I N V I T E D R E V I E W
Local anaesthesia
J.G. Meechan
School of Dental Sciences, Newcastle University, Newcastle-upon-Tyne, UK
Abstract
This article describes current concepts in the mechanism of action of local anaesthetic drugs and discusses recent advances in the equipment and drugs that may be used to provide intra-oral anaesthesia.
Key words:
articaine, levobupivicaine, lidocaine, local anaesthesia, regional block, syringes
Correspondence to:
Dr JG Meechan School of Dental Sciences Newcastle University Newcastle NE2 4BW UK
Tel.:+44 191 222 8292 Fax:+44 191 222 6137 email: J.G.Meechan@ncl.ac.uk
Accepted: 23 October 2007 doi:10.1111/j.1752-248x.2007.00003.x
Introduction
Excellent pain control is an essential part of surgical practice. Local anaesthesia is the mainstay of pain control for outpatient oral surgery procedures. The anaesthetic effects of cocaine were discovered by Albert Niemann in the 1850s1. Since that time a number of advances have occurred in relation to local anaesthetic drugs and delivery systems.
This article will consider current concepts in the action of local anaesthetics and recent developments in drugs and the way they are delivered.
Current understanding of the mode of action of local anaesthetic drugs
There are two theories proposed for the action of local anaesthetics. These are the membrane expansion theory and the specific binding theory. The former is a non-specific mechanism that occurs by swelling of the nerve cell membrane as the lipophilic local anaesthetic is absorbed into the membrane. This perturbation influences the configuration of the sodium channel and inhibits entry of sodium into the cell, which pre- vents nerve cell depolarisation and thus firing.
Although this mechanism may play some role in the
action of local anaesthetic drugs, it is now accepted that the specific binding theory2is a more accurate expla- nation of the mechanism of action of local anaesthetics.
The evidence to support this theory is strong. Different isomers of the same drug show different local anaes- thetic activity3 – a feature that cannot be readily explained by the non-specific membrane expansion theory. In order to understand the specific binding theory of local anaesthetic action, it is necessary to understand the structure of the voltage-gated sodium channel, which is the site of local anaesthetic action.
The sodium channel has been well characterised and critical areas that affect local anaesthetic binding have been identified4,5. Indeed nine different types of sodium channels have so far been identified6. These different sodium channels are not all equally susceptible to the action of local anaesthetics and could explain why certain conditions such as inflammation, which might lead to the development of altered channels, can lead to failure of local anaesthesia7. The basic structure of the sodium channel consists of three subunits known asa, b1andb2. The pore through which sodium enters the cell is contained in thea subunit; the b components are concerned with intercellular interactions and regula- tion of channel gating4. Thea unit is composed of four very similar zones named domains I–IV. Each of these
domains contains six protein helical segments anno- tated S1–S6. These segments vary in their structure;
segments S1, S2 and S3 are all negatively charged and S4 is positively charged3. Figure 1 is a diagrammatic representation of the alignment of thea unit at differ- ent stages of the nerve firing cycle and the effect of local anaesthetic binding. At rest the S4 segments are present in the channel of the pore and act as an obstruction to sodium entry (Fig. 1a). Depolarisation and entry of sodium into the cell is achieved by the S4 segments twisting into the body of thea unit (Fig. 1b) – an action known as the sliding helix. During the refractory period of the firing cycle a protein loop between domains III and IV extends into the channel preventing further entry of sodium4 (Fig. 1c). Local anaesthetics block sodium entry by maintaining this loop in the position it occupies during the refractory period (Fig. 1d). Two amino acids have been identified on the S6 segment of domain IV (Phe 1764 and Tyr 1771) that are critical for local anaesthetic binding4. Access to the local anaesthetic binding site is most readily achieved when the nerve cell is in the inacti- vated conformation3,7. It has been claimed that local anaesthetic binding is 17 times lower for resting com- pared with inactivated channels3. The more frequently
a nerve fires the more times it enters the inactivated configuration. This means that rapidly firing neurones are the most susceptible to the effects of local anaes- thetics, which explains the phenomenon known as use- (or frequency-) dependent block. The fact that specific drug binding sites are now being identified8is exciting as this means that local anaesthetic agents with greater specificity for specific sodium channels could be developed. This could lead to the development of agents that are less cardiotoxic as well as those that may perform better in the presence of inflammation. In addition, there is a greater understanding of the het- erogeneity of adrenergic receptors9,10; this could lead to the development of site-specific vasoconstrictors, which might further reduce the unwanted effects of local anaesthetics.
