This is supported

by the fact that a number of patients reported to be

allergic do not suffer reactions when challenged with

the supposed antigen (32). Nevertheless, a number of

allergic reactions to the amide lidocaine have been

reported (30, 58, 74, 87, 118, 127, 132). These have

ranged from mucosal reactions after topical use (58)

to anaphylaxis (74, 85). Cross reactivity between dif-

ferent amide agents has been reported (30) and it is

pertinent to point out that other components of

dental local anesthetic carpules, such as preserva-

tives, reducing agents and latex, could cause allergy

(5, 91). Fortunately most modern local anesthetics

are preservative-free and latex-free carpules are

available.

Ester local anesthetics are metabolized in the

plasma by pseudocholinesterases and thus have a

relatively short plasma half-life. Amide metabolism is

more complex and takes place mainly in the liver, but

not all amides are metabolized in an identical fash-

ion. The metabolism of the archetypal amide lido-

caine is shown in Fig. 1. Variations to the plan shown

in Fig. 1 are experienced by prilocaine and articaine.

Prilocaine undergoes some biotransformation in the

lungs (9, 13). Articaine, although an amide, under-

goes initial metabolism in plasma by a pseudocho-

linesterase (120). These differences in metabolism

explain why prilocaine and articaine are available in

higher concentrations than lidocaine for injection in

dentistry. Although the higher concentrations may

be more effective (82) there is some concern over

problems of localized toxicity (nerve damage such as

56

Periodontology 2000, Vol. 46, 2008, 56–79

Printed in Singapore. All rights reserved

� 2008 The Author.

Journal compilation � 2008 Blackwell Munksgaard

PERIODONTOLOGY 2000

paresthesia) when injected around nerve trunks (59,

72).

It is important to understand the mechanism of

action of clinically useful local anesthetics. Notwith-

standing their chemical differences, ester and amide

local anesthetics have the same mode of action; they

influence the voltage-gated sodium channel. The

structure of the voltage-dependent sodium channel is

well characterized (25, 26); it is a complex structure

composed of three subunits named a, b1, and b2. The

b units are concerned with modulation of channel

gating and are important in intercellular interactions

(25) while the pore itself is contained in the a unit.

Simplified diagrammatic representations of the asubunit and its configurational changes from rest

through activation to inactivation are shown in

Fig. 2A–C. The a unit comprises four very similar

protein domains (I–IV), each of which has six helical

segments (S1–S6) that traverse the width of the cell

membrane. S1–S3 are negatively charged, S4 is posi-

tively charged, mainly arising from arginine and

lysine residues (146). Activation of the channel occurs

when the S4 segment moves outwards in a spiral path

to open up the channel. A loop between domains III

and IV acts as the inactivation gate (25), demon-

strated by the fact that antibodies directed against

this loop block inactivation (146). The S6 segment is

the proposed site of local anesthetic binding (see

below). When binding occurs, a physical blockade to

sodium entry is created. In simple terms local anes-

thetics act as chemical roadblocks to the entry of

sodium into the nerve cell, although they also prevent

leakage of potassium. By blocking sodium entry, local

anesthetics inhibit nerve cell depolarization and thus

prevent the propagation of nerve cell impulses along

the nerve.

There are two theories of local anesthetic action.

These are the membrane expansion theory and the

specific binding theory. The membrane expansion

theory dictates that the incorporation of the local

anesthetic into the nerve cell membrane causes a

degree of expansion of the membrane and this

physical distortion prevents sodium entry. There may

be some effect of this non-specific action but the

specific binding theory (71) is the method that is

generally accepted as the main mode of action; in

this model the local anesthetic binds to a receptor on

the sodium channel. Good support for this theory is

provided by the fact that different racemic forms of

the same molecule show different pharmacological

activities (146) and that binding ability is directly

related to anesthetic potency (88). Two critical amino

acid residues for local anesthetic binding (Phe 1764

and Tyr 1771) have been located on the S6 segment of

domain 4 in the a subunit (25). Access to the binding

site is from within the cell (25) and entry into the cell

requires a lipophilic uncharged moiety to enter the

nerve cell. Access to the binding site is easiest when

the nerve cell is in the inactivated configuration (63,

146). It has been suggested that the binding of local

anesthetic molecules is 17 times lower for resting

channels than for inactivated channels (146). The

more regularly a nerve fires the more times it adopts

the inactivated form so rapidly firing neurons are the

most susceptible to the action of local anesthetics.

This gives rise to the phenomenon known as use-

HN 2

HC 3

HC 3

C2H5

C2H5NHC 2C

O

HN

HC 3

HC 3

H

C2H5

NHC 2C

O

HN

HC 3

HC 3

HC 3

HC 3

OH

noitalyklaed-N

sisylordyH

noitalyxordyH

eniacodiL

edidilyxenicylglyhteonoM

enidilyx-6,2

enidilyx-6,2-yxordyh-4HN 2

Fig. 1. The metabolism of lidocaine.

57

Intraoral topical anesthesia

dependent (or frequency-dependent) block. This act

of binding maintains the sodium channel in the

configuration that it adopts during the refractory

phase of the nerve firing cycle (Fig. 2C). In this for-

mation any further stimulation will not result in

depolarization. Specific binding is achieved by

charged molecules, so the anesthetic must be in the

charged form to be active.

The ability of local anesthetics to exist as both

charged and uncharged portions is possible because

they are weak bases. The portion that is present as an

uncharged base is governed by the pH of the medium

and the pKa of the molecule. The uncharged part

traverses the nerve cell membrane and re-equilib-

rates to release the charged portion within the cell

and this gains access to the binding site.

Sodium channels are not all identical in structure.

At present, nine different voltage-gated sodium

channels have been identified (24). These are sus-

ceptible to different pharmacological actions and

this, together with the fact that drug-binding sites are

being characterized (41), suggests that it should be

possible to develop drugs that are highly specific, for

example it should be possible to increase affinity for

peripheral nerves rather than cardiac tissue. In this

way, local anesthetic drugs with less cardiotoxicity

(see below) could be developed. The heterogeneity of

sodium channels means that there is a variation in

the efficacy of local anesthetics and is one explana-

tion as to why the presence of inflammation, which

encourages the development of neural tissue into

areas of inflammation, reduces the effectiveness of

local anesthetics as these new nociceptors have

sodium channels that are less sensitive to the action

of local anesthetics (63).

Adverse effects of local anesthetics

The problem of allergy was discussed above. Other

unwanted effects are toxicity and drug interactions.

The topic of drug interactions is covered in the paper

by Hersh & Moore in this volume (69). Toxicity may

be systemic or localized. Localized toxicity presents

as nerve damage. This adverse effect of local anes-

3

21

4 5

6

3

2 1

4 5

6

I

I I

I I I

V I

I

II

III

VI

3

21

45

6

I

II

III

VI

A

B

C

Fig. 2. (A) The resting state of the a unit of the sodium

channel showing the pore surrounded by the four

domains each containing six protein segments that tra-

verse the membrane. The entry of the S4 segments into

the channel prevents sodium entry and thus maintains

the resting potential. (B) The channel during the activa-

tion phase when the obstruction to sodium entry has been

removed by movement of the S4 segments into the body of

the membrane. (C) The inactivated configuration when a

loop between domains III and IV blocks sodium entry.

This is the configuration that is maintained with local

anesthetic binding.

58

Meechan

thetics on nerves is concentration-dependent and

has been demonstrated in vivo with differing con-

centrations of lidocaine (79). This has clinical impli-

cations because there is some evidence that more

concentrated solutions, such as 4% articaine and 4%

prilocaine, cause a greater prevalence of long-lasting

paresthesia, especially of the lingual nerve. (59, 72).

Some have criticized these findings (99), noting that

large-scale studies have shown no difference in the

production of paresthesias following the intraoral

injection of 2% lidocaine and 4% articaine (100). The

jury is still out on this debate and undoubtedly more

work will be performed in this important area.

Local anesthetics are not specific in their action.

They will affect tissues other than peripheral sensory

nerves, thus adverse effects in other areas can ensue.

Toxic effects of local anesthetics occur mainly in the

central nervous and cardiovascular systems. The

central nervous system is particularly sensitive to

local anesthetics; plasma concentrations that do not

affect transmission in peripheral nerves can affect

the central nervous system. A study that investigated

the levels of lidocaine required to produce central

nervous system toxicity in humans concluded that

the critical plasma level was 5 lg ⁄ ml (40). At low

doses the toxic effect is excitatory as a result of the

anesthetic blocking inhibitory activity; at higher

doses the effect is depressant, for example uncon-

sciousness. Fatalities as a result of local anesthetic

overdose are a result of the effect on the central

nervous system, namely respiratory arrest (92). Any

effect on the central nervous system will be deter-

mined by a number of factors, such as the concurrent

use of other central nervous active agents, for

example the convulsive threshold of lidocaine is

raised by concurrent use of diazepam (31).

The effects of local anesthetics on the cardiovas-

cular system can be direct or indirect. The latter

occurs as a result of inhibition of the autonomic

fibers that regulate cardiovascular function. Early

signs of cardiovascular toxicity are a slowing of the

pulse. Further inhibition of conduction leads to

varying degrees of block, arrhythmias, and ventricu-

lar fibrillation (90).