Recent advances in intra-oral local anaesthesia
A number of developments have occurred over the last decade both in relation to the drugs used for local ana- esthesia and in relation to the equipment used to deliver these drugs. Changes in delivery systems have
I II I I
IV III
Na
+I II I I
IV III
I II I I
IV III
I II I I
IV III
la
(a) (b)
(c) (d)
Figure 1 The a subunit of the sodium channel. The channel is comprised of four domains (I–IV), each of which contains six helical segments. Segments S1–S3 (brown) are negatively charged and segment S4 (red) is positively charged. (a) The nerve cell at rest with the segment S4 in the pore obstructing sodium entry. (b) The nerve during firing when the segments S4 slide into the body of the channel allowing entry of sodium. (c) The con- figuration during the refractory period when the nerve does not fire and a protein loop between domains III and IV acts as the obstruc- tion to sodium entry. (d) The binding of the local anaesthetic (la) maintaining the channel in the refractory position.
led to the development of different techniques of intra-oral anaesthesia.
Local anaesthetic drugs
Developments in relation to local anaesthetic drugs will be discussed in relation to three areas: first, the intro- duction of articaine to a larger market; second, the development of new longer-acting agents; and finally the development of drugs to reverse the effects of local anaesthesia.
Articaine
Articaine is not a new drug. It has been used exten- sively in Europe and Canada for over 20 years;
however, it has only been available in the UK and the USA for a few years. Articaine has been shown to be a safe and effective local anaesthetic in clinical trials in both adults and children11–15.
Articaine contains a sulphur molecule and this must be remembered in patients allergic to sulphur- containing drugs. It is unique among the amide group of local anaesthetics in that it is initially metabolised in the plasma16. The other amides are metabolised in the liver although prilocaine does undergo some degrada- tion in the lungs. This means that articaine has a much shorter plasma half-life (around 20 min) compared with lidocaine (about 90 min). Therefore, articaine is systemically less toxic than lidocaine16 and is safer should ‘top-up’ anaesthesia be required during longer procedures. It is important to point out that it is the plasma half-life that is reduced, which does not affect the duration of activity of articaine.
There are a number of issues relating to articaine that merit discussion. There is a feeling among general practitioners that articaine with adrenaline is an extremely effective solution and appears better than lidocaine with adrenaline. It has been suggested that it is able to diffuse more widely than other local anaes- thetics16although this has not been supported in some clinical trials17. One study has suggested that palatal injections are not required after buccal anaesthesia with 4% articaine for maxillary dental extractions18. Most studies that have compared articaine with adrenaline to lidocaine with adrenaline have shown the drugs to have comparable efficacy11,19,20. There are data suggesting that articaine has a shorter onset time and longer duration of action compared with lidocaine after infiltration anaesthesia in the maxilla21. One study22 showed that mandibular buccal infiltration with 4% articaine with 1:100 000 adrenaline was more effective in obtaining molar pulpal anaesthesia than a
similar injection of 2% lidocaine with 1:100 000 adrenaline. This may be the result of the increased concentration of local anaesthetic drug as an earlier investigation showed no difference in efficacy follow- ing mandibular buccal infiltration between 4% artic- aine and 4% prilocaine23. A point of interest is that, as far as anaesthesia of the lower first molar is concerned, the infiltration of 4% articaine produced equivalent success to inferior alveolar nerve block with 2%
lidocaine in a similar study population24. This is an interesting finding that merits further investigation as the avoidance of regional block anaesthesia could be an advantage, for example, the reduction of traumatic and chemical injuries to nerve trunks.