Toxicity is avoided by using sensible doses and

ensuring that intravascular injection is avoided. The

maximum doses of the local anesthetics used for

injection in dentistry are shown in Table 1. These

doses are those recommended when vasoconstrictor-

free solutions are used. Although the addition of a

vasoconstrictor, such as epinephrine, will reduce

systemic uptake of local anesthetics, the downside is

that epinephrine has been shown to reduce the

concentration of lidocaine needed to produce central

nervous system effects (145, 154). Thus the doses

given in Table 1 are suggested as a wise maximum. As

a working rule of thumb one-tenth of a cartridge per

kilogram of patient body weight approximates to the

safe maximum dose for most formulations. The

treatment of local anesthetic overdose is outlined in

Table 2.

Methemoglobinemia

Methemoglobinemia is an unwanted effect of a

number of local anesthetics, but is mainly associated

with prilocaine and benzocaine (2, 62). Methemo-

globinemia can cause cyanosis. It is a consequence of

the oxidation of hemoglobin from the ferrous to the

ferric state, leading to an inability to transport

oxygen. Kreutz & Kinni (89) reported a case of met-

hemoglobinemia in a healthy adult who received

632 mg of prilocaine with epinephrine. Crawford (29)

Table 1. Maximum recommended doses for theinjectable local anesthetics used in dentistry

Drug and

concentration

Recommended

maximum dose

(mg ⁄ kg)

(Ceiling in mg)

Amount (mg)

in 1.8-ml

(2.2-ml)

carpule

0.5% Bupivacaine 1.3 (90) 9 (11)

1.5% Etidocaine 8.0 (400) 27 (33)

2% Lidocaine 4.4 (300) 36 (44)

3% Lidocaine 4.4 (300) 54 (66)

2% Mepivacaine 4.4 (300) 36 (44)

3% Mepivacaine 4.4 (300) 54 (66)

3% Prilocaine 6.0 (400) 54 (66)

4% Prilocaine 6.0 (400) 72 (88)

4% Articaine 7.0 (500) 72 (88)

Table 2. Management of local anesthetic overdose

• Stop the procedure

• Reassure the patient

• Lie the patient flat

• Monitor and record vital signs

• Administer oxygen

• Give intravenous fluids

• Give intravenous anticonvulsants

• Perform basic life support

59

Intraoral topical anesthesia

reported that the injection of the maximum recom-

mended dose of prilocaine (400 mg) resulted in <1%

of the total hemoglobin being converted to methe-

moglobin at 90 minutes post injection; this is

considered a physiological level (95). Methemoglo-

binemia has been reported after topical application

of prilocaine and benzocaine (see below); the man-

agement of methemoglobinemia is the intravenous

infusion of methylene blue at a dose of 1–2 mg ⁄ kg

over a 5- to 10-minute period (62).

Pharmacology of topicalapplication of local anesthetics

When applied topically, anesthetic agents must cross

tissue barriers to get to their site of action. To achieve

suitable amounts of drug at the site of action it is

necessary to use concentrations that are higher than

those normally injected. This has an impact on the

production of systemic toxicity, as rapid and exten-

sive absorption can occur. Animal experiments have

demonstrated the transfer of lidocaine and prilocaine

across oral mucosa within 2.5 minutes of application

(11).

Not all local anesthetics are active when applied to

surface tissues, procaine for example does not

achieve topical anesthesia at clinically acceptable

concentrations (4, 11, 12). Both amide and ester local

anesthetic agents can be active when applied topi-

cally. In addition non-ester, non-amide agents are

used as topical anesthetics, for example dyclonine is

a ketone. The agents that are most effective topically

are those that are potentially most toxic systemically

(4), this limits the choice.

The duration of anesthesia following topical

application is less than that of the same dose depos-

ited intracutaneously. Adriani et al. (4) reported

that the duration of action of 1% tetracaine was

53 minutes after topical application compared with

120 minutes after subcutaneous injection.

Factors affecting efficacy

A number of in vitro and in vivo studies in both

animals and humans have shown that a variety of

factors influence the action of topical anesthetics.

The drug

Adriani et al. (4) studied a number of different topical

anesthetics in human volunteers. They used electrical

stimulation as the test method. These workers

reported that the longest-acting drugs were those

with the slowest onset. When different drugs were

combined (lidocaine and tetracaine) the duration of

anesthesia was determined by the longer-lasting

drug, and no benefit was derived. This finding is in

contrast to later work, which has shown increasing

efficacy with certain combinations such as lidocaine

and prilocaine (see below). In order of decreasing

duration the clinically useful drugs tested were

amethocaine, cocaine, dibucaine, dyclonine, and

lidocaine.

Concentration

The study of Adriani et al. (4) showed that although

the onset and duration of local anesthetic action were

concentration-dependent, there was a ceiling dose

above which these factors did not vary. An in vivo

study in dogs (11) showed that the plasma level

of lidocaine, not surprisingly, was raised with

increasing concentration of the topical agent. When

a concentration of 12.5% was applied to lingual

mucosa the average rate of transfer into plasma

was 0.0017 mg% ⁄ minute; this increased to

0.007 mg% ⁄ minute when the concentration was

doubled.

A dose response has been shown by a number of

workers. Giddon et al. (54) used electrical stimulation

of the attached gingiva in the maxillary premolar

region of human volunteers to assess the efficacy of

different concentrations of lidocaine in film strips in

a placebo-controlled single-blinded study. They

found a positive dose response for both depth and

duration of anesthesia. Hersh et al. (67) compared

the efficacies of intraoral patches containing 10%

and 20% lidocaine or placebo placed on the man-

dibular buccal gingiva in human volunteers and

noted that the more concentrated material was

significantly more effective than placebo after a 2.5-

minute application. The 10% patch took 5 minutes to

achieve a similar result. They demonstrated a positive

dose response throughout the 45 minutes of that

trial.

pH

As it is the un-ionized form of the drug that diffuses

across tissues to get to the site of action and local

anesthetics are weak bases, then an increase in pH

should increase the rate of diffusion by increasing

the amount of un-ionized base. In an in vitro exper-

iment using dogs (11) the rate of transfer of 1%

60

Meechan

lidocaine across the oral mucosa increased from

0.05 mg ⁄ 5 minutes at pH 5.9 to 0.07 mg ⁄ 5 minutes

at pH 8.6. Similar results were reported for prilocaine.

Additives

Adriani et al. (4) reported that the addition of

catecholamine and peptide vasoconstrictors did

not influence the activity of topical anesthetics.

The addition of 1:10,000 epinephrine or vasopres-

sin did not affect the duration, onset or depth of

topical anesthesia provided by cocaine or tetra-

caine.

The addition of detergents has been shown to both

increase and decrease the onset of anesthesia when

combined with topical anesthetics. Some studies

have shown a decrease in onset time (4), while others

(11) demonstrated that detergents inhibited onset.

Bergman et al. (11) noted that the effect of the

detergent cetylpyridinium chloride was concentra-

tion-dependent. At low concentrations of cetylpy-

ridinium chloride (0.1%) the anesthetic action was

enhanced and with higher concentrations (1%)

anesthesia was inhibited. Other workers (83) have

noted benefits by adding absorption-enhancing

agents to topical anesthetic formulations; they found

that the addition of the glycyrrhiza derivative

glycerrhetinic acid monohemiphthalate disodium

increased the efficacy of 10% lidocaine in reducing

the discomfort of skin pin-prick sensation in humans.

A later study (136) showed that this enhanced lido-

caine preparation was as effective as EMLA (eutectic

mixture of local anesthetics; see below) in reducing

skin pin-prick pain in humans.

Duration of application

The duration of application of the anesthetic influ-

ences the amount of penetration. This has been

shown in a volunteer study (12) using needle inser-

tion into skin in which workers measured the depth

of penetration of an 18-gauge needle through skin at

which pain was reported following the application of

a mixture of lidocaine and prilocaine (EMLA) or

placebo. They noted that increasing the time of

application increased the depth at which pain per-

ception began. Another human study (67) using an

intraoral application of 10% or 20% lidocaine in a

bioadhesive patch showed increasing relief from pin-

prick pain with increased time of application. The

authors of that study suggested that the duration of

residual anesthesia was dependent upon the duration

of application.

Site

Studies in human volunteers (4) have shown that the

site of intraoral application governs the onset time

and duration of anesthetic action after topical

application. Anesthesia to electrical stimulation was

apparent on the tongue after a 30-second application.

This was not improved by extending the time of

application up to 3 minutes. Duration of intraoral

anesthesia increased from tip of tongue to lip to

palate, although these were all less than the duration

after conjunctival application.

One aspect that makes intraoral sites vary in their

susceptibility to topical anesthetics is the degree of

keratinization of the mucosa. The palatal mucosa is

much more keratinized than the buccal sulcus.

Regimens that produce anesthesia of buccal sulcus

mucosa have no effect on the palate (74, 76). It is

not only the extent of keratinization that governs

efficacy. One study has shown that the mandibular

buccal sulcus is more rapidly anesthetized following

topical application compared with the equivalent

zone in the maxilla (67). The results of a retro-

spective study of 703 dental patients receiving

maxillary infiltration injections with or without 20%

benzocaine topical anesthetic applied for 1 minute

suggested that the topical anesthetic was effective in

reducing the discomfort of needle penetration in the

maxillary lateral incisor region, but had no influence

in this regard in the maxillary molar buccal sulcus

(119).

Formulations

There are a number of different formulations of

topical anesthetic for intraoral use. The anesthetic

may be present: as a water-soluble salt; dissolved in

organic solvents; as an oil–water emulsion; as a

eutectic mixture; incorporated into patches and

controlled-release devices; or incorporated into

liposomes.

The type of preparation affects it efficacy. A human

volunteer study showed that less lidocaine needed to

be incorporated into a film-strip compared with the

doses in a spray or ointment to achieve a similar

anesthetic effect on attached gingiva (54). In addi-

tion, incorporation into film strips increased the

duration of topical anesthetic action when compared

with ointments and sprays (54).

As mentioned above, local anesthetics achieve their

effect by binding to specific receptors in the sodium

channel in nerve cells. This requires the agent to be in

a charged form; however, it is the uncharged (base)

61

Intraoral topical anesthesia

form that gains access to the inside of the nerve cell

(the site from which the anesthetic gains access to its

site of action). Water possesses the good penetrative

properties that are important in the diffusion of

topical preparations; however, the uncharged local

anesthetic molecule is poorly soluble in water. This is

overcome by using oil–water emulsions, which

effectively increase the concentration of base in the

water. The anesthetic is dissolved in oil and then

emulsified in an aqueous vehicle. The maximum

concentration of lidocaine that can be obtained in oil

droplets is 20%; however, when lidocaine and prilo-

caine are combined they produce a eutectic form that

achieves an anesthetic concentration of 80%. This is

known as EMLA (eutectic mixture of local anesthet-

ics) (37).

When applied as ointments or creams the local

anesthetic is released from all surfaces of the applied

load. The amount entering the mucosa is therefore

uncontrolled. To overcome this, controlled release

devices (16) have been designed to discharge the

agent from one surface at a predetermined rate.

These devices have been used intraorally in a number

of studies (15, 67, 144).

Another method used to increase penetration after

application of topical anesthetics is incorporation of

the drug into liposomes (93). These are artificial

membranes consisting of uni- or multilamellar

concentric bilayers that are formed when phospho-

lipids are suspended in aqueous solution (10). Thus

they are similar in composition to biological mem-

branes. Liposome structure can be varied, depend-

ing upon the function required, by altering the

number of layers. They can be used to deliver

both water and lipid-soluble drugs. Delivery of a

hydrophobic drug is best served by a unilamellar

structure; a multilamellar construction with more

aqueous phases is better for the incorporation of

hydrophilic drugs. In addition to offering increased

penetration, other advantages of liposomes include

decreasing the effective dose, prolonging the action

of drugs as they protect the drug from metabolism

(34, 138) and decreased systemic toxicity (14). They

have been investigated in medicine both as inject-

able forms (34) and as topical applications to skin

(112) and cornea (137). They have been investigated

intraorally as a means of delivering corticosteroids

in animal models (64).

The use of liposomes to deliver local anesthetics

has been investigated by a number of authors. The

increased efficacy afforded by liposomes has been

demonstrated in skin where a standard application of

amethocaine has been shown to be ineffective

whereas the drug incorporated into liposomes pro-

vided anesthesia (53). Similarly, lidocaine (17, 23) and

amethocaine (75) incorporated into liposomes pro-

duce anesthesia of the skin that is as effective as

EMLA (see below). The use of liposomes for the

delivery of local anesthetics intraorally has been

reported in two studies. One (155) compared lipo-

somes containing 5% amethocaine with 20% ben-

zocaine in a double-blind split-mouth trial as a

means of disguising intraoral local anesthetic injec-

tion pain. These workers reported that the liposome

formulation significantly reduced the discomfort of

needle penetration and infiltration of anesthesia. The

other study (42) compared 1% ropivacaine incorpo-

rated into liposomes with plain 1% ropivacaine,

EMLA and 20% benzocaine in combating intraoral

pin-prick discomfort. The liposome preparation

produced longer-lasting anesthesia than the plain

ropivacaine and 20% benzocaine and was similar in

effect to EMLA.

Iontophoresis and phonophoresis

Another method of directing the diffusion of anes-

thetics after topical application is the use of ionto-

phoresis (50). Iontophoresis employs an electrical

charge to increase transportation of ionized mate-

rials across membranes. Local anesthetics such as

lidocaine have a positive charge so penetration into

tissue can be encouraged using iontophoresis. The

method has been employed in dentistry and medi-

cine to improve topical anesthesia, for example

iontophoretically applied 4% lidocaine was more

effective than topical lidocaine in reducing the

discomfort of venous cannulation and the injection

of propofol in the dorsum of the hand (135). The

extent of local anesthetic entry has been shown to

be directly related to the voltage in an animal

model (61). Such a phenomenon, using cocaine for

pulpal anesthesia, was described in the late 19th

century (115). Gangarosa (49) used iontophoresis

with lidocaine and epinephrine when extracting

deciduous teeth (see below). Won et al. (152)

reported the use of iontophoresis to deliver 4%

lidocaine with 1:50,000 epinephrine for soft tissue

anesthesia of buccal and lingual mandibular

mucosa in a human study with five volunteers.

They reported duration of anesthesia ranging from

25 to 55 minutes. Another method that could be

used to increase penetration is phonophoresis. This

uses high-frequency radio waves and has been

suggested as a possible method of increasing the

efficacy of topical applications (98).

62

Meechan

The use of topical anesthetics toreduce the discomfort of intraorallocal anesthetic injections

The use of topical anesthetics before injections is

common in dentistry. A recent study of over 500 UK

general dental practitioners reported that 95% of

them used topical anesthesia before injections, 28%

of the total sample used this pretreatment before all

injections (28). Lidocaine and benzocaine were the

most commonly used agents.

The benefits of topical anesthetics may not be

entirely pharmacological…a psychological advantage

may accrue. Martin et al. (102) reported that subjects

who were informed that they were to receive a topical

anesthetic anticipated less injection pain than those

not offered such guidance. Another study found a

significant correlation between expected pain expe-

rience and actual pain experience (86). Similarly,

Pollack (124) studied the effect of suggestion in a

sample of 500 dental patients following topical

anesthetic application. This worker found that

patients who were given a verbal reinforcement of the

effects of topical anesthesia reacted less severely to

local anesthetic injection compared with those given

no such information.

A pharmacological effect can be determined in

well-designed placebo controlled trials or in dose–

response studies. A number of investigations have

compared topical anesthetics with placebo intra-

orally and the results are conflicting. Some show

positive benefits from the use of topical anesthesia

before needle insertion and others do not. The rea-

sons for discrepancies include variations in the site

and duration of application, choice of material

(including formulation), and the fact that no �gold

standard� stimulation test has been agreed.

There are two aspects of local anesthetic injections

that can cause pain. These are needle insertion and

deposition of solution. A number of studies have

investigated the effects of topical anesthetics on

needle insertion in isolation and on the entire injec-

tion experience. These studies are described below.

Conventional intraoral topicalpreparations

Needle penetration studies

A double-blind, split-mouth investigation into the

effects of the topical application of 22% benzocaine,

2% amethocaine with 18% benzocaine, 5% lidocaine

or placebo for 30 seconds on reducing 25-gauge

needle penetration discomfort into palatal mucosa

found no significant difference between any of the

active agents and placebo (55). One study (47) com-

pared 20% benzocaine and 60% lidocaine with pla-

cebo (but not with each other) during a 20-minute

application in the anterior maxillary labial gingiva.

The results of that study showed no difference

between placebo and 20% benzocaine when a

30-gauge needle was inserted down to bone in this

region; however, the 60% lidocaine preparation was

superior to placebo in a similar test.

Martin et al. (102) investigated the efficacy of

topical anesthesia in masking the discomfort of

25-gauge needle penetration in the maxillary buccal

sulcus in the premolar region in a modified placebo

design; a 3-minute application of 20% benzocaine

was compared with placebo. Volunteers received

each treatment in a split-mouth investigation;

however half of the volunteers were told they would

be receiving only placebo and the other half were

informed they would be receiving the anesthetic.

Participants recorded actual and anticipated pain on

a visual analogue scale. The results showed that those

volunteers who were expecting to receive placebo

anticipated more pain than those who were advised

they would have the active agent applied. Actual pain

experience did not differ between the active and

placebo treatments. These workers concluded that

topical anesthetics have little pharmacological effect.

Three-minute applications of 5% lidocaine or 20%

benzocaine have been shown to be significantly more

effective than placebo in reducing the discomfort of

27-gauge needle penetration in the maxillary buccal

fold in the canine region in volunteers (133). In that

study there was no difference in efficacy between the

active drugs. Another study (153) investigated 27-gauge

needle penetration in palatal mucosa in the second

molar region following a 30-second application of

5% lidocaine or placebo. The results showed a signi-

ficant reduction in discomfort with the active agent.

The effectiveness of different quantities of lido-

caine contained in adhesive patches in reducing the

discomfort of 25-gauge needle penetration intra-

orally was studied by Hersh et al. (67) in a placebo-

controlled study. Active patches contained 10% or

20% lidocaine. The patches were applied to the

buccal reflected mucosa in both maxilla and mandi-

ble in volunteers. Both active patches were superior

to placebo in reducing needle penetration in both

jaws. A dose response was apparent as the 20%

formulation provided significantly greater anesthesia

compared with the 10% patch.