An area of controversy concerning the use of 4%
articaine is the suggestion that the production of long- lasting paraesthesia is more likely, compared with other local anaesthetic solutions, when this drug is adminis- tered as a regional block. A greater prevalence of long- lasting paraesthesia, especially of the lingual nerve, has been reported in North America and Europe after the use of 4% articaine compared with lower concentra- tions of mepivacaine and lidocaine25,26. These findings have been questioned by some workers27as large-scale studies have shown no difference in the production of paraesthesias following the intra-oral injection of lidocaine and articaine11. Those who argue that artic- aine does not produce a greater incidence of paraes- thesia claim that, as it is chiefly the lingual nerve that suffers27, this might be due to direct trauma from the needle and that over-reporting of problems is natural when a new drug is introduced to practice. Neverthe- less, nerve damage increases with increasing local anaesthetic concentration28and both 4% articaine and 4% prilocaine have been implicated in a greater inci- dence of paraesthesias than 2% lidocaine25.
Long-acting local anaesthetics
Long-acting local anaesthetics have been used in oral surgery for a number of years. They are not available in dental cartridges in all countries, including the UK.
Drugs such as bupivacaine have been shown to be useful in reducing postoperative discomfort29 and decreasing the need for postoperative analgesia. The most recently developed drugs are ropivacaine and levobupivacaine. Ropivacaine has a shorter elimina- tion half-life compared with bupivacaine30. One useful property attributed to ropivacaine is an inherent vasoconstrictive property31. There is evidence that ropivacaine is as effective with and without additional vasoconstrictor32. This is potentially useful in oral surgery as it might reduce the unwanted effects of local
anaesthesia. Ropivacaine has been shown to be effec- tive in obtaining dental anaesthesia after intra-oral injection33,34; however, when tested during intraliga- mentary anaesthesia, a technique that requires good vasoconstriction for acceptable efficacy, ropivacaine was not as effective as lidocaine with adrenaline in obtaining pulpal anaesthesia35.
Levobupivacaine is a single isomer of bupivacaine. A number of studies have demonstrated similar efficacies of levobupivacaine and bupivacaine36,37. The advantage of the former drug is that it is less toxic compared with the latter38,39. They appear equally effective in obtaining pulpal anaesthesia after inferior alveolar nerve blocks40 and levobupivacaine has been shown to reduce anal- gesic consumption and decrease postoperative pain compared with placebo and injection of lidocaine with adrenaline following oral surgery41.
Reversal of local anaesthesia
Recently there has been a renewed interest in reversal of local anaesthesia.
This is achieved by injecting the alpha-adrenergic antagonist phentolamine mesylate at the end of treat- ment to oppose the effects of the vasoconstrictor (adrenaline) in the original local anaesthetic. The local injection of phentolamine has been shown to signifi- cantly shorten the time taken for return to normal sensation of the lip and tongue after dental anaesthesia.
In one double-blind, placebo-controlled trial phento- lamine reduced return to normal sensation in the upper lip by 78 min and by 56 min in the lower lip42. In another report the duration of soft tissue anaesthesia in the lower lip was reduced by 55% and in the upper lip by 62% when phentolamine was injected compared with a sham-injection control group43. It is anticipated that a suitable formulation for clinical use will be introduced into the USA in 2008. Although reversal of local anaesthesia may be welcomed in some of the dental specialties there will be few indications in oral surgery where postoperative pain control relies to a degree on local anaesthetic action; thus the value of the long-acting agents mentioned earlier.
Delivery systems
The changes in delivery systems relate to the types of syringes used. Modifications have been made to increase safety and comfort. Two will be discussed here, namely safety syringes and electronic (or computer- controlled) delivery systems.
Safety syringes have been developed to decrease the incidence of accidental needle-stick injury. This can be
reduced if needle resheathing is avoided. The impor- tance of the avoidance of accidental needle-stick injury has been recognised in the USA. President Clinton signed the Needle-Stick Safety and Prevention Act in November 200044. Prior to this federal act some 17 states in the USA had passed state legislation in this regard. The Federal act states that ‘the use of safer medical devices, such as needleless systems and sharps with engineered sharps injury protections, when they are used as part of an overall blood-borne pathogens risk-reduction program, can be extremely effective in reducing accidental sharps’ injuries’44. The act does not ban the use of traditional needles, but requires that new systems must be considered for implementation on an annual basis. Thus, advances that reduce the risk of needle stick are to be welcomed. In safety syringe systems the needle and its protective sheath are sup- plied and disposed of as part of the syringe (Fig. 2). The entire assembly is disposed of as a unit, thus needle removal is not required. The introduction of such syringes has been shown to reduce the incidence of
(a)
(b)
Figure 2 A safety syringe showing the protective sheath that guards the needle: (a) sheath partly covering needle; (b) sheath protecting needle.
needle-stick injury45and the system has been shown to aspirate effectively with standard dental cartridges46,47.