63

Intraoral topical anesthesia

A double-blind randomized placebo-controlled

trial with 40 subjects (20) investigated the efficacies

of a 20% lidocaine patch applied for 15 minutes and

the 30-second application of a benzocaine gel in

reducing 25-gauge needle stick pain in the buccal

gingiva in the bicuspid-molar region of either jaw.

The needle was inserted to periosteum. When com-

paring five-point verbal pain and visual analog scale

scores the lidocaine patch was superior to placebo in

reducing needle-stick pain in both jaws; benzocaine

was significantly better than placebo in the mandible

but not in the maxilla. The lidocaine patch was sig-

nificantly more effective than the benzocaine gel at

reducing needle-stick discomfort in both jaws. In a

further double-blind placebo-controlled studies the

same workers (21) increased the application time of

the benzocaine gel to 1 minute and compared this

with the 15-minute application of the 20% lidocaine

patch using a verbal rating score. As in the study

above, the lidocaine patch was superior to placebo

and benzocaine gels in countering the pain of 25-

gauge needle insertion to the periosteum; however,

the benzocaine did not differ significantly from pla-

cebo in this trial. These workers (21) also compared

the discomfort of 25-gauge and 27-gauge needle stick

in the maxillary premolar–molar region following the

15-minute application of a patch containing 20%

lidocaine or placebo. There was no difference in

needle-stick discomfort between gauges; however the

active patch was more effective than placebo in

reducing discomfort.

Zed et al. (155) reported that 5% amethocaine in

liposomes was more effective than 20% benzocaine

in reducing the discomfort of needle penetration

before local anesthetic injections but needle gauge

and time of application were not reported.

Nakanishi et al. (116) reported that a 4-minute

application of 20% benzocaine was significantly

more effective than placebo in reducing the dis-

comfort of 30-gauge needle penetration in the

mandibular buccal sulcus in the canine region in a

blinded parallel study. A similar study using 27-gauge

needles inserted in the pterygotemporal depression

to mimic regional block anesthesia showed no dif-

ference between placebo and 20% benzocaine after a

4-minute application (116).

Injection studies

Pollack (124) studied the effects of a 15-second applica-

tion of a topical anesthetic or placebo before injection

in 500 patients and showed no difference in reaction

to the local anesthetic delivery between treatments.

Another investigation (76) studied the topical app-

lication of 20% benzocaine and placebo for 1 minute

for reducing the discomfort of buccal and palatal

injections of 2% lidocaine with 1:100,000 epinephrine

using 27-gauge needles in volunteers. The results

showed that the topical anesthetic reduced injection

discomfort on the buccal side but not palatally.

Keller (84) investigated a 45-second application of

the same topical anesthetics used in the study of Gill

& Orr (55) (described above) before the injection of

0.3 ml lidocaine with epinephrine close to the greater

palatine foramen with a 25-gauge needle. The results

of this study on 60 patients showed no significant

difference in reported pain between treatments with

20% benzocaine, 18% aminobenzoate with 0.1%

benzalkonium, and placebo.

Kincheloe et al. (86) investigated the effects of a

topical local anesthetic agent (material and concen-

tration not reported) and placebo on pain perception

on mucosa and injection of 2% mepivacaine with a

27-gauge needle. They reported no difference in injec-

tion experience between active agent and placebo.

Fukuyama et al. (47) investigated the abilities of

20% benzocaine and 60% lidocaine applied topically

for 20 minutes in reducing the discomfort of the

injection of 0.9 ml 2% lidocaine with 1:80,000 epi-

nephrine in the maxillary anterior labial gingivae. The

benzocaine was no better than placebo; however, the

60% lidocaine formulation decreased visual analogue

scale scores for injection compared with placebo. The

rather long application time in this study was chosen

by the authors because periods shorter than this

failed to show any efficacy. They note that this is an

unreasonable time clinically.

One study (155) compared the effectiveness of the

topical application of liposomes incorporating 5%

amethocaine with 20% benzocaine gel in reducing

both needle penetration and injection discomfort

during administration of 4% prilocaine at un-named

contralateral sites intraorally. These authors noted

that the liposome regimen was more effective in

reducing discomfort.

Carr & Horton (21) compared the discomfort of the

injection of 2% lidocaine with 1:100,000 epinephrine

following the 15-minute application of a patch con-

taining 20% lidocaine or placebo in the gingiva in the

maxillary premolar–molar region with both 25- and

27-gauge needles. The active patch was more effec-

tive than placebo in reducing injection discomfort.

All of the studies mentioned above have investi-

gated the use of topical anesthetics before infiltration

anesthesia. Two studies have investigated the use

of topical anesthetics before inferior alveolar nerve

64

Meechan

block injections, which necessitate deeper needle

penetration. Meechan et al. (109) found that 20%

benzocaine applied for two minutes was no better

than no mucosal preparation before inferior alveolar

nerve block injections with 2% lidocaine and 1:80,000

epinephrine using a 27-gauge needle in an adult

population before mandibular extractions. The data

from a retrospective study of 1635 dental patients

who received inferior alveolar nerve blocks (27-gauge

needle) with or without 20% benzocaine topical

anesthetic for one minute (119) suggested that the

topical anesthetic had no effect on needle insertion

discomfort.

Comparison of positive and negative response

studies

The results of the needle penetration and injection

studies described above are summarized in Tables 3

and 4, which separate them into those showing

positive and no difference from placebo. When the

Tables are compared some differences are apparent.

Negative findings are more common when the palate

Table 3. Studies showing no difference between effects of topical anesthetic and placebo in reducing needlepenetration or local anesthetic injection discomfort

Agents Duration Site Test Reference

20% Benzocaine,

5% Lidocaine

30 seconds Palate 25-g needle penetration (54)

20% Benzocaine 30 seconds Maxillary buccal 25-g needle penetration (20)

20% Benzocaine 45 seconds Palate Injection with 25-g needle (84)

20% Benzocaine 1 minute Palate Injection with 27-g needle (76)

20% Benzocaine 1 minute Maxillary and mandibular buccal 25-g needle penetration (20)

20% Benzocaine 3 minutes Maxillary buccal 25-g needle penetration (86)

20% Benzocaine 3 minutes Maxillary buccal 25-g needle penetration (102)

20% Benzocaine 4 minutes Pterygotemporal depression 27-g needle penetration (116)

20% Benzocaine 20 minutes Maxillary buccal 30-g needle penetration (47)

20% Benzocaine 20 minutes Maxillary buccal Injection with 30-g needle (47)

Table 4. Studies showing positive effects of topical anesthetic over placebo in reducing needle penetration orlocal anesthetic injection discomfort

Agents Duration Site Test Reference

5% Lidocaine 30 seconds Palate 27-g needle penetration (153)

20% Benzocaine 30 seconds Mandibular buccal 25-g needle penetration (20)

20% Benzocaine 1 minute Maxillary buccal injection with 27-g needle (76)

5% Lidocaine 2 minutes Maxillary buccal 27-g needle penetration (150)

5% Lidocaine 2 minutes Mandibular buccal 27-g needle penetration (73)

5% Lidocaine,

20% Benzocaine

3 minutes Maxillary buccal 27-g needle penetration (133)

20% Benzocaine 4 minutes Mandibular buccal 30-g needle penetration (116)

10% Lidocaine,

20% Lidocaine

15 minutes Maxillary and mandibular buccal 25-g needle penetration (67)

20% Lidocaine 15 minutes Maxillary and mandibular buccal 25-g needle penetration (20, 21)

20% Lidocaine 15 minutes Maxillary buccal Injection with 25–27-g needle (21)

60% Lidocaine 20 minutes Maxillary buccal Injection with 30-g needle (47)

65

Intraoral topical anesthesia

is the site of application and wider gauge needles

seem to be associated with greater failure of topical

anesthesia. Also most of the successful applications

had at least a 2-minute application. The exceptions

are the studies of Yaacob et al. (153), Carr & Horton

(20) and part of the investigation of Hutchins et al.

(76). The first of these studies (153) reported a 30-

second application of lidocaine to be effective in the

palate. The design of that investigation was not ideal

as the operator was not blinded and the active side

was injected first. It is known that the first of a pair of

injections is likely to be less painful (102) and thus

this would have contributed to the effect. Carr &

Horton (20) noted that a 30-second application of

benzocaine was better than placebo in the mandib-

ular mucosa but did not find that a similar regimen

was effective in the maxillary buccal sulcus; a later

study (21), which doubled the application time to

1 minute, failed to produce anesthesia better than

placebo in either arch. The study of Hutchins et al.

(76) investigated a number of methods of reducing

injection discomfort and part of their data suggested

that a 1-minute application of 20% benzocaine was

better than placebo in disguising injection pain in the

buccal sulcus, but not in the palate. These workers

injected less anesthetic than was used for the other

injection studies that showed a positive response (21,

47) and the authors were unsure of the clinical rele-

vance of their results. It seems therefore that appli-

cation times of at least 2 minutes are required before

needle penetration or injection. Indeed for an effect

on injection discomfort very long application times of

lidocaine (15–20 minutes) appear to be required. The

efficacies of different topical anesthetics are sum-

marized in Table 5 and show that some novel prep-

arations (EMLA, see below; and use of liposomes)

may be effective in reducing injection discomfort and

can be of use on the palate.

It is surprising that the gauge of needle affects the

efficacy of topical anesthetics as it has been reported

that needles of those gauges used in dentistry (25–

30 g) do not differ in the discomfort they produce

when inserted into oral mucosa (48).