The most radical change in the way that local anaes- thetics are delivered has been the introduction of electronic delivery systems. Many different types are available such as the Compudent (previously known as
‘The Wand’), the comfort control syringe, Anaeject and Ora star. A brief description of an electronic system (Fig. 3) illustrates the differences between electronic and conventional cartridge syringes48. The Compudent consists of a free-standing control unit that contains a microprocessor, which controls the flow rate during injection. By dictating the flow rate the pressure created during anaesthetic delivery is controlled. This, in theory, should aid patient comfort. The control unit contains a holder for a standard dental local anaesthetic cartridge46, which is connected via a cannula to the handpiece that holds the needle. This system uses standard medical needles rather than those designed to fit dental cartridge syringes. The latest version includes safe needle guards as described earlier in relation to safety syringes. The signal to inject and aspirate is gov- erned by a foot control. In addition to a controlled injection pressure, another revolutionary aspect of this design is the method of holding the working end. The handpiece is held like a pen, which makes it comfort- able to use. In addition, the ability to rotate the hand- piece between the fingers during injection may overcome needle deflection produced by the bevel of the needle, which is apparent during deep penetration when using a conventional syringe.
The electronic systems deliver local anaesthetic slowly. Speed of injection is related to injection dis- comfort; the faster the injection the greater the dis- comfort. This is apparent in both children and adults24,49. As computerised systems deliver the solu- tion slowly, it would be anticipated that they provide comfortable injections. When the Compudent system is compared at different rates of injection into palatal mucosa, it is apparent that the slower rate produces less discomfort50. Other studies have shown no statistical difference in injection discomfort between computer- ised and traditional syringes in adults51,52; however, in children the computerised system does seem to produce less disruptive behaviour than the traditional system53,54.
There is another potential advantage of the slower delivery that is afforded by electronic syringes. There is evidence that, as well as being safer and more com- fortable, some techniques of intra-oral local anaesthe- sia are more successful when the solution is deposited slowly. This has been shown to be the case after inferior alveolar nerve blocks24and maxillary infiltration55. The incisive/mental block injection does not seem to be influenced by the rate of injection, although as with other methods it is more comfortable when adminis- tered slowly56.
One consequence of the development of computer- ised systems is a renewed interest in different methods of intra-oral anaesthesia. Two block techniques for use in the maxilla have been investigated. These are the anterior middle superior alveolar nerve block dental cartridge
computerised delivery control unit
connecting tubing needle on holder
Figure 3 An example of an electronic local anaesthetic delivery device showing the console, connecting tubing and needle holder.
The unit is activated by a foot control.
(AMSA)57 and the palatal anterior superior alveolar nerve block (PASA)58.
These techniques are novel in that they are advo- cated as means of obtaining pulpal anaesthesia via a palatal approach.
The AMSA technique relies on the presence of multiple small foramina in the palatal surface of the maxilla. Solution deposited slowly in the palatal mucosa midway between the midline and mid- premolar gingival margin (Fig. 4) diffuses through these foramina to enter the cancellous space and then the pulpal supply. It has been proposed that this tech- nique can anaesthetise the pulps of the premolar and anterior maxillary teeth. Although this has been shown to occur, the success reported for the technique is limited and varies between the teeth59(Table 1).
The PASA achieves its effect by injecting solution into the nasopalatine duct (Fig. 5). This has been claimed to produce anaesthesia of the maxillary incisor and canine teeth bilaterally from one injection. The tech- nique has been shown to provide pulpal anaesthesia.
One study in children claimed that clinical effectiveness did not differ between PASA injections and buccal infiltrations60; however, the success is limited in adults61(Table 1).
Overall, these techniques show some promise and might be useful as supplementary techniques in oral surgery; however, at present they are not preferable to standard primary methods of local anaesthesia.
Conclusions
Local anaesthesia has been used intra-orally for over 100 years and continues to develop. New drugs, deliv- ery methods and techniques have increased the pain control armamentarium. Developments continue to improve the comfort and safety of local anaesthetics in dentistry.
References
1. McAuley JE. Carl Koller: the man and the drug. Br Dent J 1985;158:339–42.
2. Hille B. Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 1977;69:497–515.
3. Ulbricht W. Sodium channel inactivation: molecular determinants and modulation. Physiol Rev 2005;85:
1271–301.
4. Catterall WA. From ionic currents to molecular mechanisms: the structure and function of voltage- gated sodium channels. Neuron 2000;26:13–25.
5. Catterall WA. Molecular mechanisms of gating and drug block of sodium channels. Novartis Found Symp 2002;
241:206–18.
6. Caterall WA, Goldin AL, Waxman SG. International Union of Pharmacology. XLVII. Nomenclature and structure–function relationships of voltage-gated sodium channels. Pharmacol Rev 2005;57:397–409.
Figure 4 The position of the needle during the anterior middle superior alveolar nerve block.
Table 1 Reported success rates of the AMSA and PASA injections in adults using a computerised delivery system59,61
Maxillary tooth Success (%) with AMSA Success (%) with PASA
Central incisor 35 55–58
Lateral incisor 58 48–58
Canine 52 32–55
First premolar 42 Second premolar 55
AMSA, anterior middle superior alveolar nerve block; PASA, palatal ante- rior superior alveolar nerve block.
Figure 5 The position of the needle during the palatal anterior superior alveolar nerve block.
7. Hargreaves KM, Keiser K. Local anesthetic failure in endodontics: mechanisms and management. Endod Top 2002;1:26–39.
8. Fozzard HA, Lee PJ, Lipkind GM. Mechanism of local anesthetic drug action on voltage-gated sodium channels. Curr Pharm Des 2005;11:2671–86.
9. Chalothorn D, McCune D, Edelmann SE, Garcia-Cazarin ML, Tsujimoto G, Piascik MT.
Differences in the cellular localization and agonist- mediated internalization properties of the
a1-adrenoreceptor subtypes. Mol Pharmacol 2002;61:
1008–16.
10. Piascik MT, Perez DM. Alpha1-adrenergic receptors:
new insights and directions. J Pharm Exp Ther 2001;
298:403–10.
11. Malamed SF, Gagnon S, Leblanc D. Efficacy of articaine:
a new amide local anesthetic. J Am Dent Assoc 2000;
131:635–42.
12. Malamed SF, Gagnon S, Leblanc D. Articaine hydrochloride: a study of the safety of a new amide local anesthetic. J Am Dent Assoc 2001;132:
177–85.
13. Hersh EV, Giannakopoulos H, Levin LM, Secreto S, Moore PA, Peterson C et al. The pharmacokinetics and cardiovascular effects of high-dose articaine with 1:100 000 and 1:200 000 epinephrine. J Am Dent Assoc 2006;137:1562–71.
14. Moore PA, Boynes SG, Hersh EV, DeRossi SS, Sollecito TP, Goodson JM et al. The anesthetic efficacy of 4 percent articaine 1:200 000 epinephrine: two controlled clinical trials. J Am Dent Assoc 2006;137:
1572–81.
15. Ram D, Amir E. Comparison of articaine 4% and lidocaine 2% in paediatric dental patients. Int J Paediatr Dent 2006;16:252–6.
16. Oertel R, Rahn R, Kirch W. Clinical pharmacokinetics of articaine. Clin Pharmacokinet 1997;33:417–45.
17. Haas DA, Harper DG, Saso MA, Young ER. Comparison of articaine and prilocaine anesthesia by infiltration in maxillary and mandibular arches. Anesth Prog 1990;
37:230–7.
18. Uckan S, Dayangac E, Araz K. Is permanent maxillary tooth removal without palatal injection possible? Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;
102:733–5.
19. Mikesell P, Nusstein J, Reader A, Beck M, Weaver J.
A comparison of articaine and lidocaine for inferior alveolar nerve blocks. J Endod 2005;31:265–70.