EMLA

The above studies investigated topical anesthetics

designed for intraoral use. A number of investigators

have studied EMLA intraorally. EMLA is an acronym

for eutectic mixture of local anesthetics and is a 5%

mixture of prilocaine and lidocaine. This formulation

was developed in the late 1970s and early 1980s (81)

and has been used to anesthetize skin before a

number of procedures such as venepuncture and

minor operations (80, 101). It is one of the most

commonly used topical anesthetics in dermatological

practice (44). In dentistry it has been used on skin

before venepuncture for sedation and has been

reported as the sole means of anesthesia before

temporomandibular joint arthrocentesis (70). It is not

licensed for use intraorally but has shown interesting

properties when used in the mouth.

Table 5. Studies showing significant differences between different topical anesthetic agents in reducing needle pene-tration or local anesthetic injection discomfort. The lower agent of each pair in the left-hand column was more effective

Agents Duration Site Test Reference

20% Benzocaine,

1% Ropivacaine in liposomes

2 minutes Maxillary buccal 30-g needle insertion (42)

20% Benzocaine,

1% Ropivacaine in liposomes

2 minutes Maxillary buccal 30-g needle insertion (42)

5% Lidocaine

EMLA

5 minutes Periodontal ligament Intraligamentary injection

with 30-g needle

(110)

20% Benzocaine

EMLA

10 minutes Palate 27-g needle insertion (6)

10% Lidocaine,

20% Lidocaine

15 minutes Mandibular buccal 25-g needle insertion (67)

20% Benzocaine gel,

60% Lidocaine gel

20 minutes Maxillary buccal Maxillary infiltration

with 30-g needle

(47)

20% Benzocaine gel,

5% Amethocaine in liposomes

not reported Not reported Intraoral injection (155)

66

Meechan

Needle penetration studies

Holst & Evers (73) compared the effects of 2- and 5-

minute applications of 5% lidocaine and EMLA on

the penetration of a 30-g needle into the labial gin-

giva in the mandibular canine region and the palatal

mucosa opposite the upper canine in 10 healthy

female volunteers. These workers reported more pain

relief following the 5-minute compared with the 2-

minute application of the active agent. Both anes-

thetic regimens were more effective than placebo and

at 5 minutes EMLA was significantly better than 5%

lidocaine. In a further trial (73) these authors com-

pared the 2-minute application buccally of discs

impregnated with EMLA with application of placebo

discs to the lower first premolars. They reported that

pain related to penetration of a 27-gauge needle was

significantly reduced under the EMLA disc compared

with the placebo.

The effect of EMLA on the pain of palatal needle

penetration was also investigated in a double-blind

placebo-controlled study by Svennson & Petersen

(142). These authors used the application of orahe-

sive bandages for 5 minutes over the greater palatine

and incisive foramina and measured the pain of 27-

gauge needle penetration in volunteers using a visual

analogue scale. They found that the pain of needle

insertion was significantly reduced by EMLA but not

by placebo. This effect was more marked at the

greater palatine foramen compared with the incisive

foramen.

Al-Melh & Andersson (6) also looked at the effect of

EMLA in decreasing the discomfort of needle pene-

tration down to bone in the palatal gingiva adjacent

to the maxillary canine. They found that EMLA was

superior to 20% benzocaine in reducing discomfort

over a 10-minute application period. A double-blind

split-mouth investigation (150) compared the 2-

minute application of 5% lidocaine, 15% benzocaine

with 1.7% amethocaine, and EMLA on the discomfort

produced by insertion of a 27-gauge needle to a

depth of 5 mm in the maxillary premolar buccal

sulcus. Volunteers reported significantly less pain

with all active agents compared with placebo and the

authors concluded that EMLA was the most effective

of the topical preparations. Franz-Montan et al. (42)

compared 2-minute applications of EMLA with

similar applications of 20% benzocaine, 1% plain

ropivacaine, and 1% ropivacaine in liposomes in

disguising 30-g needle penetration down to the

periosteum in the maxillary canine gingiva. EMLA

was similar to the other materials on the visual

analogue scale scores reported for penetration but,

together with the encapsulated ropivacaine, provided

longer-lasting soft tissue anesthesia.

Injection studies

Meechan & Donaldson (108) investigated the effects

of a 5-minute application of 5% lidocaine and EMLA

in reducing the discomfort of maxillary infiltration

injections in children. They found no difference in

injection discomfort between treatments. Nayak &

Sudha (117) studied the effects of a 3-minute appli-

cation of EMLA to 2-minute applications of 18%

benzocaine or 5% lidocaine before buccal infiltration

anesthesia of lidocaine with epinephrine with a

26-gauge needle in children in a double-blind, split-

mouth investigation. Using visual analogue scores for

injection discomfort they reported that EMLA was

significantly better in reducing injection discomfort

than the other agents. A third study (125) with 40

children compared a 5-minute application of EMLA

with a 2-minute application of 20% benzocaine in

reducing the palatal injection when a 27-gauge nee-

dle was used. The results showed that there was no

difference in visual analogue scores for pain response

during injection between treatments.

The results of a study (111) that compared the

5-minute application of EMLA with placebo or

transcutaneous electrical nerve stimulation (TENS) to

palatal mucosa in adult patients about to have max-

illary dental extractions showed that EMLA was sig-

nificantly more effective than the other treatments in

reducing the discomfort of palatal injections of 2%

lidocaine with 1:80,000 epinephrine with 27-gauge

needles.

There has been one randomized double-blind

split-mouth study (110) that compared the efficacy of

EMLA and 5% lidocaine applied for 5 minutes in the

gingival crevice as a means of reducing the discom-

fort of intraligamentary injections of 2% lidocaine

with 1:80,000 epinephrine. The results of that study

showed that EMLA was more effective than lidocaine

alone in reducing the discomfort of this method of

anesthesia

When looking at Table 6, which summarizes the

results of the studies that have compared EMLA to

placebo before intraoral needle penetration or

injection it is apparent that this material appears to

be effective on the palate. This is useful because this

is an area considered difficult to anesthetize with

topical anesthetics because of the high degree of

keratinization that might make diffusion difficult.

67

Intraoral topical anesthesia

Use of topical agents to provideanesthesia for intraoralprocedures

The use of topical application to obtain anesthesia for

intraoral operative procedures is appealing. There are

obvious advantages to the patient. Many patients fear

dental injections (113). Extensive postoperative

numbness may also be troublesome after injection

(147). Indeed, patients may accept a less effective

form of anesthesia if it means injections can be

avoided (103). In addition, such a technique could

benefit the dental team because it should reduce the

incidence of needle-stick injuries.

Topical application of anesthetic agents to obtain

anesthesia of the dental pulp has been investigated

but is not in routine use (see below). It would appear

that topical application might be more successful in

obtaining anesthesia of the soft tissues intraorally. A

number of experimental and clinical studies have

looked at the use of topical anesthetics as the sole

means for anesthesia of the intraoral soft tissues.

Some agents are better than others in this regard.

Conventional intraoral agents

Experimental

The use of a patch containing 50 mg lidocaine for

30 minutes to obtain local anesthesia of the lips and

attached gingivae was investigated by Brook et al.

(15). Perception to painful stimuli (sharp probing) was

eliminated in a mean time of 7.4 minutes after use of

the patch. Normal sensation returned in a mean time

of 26.4 minutes following patch removal. There was

some loss of sensation on the vermilion border and

skin surfaces, normal sensation returning to these

areas in a mean time of 22.6 minutes following patch

removal. A symptomless whitening of the mucosa in

the area of application was noted at 24 hours in two

volunteers. This disappeared after 48 hours.

Clinical

Carr & Horton (20) compared the efficacies of a 20%

lidocaine bioadhesive patch and 20% benzocaine

gel in reducing the discomfort of scaling and root

planing in two randomized double-blind placebo-

controlled trials, each with 20 patients. The site of

application was the buccal attached gingiva in the

bicuspid-molar area of each jaw. The patch was

applied for 15 minutes and the gel for 30 seconds. The

lidocaine patch reduced the discomfort of scaling and

root planing when compared with placebo (mean

change 22.9 mm on visual analogue scale) whereas

the benzocaine gel did not differ from placebo (mean

difference – 1.3 mm on visual analogue scale). When

the different jaws were compared the lidocaine patch

was more effective than the benzocaine gel in the

maxilla (mean difference of 16.4 mm on visual ana-

logue scale) but not in the mandible (mean difference

of 8.2 mm on visual analogue scale). In another study

of similar design (only differing in that the time of

application of benzocaine was increased to 1 minute)

these workers (21) confirmed their previous findings

that the lidocaine patch was superior to placebo in

reducing the discomfort of scaling and root planing

but that benzocaine did not differ significantly from

placebo in this regard.

The use of topical anesthesia as the sole means of

pain control for removal of intraoral soft tissue has

been reported. One investigation (131) compared the

5-minute topical application of a strip containing

20 mg lidocaine with the injection of plain 2% lido-

caine for oral mucosal punch biopsies (approxi-

mately 4 mm deep) in an unblinded study with 20

subjects. The results of that study showed that both

treatments produced similar anesthetic duration but

that biopsies performed under the film were recorded

as being significantly more painful. The discomfort

after the topical application was not associated with

the initial punch cut, but with the incision at the

base of the biopsy, probably as a result of poor

penetration.