20. Vahatalo K, Antila H, Lehtinen R. Articaine and lidocaine for maxillary infiltration anesthesia. Anesth Prog 1993;40:114–16.
21. Costa CG, Tortamano IP, Rocha RG, Francischone CE, Tortamano N. Onset and duration periods of articaine and lidocaine on maxillary infiltration. Quintessence Int 2005;36:197–201.
22. Kanaa MD, Whitworth JM, Corbett IP, Meechan JG.
Articaine and lidocaine mandibular buccal infiltration anesthesia: a prospective randomized double-blind cross-over study. J Endodont 2006;32:296–8.
23. Haas DA, Harper DG, Saso MA, Young ER. Lack of differential effect by Ultracaine (articaine) and Citanest (prilocaine) in infiltration anaesthesia. J Can Dent Assoc 1991;57:217–23.
24. Kanaa MD, Meechan JG, Corbett IP, Whitworth JM.
Efficacy and discomfort associated with slow and rapid inferior alveolar nerve block injection. J Endodont 2006;32:919–23.
25. Haas DA, Lennon D. A 21 year retrospective study of reports of paresthesia following local anesthetic administration. J Can Dent Assoc 1995;61:319–20, 323–6, 329–30.
26. Hillerup S, Jensen R. Nerve injury caused by
mandibular block analgesia. Int J Oral Maxillofac Surg 2006;35:437–43.
27. Malamed SF. Nerve injury caused by mandibular block analgesia. Int J Oral Maxillofac Surg 2006;35:
876–7.
28. Johnson ME, Saenz JA, DaSilva AD, Uhl CB, Gores GJ.
Effect of local anesthetic on neuronal cytoplasmic calcium and plasma membrane lysis (necrosis) in a cell culture model. Anesthesiology 2002;97:1466–76.
29. Moore PA, Dunsky JL. Bupivacaine anesthesia – a clinical trial for endodontic therapy. Oral Surg Oral Med Oral Pathol 1983;55:176–9.
30. Wang RD, Dangler LA, Greengrass RA. Update on ropivacaine. Expert Opin Pharmacother 2001;2:
2051–63.
31. Akerman B, Hellberg AB, Trossvik C. Primary evaluation of the local anesthetic properties of the amino amide agent ropivacaine (LEA 103). Acta Anaethesiol Scand 1988;32:571–8.
32. Hickey R, Candido KD, Ramamurthy S, Winnie AP, Blanchard J, Raza SM et al. Brachial plexus block with a new local anaesthetic: 0.5 per cent ropivacaine. Can J Anaesth 1990;37:732–8.
33. Ernberg M, Kopp S. Ropivacaine for dental anesthesia:
a dose-finding study. Oral Maxillofac Surg 2002;60:1004–10.
34. Kennedy M, Reader A, Beck M, Weaver J. Anesthetic efficacy of ropivacaine in maxillary anterior infiltration.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:406–12.
35. Meechan JG. A comparison of ropivacaine and lidocaine with epinephrine for intraligamentary anesthesia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;93:469–73.
36. Aberg G. Toxicological and local anesthetic effects of optically active isomers of two local anesthetics compounds. Acta Pharmacol Toxicol 1972;31:
273–86.
37. Aps C, Reynolds F. An intradermal study of the local anesthetic and vascular effects of the isomers of bupivacaine. Br J Clin Pharmacol 1978;6:80–3.
38. Bardsley H, Gristwood R, Baker H, Watson N, Nimmo WA. A comparison of the cardiovascular effects of levobupivacaine and rac-bupivacaine following intravenous administration to healthy. Br J Clin Pharmacol 1998;46:245–9.
39. Gristwood RW. Cardiac and CNS toxicity of
levobupivacaine: strengths of evidence for advantage over bupivacaine. Drug Saf 2002;25:153–63.
40. Branco FP, Ranali J, Ambrosano GM, Volpato MC.
A double-blind comparison of 0.5% bupivacaine with 1:200 000 epinephrine and 0.5% levobupivacaine with 1:200 000 epinephrine for the inferior alveolar nerve block. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:442–7.