Table 6. Studies showing positive effects of EMLA over placebo in reducing needle penetration or local anestheticinjection discomfort

Agent Duration Site Test Reference

EMLA 2 minutes Maxillary buccal 27-g needle penetration (148)

EMLA 5 minutes Palate and mandibular buccal 27-g needle penetration (73)

EMLA 5 minutes Palate 27-g needle penetration (142)

EMLA 5 minutes Palate Injection with 27-g needle (111)

68

Meechan

One study (139) compared the 5-minute applica-

tion of a patch containing 20% lidocaine with the

1-minute application of 20% benzocaine gel before

application of rubber dams in children aged

6–17 years using an unblinded split-mouth design.

These workers found no difference in efficacy

between treatments but concluded that the patch

was not suitable for children because of the lack of

adhesion and the length of time of application. In

that study, patch adhesion was <30% but was age-

related, especially for girls where the increase in

adhesion was 9 percentage points per year of age.

EMLA

Experimental

Svensson et al. (141) used argon laser stimulation of

the lower labial gingiva to compare the efficacy and

duration of effect of lidocaine and EMLA. They

measured pain and sensory thresholds following a

2-minute application of 2% lidocaine gel and 2-, 5-

and 15-minute applications of 1 g EMLA. The latter

formulation was significantly more effective than

lidocaine alone in increasing sensory and pain

thresholds. The greatest increase in pain threshold

was noted immediately after removal of the topical

anesthetic for all treatments. Sensory and pain

thresholds were elevated for all regimens up to

25 minutes after removal. The duration of EMLA

application did not affect the intensity of the anes-

thetic effect on the gingiva. The authors concluded

that a 2-minute application on the gingiva produced

analgesia for 10 minutes.

Contrary to the results described above, Haasio

et al. (60) found no difference in the analgesic effects

of EMLA and lidocaine on buccal gingival mucosa on

the upper jaw in 10 volunteers. They recorded both

sensory and pain thresholds using electrical stimu-

lation. The application and amounts of anesthetic

differed between this trial and that described above

(141). In this study, 4 g of EMLA was applied over

four sites on the buccal gingiva with a toothbrush and

the lidocaine formulation was a 10% spray, which

was applied to four sites on the upper gingivae (total

200 mg lidocaine). The maximum analgesic effect

occurred at a mean time of 13 minutes for EMLA and

at 14 minutes for lidocaine. Normal sensation had

returned in most cases by 30 minutes for each

treatment.

Nayak & Sudha (117) looked at the anesthetic onset

times of EMLA, 18% benzocaine, and 5% lidocaine in

providing anesthesia to blunt probing of the maxil-

lary anterior gingiva in children. They reported that

the mean onset times were 75 seconds for benzo-

caine, 105 seconds for lidocaine, and 138 seconds for

EMLA. McMillan et al. (106) compared the effects on

the pain-pressure threshold (105) and sensitivity to

pin-pricking of EMLA and 5% lidocaine applied

topically on the buccal attached gingiva in the

maxillary premolar region for 10 minutes. The pain–

pressure threshold was measured using an algometer

with a 4-mm ball-ended tip (106). EMLA was superior

to 5% lidocaine in increasing the pain–pressure

threshold and in producing anesthesia to pin-prick.

The effects on pain–pressure threshold suggested

that EMLA was superior to lidocaine in penetrating

the buccal cortical bone. EMLA produced anesthesia

to pin-prick in all 10 volunteers in that trial but

lidocaine was successful in only eight.

Roghani et al. (130) also looked at the effects of

topical anesthetics on the load required on the gin-

giva to produce discomfort in a double-blind study

that compared placebo, 1% dyclonine, 10% cocaine

20% benzocaine, 10% lidocaine, and EMLA on the

maxillary anterior gingiva. These workers used a

1–8 mm ball-ended tip connected to a measuring

device and reported that a 3-minute application of

EMLA was more effective than the other topical

agents and placebo in raising the pain–pressure

threshold. In the study of Franz-Montana et al. (42),

the median duration of gingival anesthesia provided

after a 2-minute application of EMLA in 30 volunteers

was around 14 minutes.

The results presented above suggested that EMLA

might be useful as a topical anesthetic for minor

operative procedures on the gingiva and it has been

investigated in this regard in the clinical studies

described below.

Clinical

The effects on the discomfort of scaling of 5-minute

applications of EMLA or placebo to the gingival

margins in patients with mild chronic periodontitis

have been compared in a double-blind, randomized,

split-mouth study (143). EMLA reduced the pain and

unpleasantness of scaling in both jaws when com-

pared to placebo. The influence on pain was more

marked than the effect on unpleasantness. In another

double-blind, split-mouth volunteer study (36) a 5-

minute application of EMLA allowed a significantly

greater depth of pain-free probe penetration into the

gingival crevice compared to similar treatment with

5% lidocaine. The use of a 4-minute application of

4 g EMLA to the gingivae using a toothbrush as a

means of pain control for the removal of arch-bars

69

Intraoral topical anesthesia

used in intermaxillary fixation was investigated in a

double-blind, placebo-controlled trial in 45 dentate

patients (123). Pin-prick sensation was significantly

reduced in the EMLA group 5 minutes after tooth

brushing with the topical compared to the placebo,

before removal of the arch-bars. Following removal of

the arch-bars (mean time 19 minutes after tooth

brushing) there was no difference between treat-

ments in response to pin-pricking of the gingiva.

Significantly more patients with EMLA reported no

pain compared to those who received placebo during

removal of the arch-bars.

There is a case report (107) of the use of a 15-

minute application of EMLA as the only means of

pain control for the surgical removal of intraoral soft

tissue from the palate in a patient with a needle

phobia.

Oraqix�

Those studies discussed above, which showed that

EMLA was superior to 5% lidocaine, led to the

development of a topical preparation of lidocaine

and prilocaine dedicated for intraoral use. This

material, known as Oraqix�, is supplied as a

thermosetting agent. Oraqix contains 25 mg ⁄ g

lidocaine and 25 mg ⁄ g prilocaine. The material is

liquid at room temperature but when injected into

the gingival crevice it forms an elastic gel (46).

Interestingly, although Oraqix was specifically for-

mulated for intraoral use, subjects who have re-

ceived both Oraqix and EMLA in the mouth have

reported that the latter was superior with regard to

taste and smell (6).

Oraqix has been investigated as a means of

reducing the discomfort of intraoral injections (6),

where it has been shown to be more effective than

20% benzocaine gel in reducing the pain of palatal

infiltrations in a human volunteer study. The indi-

cation for the use of Oraqix however, is for the relief

of discomfort during periodontal treatments. It has

been evaluated in a number of studies as the sole

agent for anesthesia during periodontal treatments

(35, 46, 78, 96, 147). When applied to periodontal

pockets, onset of action is rapid with an anesthetic

effect obvious at 30 seconds (46). An open-label

investigation into the efficacy of Oraqix in reducing

the discomfort of scaling and root planing in 30

patients showed that pain reduction (as measured by

a visual analogue scale) was significantly greater after

a 30-second compared with a 2-minute application of

the gel, although there was no difference between a

30-second and a 5-minute application (46). There

was no difference reported in duration of anes-

thesia to probing between 30-second, 2-minute

and 5-minute applications (mean duration was

18–20 minutes); however, the authors of that study

noted that this does not reflect anesthesia for scaling

or root planing.

A placebo-controlled study with 130 patients (35)

looked at the discomfort of periodontal debride-

ment after a 30-second application of Oraqix into

periodontal pockets. In that investigation, median

pain scores measured by visual analogue scale were

low but those recorded after active treatment were

significantly lower than placebo (5 and 13 mm

respectively). Verbal rating scores using a five-point

scale did not differ between treatments in that study;

78% reporting no or mild pain with active treatment

and 76% with placebo. Another investigation (78)

used a similar design to that described above (35) but

varied the application time of Oraqix between

30 seconds and 2 minutes. Significant differences

were apparent in visual analogue scale scores be-

tween placebo and active treatment and in this study.

Differences in the five-point verbal rating score were

also apparent with 90% of patients in the active

group and 64% in the placebo group reporting no or

mild pain. Rescue anesthesia was required by 11% of

the active and 17% of the placebo groups. No data

correlating the time of application and efficacy were

reported. The data from this study suggested that the

effect of Oraqix was more pronounced in subjects

with more severe periodontal disease. Following on

from that finding, another study (96) looked at the

effect of Oraqix in patients who reported moderate to

severe pain on periodontal probing (i.e. >30 mm on

a visual analogue scale [27]). In this study with 85

patients Oraqix was placed in the periodontal pocket

for 30–45 seconds. The results showed that visual

analogue scale scores and verbal rating scores were

less when the active treatment was compared to

placebo; 70% of those receiving Oraqix reporting no

or mild pain after scaling and root planing, compared

with 48% for placebo. None of the 43 patients in the

Oraqix group reported severe pain whereas four of 42

patients in the placebo group reported severe or very

severe pain. Five per cent of the active and 17% of the

placebo patients required rescue anesthesia. Unlike

the previous study, the results of this investigation

did not show any relationship between the extent

of disease and the efficacy of Oraqix. The data from

the three double-blind placebo-controlled studies

described above (35, 78, 96) were pooled and

re-analysed by considering percentage changes

between active and placebo treatments (97) and the

70

Meechan

authors concluded that the active treatments reduced

discomfort during scaling and root planing by a

factor of 50%.