41. Rood JP, Coulthard P, Snowdon AT, Gennery BA.
Safety and efficacy of levobupivacaine for
postoperative pain relief after the surgical removal of impacted third molars: a comparison with lignocaine and adrenaline. Br J Oral Maxillofac Surg
2002;40:491–6.
42. Laviola M, McGavin SK, Freer GA, Plancich G, Woodbury SC, Marinkovich S et al. Phentolamine mesylate reverses soft-tissue anesthesia. J Dent Res 2006;85(Special Issue A): Abstract No. 560.
43. Yagiela J, Goodson JM, Hersh EV, Moore PA, Papas AS, Rutherford RB. Reversal of soft-tissue anesthesia by an a-adrenergic blocker. J Dent Res 2007;86(Special Issue A): Abstract No. 32.
44. Library of Congress. 106th Congress, 2000. Needlestick Safety and Prevention Act HR 5178. 2000. Available at http://history.n.h.gov/01docs/historical/documents/
PL106-430.pdf.
45. Zakrzewska JM, Greenwood I, Jackson J. Introducing safety syringes into a UK dental school – a controlled study. Br Dent J 2001;190:88–92.
46. International Standards Organisation. Dental cartridges for local anaesthetics. ISO 11499: 1999.
47. Meechan JG, Ramacciato JC, McCabe JF. A comparison of the aspirating abilities of re-usable and partly disposable dental cartridge syringe systems in vitro.
J Dent 2006;34:41–7.
48. International Standards Organisation. Dental cartridge syringes. ISO 9997: 2000.
49. Jones CM, Heidmann J, Gerrish AC. Children’s ratings of dental injection and treatment pain, and the
influence of the time taken to administer the injection.
Int J Paediatr Dent 1995;5:81–5.
50. Primosch RE, Brooks R. Influence of anesthetic flow rate delivered by the Wand Local Anesthetic System on pain response to palatal injections. Am J Dent
2002;15:15–20.
51. Asarch T, Allen K, Petersen B, Beiraghi S. Efficacy of a computerized local anesthesia device in pediatric dentistry. Pediatr Dent 1999;21:421–4.
52. Nicholson JW, Berry TG, Summitt JB, Yuan CH, Witten TM. Pain perception and utility: a comparison of the syringe and computerized local injection techniques.
Gen Dent 2001;49:167–73.
53. Allen KD, Kotil D, Larzelere RE, Hutfless S, Beiraghi S.
Comparison of a computerized anesthesia device with a traditional syringe in preschool children. Pediatr Dent 2002;24:315–20.
54. Gibson RS, Allen K, Hutfless S, Beiraghi S. The Wand vs.
traditional injection: a comparison of pain related behaviors. Pediatr Dent 2000;22:458–62.
55. Babikiov AS, Moskovets ON, Rabinovich SA. Effect of mepivacaine injection speed on the anesthetic effectiveness and localization. Proceedings of the 11th International Congress on Modern Pain Control, International Federation of Anesthesiology Societies, 2006; Abstract No. 1051.
56. Whitworth JM, Kanaa MD, Corbett IP, Meechan JG.
Influence of injection speed on the effectiveness of incisive/mental nerve block: a randomised controlled double blind study in adult volunteers. J Endod 2007;33:1149–54.
57. Friedman MJ, Hochman MN. The AMSA injection: a new concept for local anesthesia of maxillary teeth using a computer-controlled injection system.
Quintessence Int 1998;29:297–303.
58. Friedman MJ, Hochman MN. P-ASA block injection: a new palatal technique to anesthetize maxillary anterior teeth. J Esthet Dent 1999;11:63–71.
59. Lee S, Reader A, Nusstein J, Beck M, Weaver J.
Anesthetic efficacy of the anterior middle superior alveolar (AMSA) injection. Anesth Prog 2004;51:80–9.
60. Ram D, Kassirer J. Assessment of a palatal
approach-anteriorsuperioralveolar (P-ASA) nerve block with the Wand® in paediatric dental patients. Int J Oral Maxillofac Surg 2006;16:348–51.
61. Burns Y, Reader A, Nusstein J, Beck M, Weaver J.
Anesthetic efficacy of the palatal-anterior superior alveolar injection. J Am Dent Assoc 2004;135:1269–76.