One open labeled, cross-over, multi-center study

of 170 subjects investigated patients� responses to

Oraqix and conventional infiltration anesthesia for

scaling and root planning (147). Evaluations were

performed immediately following and 4 hours after

treatment. Efficacy of anesthesia, as determined by

both operator and patient, was greater follow-

ing injection compared to application of the gel;

however, the majority of patients (70%) preferred

anesthesia with Oraqix. This was despite the fact that

one in five patients did not receive adequate pain

control after application of the gel. The principal

reason for the preference was less numbness after

treatment; 63% of subjects were bothered to a sig-

nificant degree by the postoperative feeling after the

injection compared to 44% after Oraqix. The main

reason chosen by those preferring injection (22%)

was greater comfort during treatment. In none of

these studies (35, 46, 78, 96) were there differences in

adverse effects between active and placebo treat-

ments and those reported could have been caused by

the operative treatments provided.

An interesting finding with Oraqix is the report

that onset of anesthesia is rapid and seems to diminish

very quickly. There is evidence that a 30-second

application is more effective than a 2-minute treat-

ment (46). This is in contrast to the other work

described above, which has shown that the efficacy of

intraoral topical anesthesia increases with time of

application (67). This could be the result of �wash away�and might vary between methods of application, for

example if a patch is used loss of active agent into the

mouth (rather than into the tissues) may be reduced.

When performing procedures such as scaling it is

useful to have anesthesia of the tooth as well as the

soft tissues. It is thus valid to ask the question – do

topical local anesthetics produce pulpal anesthesia?

This is addressed below.

Studies into use of topical anesthetics toprovide anesthesia for procedures onteeth

A number of workers have investigated changes in

pulpal response to electrical testing after the appli-

cation of topical anesthetics.

Conventional agents

Brook et al. (15) reported that the 30-minute appli-

cation of a patch containing 50 mg lidocaine to the

attached gingiva in the maxillary premolar region

produced significant elevations in pain threshold

compared to base-line in first premolars and when

compared to those teeth adjacent to placebo patches.

No teeth in either the test or control group showed

total anesthesia. Franz-Montan et al. (42) showed

that a 2-minute treatment of 20% benzocaine or 1%

ropivacaine (plain and in liposomes) to the maxillary

buccal gingiva in the canine region in human vol-

unteers did not alter canine pulp responses during

the 20 minutes following application. The application

of a drop of 50% lidocaine solution onto exposed

human dentin reduced the response to air blasting

and probing in an uncontrolled study with six vol-

unteers (7), while an anecdotal report (33) claimed

great success when 20% benzocaine was used as a

topical application to the dental pulp during endo-

dontic treatment.

The application of patches containing 20 mg lido-

caine to the buccal and palatal ⁄ lingual gingiva has

been investigated as a means of pain control for

dental extractions (144). Both children and adults

were included in this study of 49 extractions in 40

patients. The extraction was performed when the

gingivae could be detached from the tooth without

pain. The mean times to extraction were app-

roximately 19 and 13 minutes for the maxilla and

mandible respectively. Successful anesthesia was

achieved in 81% of teeth. Gangarosa (49) used ion-

tophoresis for 10 minutes to apply 2% lidocaine with

1:50,000 epinephrine for the extraction of deciduous

teeth. The method was successful in 12 out of 13

teeth, which were extracted without discomfort.

EMLA

The effectiveness of a 5-minute application over the

apical areas of maxillary deciduous teeth has been

investigated in a double-blind placebo-controlled

trial (108). The results showed no difference in

response to electrical pulp testing between treat-

ments. The same investigators studied the efficacy of

EMLA to eliminate the discomfort of restorative

dentistry on deciduous teeth. They found that 80% of

the children studied required supplementary local

anesthesia to allow treatment to be completed pain-

lessly (108). Another investigation (151) compared the

application of EMLA, 10% lidocaine, and placebo on

the response of maxillary central incisors to electrical

pulp testing. Twelve of the 13 volunteers who received

EMLA showed no response to electrical pulp testing

between 15 and 30 minutes of application; however,

some of the lidocaine-treated and placebo-treated

cases also showed failure to respond under maximum

71

Intraoral topical anesthesia

stimulation from the pulp tester. Another human

volunteer study (42) showed that the 2-minute

application of EMLA to the maxillary buccal gingiva in

the canine region did not affect canine pulp responses

during the 20 minutes after placement.

The effectiveness of 1 g topical EMLA as an alter-

native to infiltration anesthesia as pain control for

restorative procedures was investigated in an

uncontrolled pilot study in 12 patients (149). The

authors reported that 75% of subjects obtained

adequate analgesia. They concluded that this method

provided some, but not complete, anesthesia to allow

restorative dentistry to be performed.

Topical anesthetic relief of toothacheand post-operative pain

The earliest reference to local anesthetic action of

cocoa leaves was an intraoral effect recorded in 1653

when Bernabe Cobo reported that chewing cocoa

leaves eased the pain of toothache (18). This may or

may not have been a topical effect. Over-the-counter

medications containing topical anesthetics such as

benzocaine have been available for over 80 years.

More recent studies have investigated the use of

topically applied anesthetics for the symptomatic

treatment of toothache (51, 66, 68, 140). It has been

pointed out that significant soft tissue anesthesia

(including periosteum) may influence the relief of

toothache and that penetration through to bone and

to the pulpal supply is not essential to produce some

relief, as a result of convergence of trigeminal fibers

at the brainstem (66).

Sveen et al. (140) noted that a 7.5% benzocaine gel

produced better pain relief than placebo when

applied to the gingivae adjacent to painful teeth in a

double-blind trial with 49 patients. Pain relief

occurred within 3–4 minutes. The treatment was not

entirely successful, with 83% of the active treatments

producing relief. A similar study investigated higher

concentrations of benzocaine in gels (10% and 20%)

and found these to be better than placebo in

decreasing the intensity of toothache (51). Hersh

et al. (66) also used benzocaine but this time

included in an adhesive patch (12 mg benzocaine) as

opposed to a gel. They investigated the efficacy of this

patch in a double-blind, placebo-controlled trial in 60

patients with toothache. Patches were applied at the

mucogingival junction of the affected tooth and

remained in place for an hour. These workers

reported a large placebo response in this investiga-

tion and although the active patch was superior in all

their outcome measures (pain intensity and pain

relief scores) the only significant difference they

noted was an increase in the percentage of patients

with meaningful pain relief at 30 minutes with the

benzocaine patch. The median time to first notice-

able pain relief with the active patch was between 5

and 6 minutes. In a later study, these workers (68)

reported a greater number of responders (that is

patients who reported a significant pain reduction)

following the application of 20% benzocaine gel

compared to placebo for the treatment of toothache.

The median onset for meaningful pain relief was

8.3 minutes.

Three investigations (8, 52, 57) have looked at the

use of topical bupivacaine as a means of reduc-

ing post-operative discomfort in children following

dental extractions. In one study (57) dental rolls

soaked with 7 ml of 0.25% bupivacaine with

1:200,000 epinephrine placed over the extraction sites

were more effective than saline-soaked rolls in

relieving discomfort following extractions under

general anesthesia in children aged between 7 and

15 years. The swabs were placed after the children

awoke from the general anesthetic. The other two

studies (8, 52) showed that no difference in pain relief

was obtained when swabs with 0.25% bupivacaine

and epinephrine or placebo (saline or distilled water)

were inserted over the extraction sites in children

immediately following extractions, while the child

was still anesthetized. The mean time of application

of the agent was 8 minutes in the former study (8).

Plasma levels following intraoral topicalanesthetic application

Anesthetic applied topically is absorbed and will

eventually enter the bloodstream. This is important

because improper use could lead to toxicity, either as

a result of topical application alone or in combina-

tion with any injected anesthetic (see above). It has

been claimed that toxic reactions are more common

after topical application compared to other methods

of local anesthetic delivery (3). When considering

toxic reactions the amount of drug is important. The

concentration of drug in topical preparations is

greater than that used for injectable formulations. An

animal study (3) demonstrated that entry of local

anesthetics into the circulation was quicker after

topical administration to the pharynx compared to

subcutaneous injection. Topical administration

achieved much higher peak levels than slow intra-

venous infusion of the same dose. The authors of that

study concluded that, although the peak plasma level

was around a third of that obtained after intravenous

72

Meechan

injection, the profile of entry into the bloodstream

following topical administration simulated that after

rapid intravenous injection. Certainly toxic reactions,

including fatalities, to topically applied local anes-

thetics have occurred (3, 77).

Lidocaine

Hersh et al. (67) found that plasma lidocaine levels

rose steadily after the use of patches containing

either 10 or 20 mg of the local anesthetic during the

15 minutes of patch application and then remained

steady over a period of 30 minutes from the

15-minute sample. The average peak plasma levels

obtained were 0.016 lg ⁄ ml for the 10% patch and

0.022 lg ⁄ ml for the 20% patch. These levels are an

order of magnitude less than those achieved after the

intraoral injection of 2% lidocaine solutions (19, 56).

Brook et al. (15) reported peak lidocaine levels

45–60 minutes after a 30-minute application of a

patch containing 50 mg lidocaine on the buccal

gingivae opposite the premolar teeth in either jaw.

The mean peak level was around 0.030 lg ⁄ ml and

the highest concentration recorded was 0.095 lg ⁄ ml.

Haasio et al. (60) reported a mean plasma level

0.35 lg ⁄ ml for lidocaine 30 minutes after the in-

traoral delivery of a large dose (200 mg) of lidocaine

as a 10% lidocaine spray. The highest concentration

noted was 0.66 lg ⁄ ml at 20 minutes.

Leopold et al. (94) investigated lidocaine levels in

children after the intraoral application of patches

containing 20% lidocaine. A 5-minute application

in the maxillary buccal gingiva was used. The

maximum level of lidocaine recorded in plasma

was 0.128 lg ⁄ ml (mean 0.082 lg ⁄ ml). The average

time to peak plasma concentration was 9 minutes

with a range of 1–15 minutes. These workers point

out that although these levels are well below the

toxic concentration they are around four times

higher than those reported with the same material

in adults (0.022 lg ⁄ ml see study of Hersh et al. [67]

above).

EMLA

Plasma levels of lidocaine and prilocaine have been

investigated after the 4-minute application of 4 g

EMLA (100 mg lidocaine and 100 mg prilocaine) with

a toothbrush to the gingiva (60, 123). Pere et al. (123)

reported that the highest plasma level for lidocaine

was 0.26 lg ⁄ ml at 15 minutes and for prilocaine it

was 0.09 lg ⁄ ml at 30 minutes after the start of the

application. The plasma levels of lidocaine were

greater than those of prilocaine because of the more

rapid metabolism of the latter. Haasio et al. (60)

found that the highest lidocaine concentration was

0.47 lg ⁄ ml at 5 minutes and the highest prilocaine

concentration was 0.21 lg ⁄ ml at 10 minutes follow-

ing the application of 4 g EMLA intraorally. These

authors noted that absorption was more rapid after

EMLA compared to a 10% lidocaine spray, but the

only significant difference was a higher mean plasma

concentration of lidocaine at 30 minutes in the 10%

lidocaine spray group where the mean plasma lido-

caine concentration was 0.35 lg ⁄ ml compared with

0.14 lg ⁄ ml in the EMLA group. The highest lidocaine

concentration in the EMLA group was 0.47 lg ⁄ ml at

5 minutes compared to 0.66 lg ⁄ ml in the lidocaine

group at 20 minutes.

The plasma concentrations of lidocaine and prilo-

caine following the 30-minute application of 8 g of

EMLA to the buccal mucosa were measured in 12

volunteers by Vickers et al. (149). Peak plasma levels

occurred 40 minutes after initial application for both

anesthetics; the mean peak level for lidocaine was

0.221 lg ⁄ ml and for prilocaine was 0.131 lg ⁄ ml. The

maximum concentrations noted in any one subject

were 0.418 lg ⁄ ml (lidocaine) and 0.223 lg ⁄ ml

(prilocaine).

Oraqix�

Plasma levels of lidocaine and prilocaine following

application of Oraqix� have been reported in two

studies. In one study (45), doses of 0.9–3.5 g Oraqix

were applied to periodontal pockets in 10 patients.

Blood samples were taken 10, 20, 30, 40, 60, 75, and

90 minutes after application of Oraqix. Peak plasma

levels occurred between 20 and 40 minutes after

application. The highest concentration of lidocaine

reported was 0.266 lg ⁄ ml (at 40 minutes) with a

median of 0.169 lg ⁄ ml (at 30 minutes). The great-

est plasma level of prilocaine was 0.118 lg ⁄ ml

(at 30 minutes) with a median of 0.077 lg ⁄ ml

(at 30 minutes). In another study (65), plasma levels

of lidocaine and prilocaine were measured following

longer applications of a larger dose of Oraqix. In this

study a median of 8.6 g (maximum 8.7 g) of Oraqix

was applied over periods up to 3.4 hours and blood

samples were taken in a 10-hour period post-appli-

cation. Peak plasma levels of the anesthetics were

achieved 3.7 hours after the start of application for

lidocaine and 3.3 hours for prilocaine. The greatest

level of lidocaine was 0.55 lg ⁄ ml and of prilocaine

was 0.18 lg ⁄ ml. Methemoglobin levels were mea-

sured in this study; the greatest level noted was

1.73% with a median of 1.23%, occurring 1–4 hours

after application. This represented a rise from the

73

Intraoral topical anesthesia

pre-application median of 0.77% but was still within

normal limits (<2%).

Table 7 summarizes the results of the studies that

have measured plasma levels of anesthetics following

intraoral topical application and also shows the

results obtained in one study (56) that investigated

plasma levels of anesthetics after buccal infiltration

anesthesia. It can be seen from Table 7 that, although

conventional intraoral topical agents produce levels

of anesthetic in plasma that are an order of magni-

tude below those obtained after injection, large doses

of some topical anesthetics achieve plasma levels

similar to those obtained after conventional buccal

infiltration. It is therefore essential when considering

maximum doses that both topical and any injected

material are considered.

Adverse effects of topicalanesthetics

The topical application of anesthetics seems to

produce few problems locally. The problems of

allergy, especially with ester-type local anesthetics,

were mentioned earlier and must always be borne in

mind, especially as the ester benzocaine is a popular

topical agent. Non-ester agents, such as dyclonine,

have also been reported to produce allergies after

topical use in the oro-facial region (126). Neverthe-

less, reports of damage to mucosa are not common

and any adverse effects appear to be reversible (67).

An exception is the misuse of the anesthetic agent

cocaine. This drug can cause ulceration and gingival

necrosis following topical application as a result of

vasoconstriction (121, 128). A histological study in

hamsters showed that the application of 5% lido-

caine for periods up to 24 hours to the oral mucosa

revealed no signs of any inflammatory response or

tissue edema (22) while in humans, the application

of 10% or 20% lidocaine patches did not differ from

the use of placebo patches with regard to adverse

effects on the mucosa (67). There were no adverse

local effects reported following a 30-minute appli-

cation of 8 g EMLA to buccal mucosa in humans

(149).

Pashley & Parsons (122) described a case of severe

pain following application of 5% lidocaine ointment

adjacent to teeth with exposed dentine. They sug-

gested that this was the result of an osmotic effect on

dentinal tubules caused by the hypertonic topical

preparation.

It was mentioned above that one of the adverse

effects of some local anesthetics is methemoglobi-

nemia and that the drugs most likely to cause this

Table 7. Results of studies measuring plasma levels of anesthetic agents following topical intraoral and buccalinfiltration administration

Dose of anesthetic [formulation] Average (maximum) peak plasma level (lg ⁄ ml) Reference

23 mg Lidocaine [10% patch] 0.016 (67)

46 mg Lidocaine [20% patch] 0.022 (67)

46 mg Lidocaine [20% patch]* 0.082 (0.128)* (94*)

50 mg Lidocaine [patch] 0.03 (0.095) (15)

200 mg Lidocaine [10% spray] 0.35 (0.66) (60)

4 g EMLA Lidocaine 0.21 (0.26), Prilocaine 0.05 (0.09) (123)

4 g EMLA Lidocaine 0.18 (0.47), Prilocaine 0.1 (0.21) (60)

8 g EMLA Lidocaine 0.22 (0.42), Prilocaine 0.13 (0.22) (149)

Up to 3.5 g Oraqix� Lidocaine 0.169 (0.266), Prilocaine 0.077 (0.118) (45)

8.6 g Oraqix� Lidocaine 0.28 (0.55), Prilocaine 0.11 (0.18) (65)

36 mg Lidocaine [2% Lidocaine

as a buccal infiltration]

0.31 (56)

36 mg Lidocaine [2% Lidocaine

with 1:100,000 epinephrine

as a buccal infiltration]

0.22 (56)

*A study in children.

74

Meechan

problem are benzocaine and prilocaine. There are

over 100 case reports of benzocaine-associated

methemoglobinemia, mainly associated with the

20% benzocaine spray (148), especially in the phar-

ynx (1, 129). It has been reported that the estimated

incidence of methemoglobinemia following topical

application before bronchoscopy is 1:7000 (62). It

should be pointed out that the doses used on the

pharynx are greater than would be applied topically

in the mouth, but the fact that methemoglobinemia

does occur must be remembered and there are two

case reports of methemoglobinemia following topical

use of benzocaine in the mouth (39).

There has been a case of methemoglobinemia

reported following the use of 5 g EMLA in a 12-

week-old child (76). The methemoglobin level was

28%. In that case the child was also receiving a

sulfonamide, which can also produce methemoglo-

binemia. Normally the application of up to 5 g EMLA

to the skin of young children <6 years does not raise

methemoglobin levels above safe limits (43).

Conclusions

This paper has looked at the intraoral use of topical

anesthesia. The conclusions that can be drawn from

the studies reported are that topical anesthetics do

have a pharmacological effect when used on oral

mucosa, and that some formulations are better than

others. When used properly they can be expected to

reduce the discomfort of needle penetration before

local anesthetic injection; however, the discomfort

of anesthetic injection may not be so well disguised

with conventional intraoral topical anesthetics and

other methods such as slow injection speed should

be used. There is evidence that some soft tissue

procedures can be performed more comfortably

following the use of topical anesthetics; however,

pulpal anesthesia is not yet guaranteed by this

method.

When used sensibly adverse effects are few and

not serious. Plasma levels are within safe limits;

however, the amount of topical anesthetic used must

be considered when supplementing with conven-

tional local anesthesia, particularly in children.

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