The Journal of the American Dental Association
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J Am Dent Assoc, Vol 132, No 10, 1396-1401.
© 2001 American Dental Association
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RESEARCH

JADA Continuing Education

Pain on injection of prilocaine plain vs. lidocaine with epinephrine

A prospective double-blind study



MICHAEL J. WAHL, D.D.S., DON OVERTON, Ph.D., JON HOWELL, Ph.D., ELI SIEGEL, Ph.D., MARGARET M. SCHMITT, D.M.D. and MICHELE MULDOON, B.A.


   ABSTRACT
TOP
 ABSTRACT
MATERIAL AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Background. Prilocaine has been described as causing less pain on injection than lidocaine with epinephrine, possibly because of the higher pH of the prilocaine anesthetic solution.

Methods. Three hundred ten consecutively seen patients in a general practice received a total of 334 maxillary buccal infiltration or inferior alveolar block injections, administered under clinical conditions by one of two dentists. Immediately afterward, patients rated the pain from each injection on a six-point scale. Twenty of these patients (in 21 separate appointments) received, and were asked to rate the pain associated with, a second injection of a contralateral tooth. The authors analyzed the pain response by operator, location of injection, patient’s age, patient’s sex and anesthetic.

Results. The difference in perceived pain between lidocaine and prilocaine was not statistically significant. Regardless of the anesthetic used, the perceived pain was usually no more than mild. Of 334 injections, 292 (87 percent) were rated as causing either no pain or mild pain.

Conclusions. Under clinical conditions, there is no statistically significant difference between injection pain associated with prilocaine plain vs. that associated with lidocaine with 1:100,000 epinephrine.

Clinical Implications. Since there is no significant difference in associated pain on injection between prilocaine plain and lidocaine with 1:100,000 epinephrine, dentists may prefer lidocaine with epinephrine. Since there is less anesthetic in each cartridge of lidocaine, it may require the use of less anesthetic per patient, and the vasoconstrictor can prolong its duration.

No drugs are more frequently used or more important in most dental practices than local anesthetics. Although the anesthetic effect can lead to a relatively painless dental procedure, the local anesthetic injection itself sometimes can be painful to patients. Ever since the first injectable local anesthetic, cocaine, was discovered in the 19th century, dentists have searched for less painful local anesthetics. Malamed1 wrote, "The primary cause of a mild burning sensation is the [low] pH of the solution being deposited" (emphasis original). As a result, some assert that prilocaine plain (pH 6.0–7.02) elicits less pain on injection than do other anesthetics with lower pH.3,4 In what we will call the "two-anesthetic technique" for painless anesthesia, many dentists inject prilocaine plain first, which, they assert, painlessly numbs the tissue before the subsequent injection of lidocaine with epinephrine.

There is no statistically significant difference between injection pain associated with prilocaine plain vs. that associated with lidocaine with 1:100,000 epinephrine.

A literature search revealed only one study comparing pain on injection of prilocaine plain with that on injection of lidocaine with epinephrine. In a 1999 double-blind study of 150 consecutively seen adult patients, 100 of whom were administered prilocaine plain or lidocaine with 1:100,000 epinephrine, Kramp and colleagues5 reported that the lidocaine with epinephrine was perceived as more painful than prilocaine plain. There have been several studies comparing the pain on injection of buffered lidocaine to that of standard lidocaine. In 1939, Tainter and colleagues6 reported that the intraoral injection of buffered anesthetic solutions (which had a higher pH than standard solutions) actually caused, on average, slightly more pain on injection than did the injection of unbuffered solutions. However, this difference was not enough to be significant. In independent prospective double-blind randomized crossover studies of patients undergoing medical (but not dental) procedures, pH-buffered lidocaine with epinephrine produced less pain than standard lidocaine.7,8 But in a similar study on intraoral injections, there was no significant difference in pain on injection between buffered and standard lidocaine with epinephrine.9 Although a study of pediatric patients showed buffered lidocaine with epinephrine to be less painful than standard lidocaine with epinephrine, the author was not blinded during the injections, and the study relied on children’s memory (at the end of the second appointment) of two injections in two appointments, possibly biasing the results.10 We decided to examine the pain on injection experienced with prilocaine plain vs. that experienced with lidocaine with 1:100,000 epinephrine, which has a significantly lower pH (approximately 4.511) than prilocaine plain (pH 6.0–7.0).

To minimize possible bias from the anticipation of pain, patients were not asked to participate in the study until just after receiving the injection of anesthetic.


   MATERIAL AND METHODS
TOP
 ABSTRACT
 MATERIAL AND METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Our subjects were 310 consecutively seen adult patients older than 18 years of age who had no medical contraindications for undergoing local anesthesia and were scheduled for routine dental procedures with one of two dentists (M.J.W. or M.M.S.) in a general practice between June 1, 1999, and Sept. 24, 1999. We asked these subjects to rate the pain of the injection they had just received. To minimize possible bias from the anticipation of pain, the patients were not asked to participate in the study until just after the injection was given. In each case, patients participating in the study rated only the first injection of the appointment, except for the crossover group, in which patients rated a second injection of the contralateral tooth immediately after rating the first injection.

We purchased from a commercial dental supply company the following items: topical 20 percent benzocaine anesthetic (Benzo-Jel, Henry Schein, Melville, N.Y.); cartridges of prilocaine 4 percent plain (Citanest Plain, AstraZeneca Pharmaceuticals LP, Wilmington, Del.) and lidocaine 2 percent with 1:100,000 epinephrine (Xylocaine with epinephrine, AstraZeneca); and 25-gauge needles (Monoject, Kendall, Mansfield, Mass.), both short (for maxillary injections) and long (for inferior alveolar block injections). A research assistant (M.M.) removed the manufacturer’s sticker from each otherwise identical anesthetic cartridge and replaced each with a coded sticker so as to blind both the dentists and the patients to the identity of the anesthetic used.

We used buccal infiltration injections for maxillary teeth and inferior alveolar block injections for mandibular teeth. For reasons of simplicity, we did not include palatal or other types of injections in the study. Before injecting, the administering dentist first applied topical anesthetic with a cotton applicator. After aspirating, the dentist then deposited the anesthetic solution slowly to minimize discomfort (as recommended by Scarfone and colleagues12). For maxillary injections, the dentist used a short (3/4-inch) 25-gauge needle (Monoject) and deposited approximately one-half cartridge (0.9 milliliter, or mL) of anesthetic solution; for mandibular injections, the dentist used a long (1 1/4-inch) 25-gauge needle (Monoject) and deposited one cartridge (1.8 mL) of anesthetic solution.

Immediately after the injection, we asked patients to rate the pain on a six-point scale: 0 (no pain), 1 (mild pain), 2 (moderate pain), 3 (distressing pain), 4 (horrible pain) or 5 (unbearable pain).13 Some patients were scheduled several times during the study and were asked to rate injection pain at subsequent appointments, as well as at the initial appointment.

The crossover study consisted of 20 patients from the primary study who received a second contralateral injection of the alternate anesthetic immediately after receiving the first injection. These patients were given a total of 21 pairs of injections in 21 separate appointments. For example, a patient receiving infiltration injections on teeth nos. 3 and 14 would receive these injections at the beginning of the appointment, each injection with a new needle and one with each anesthetic. We asked these patients to rate injection pain immediately after each injection. For these patients, only the first injection was included in the primary study, but both injections were included in the crossover design, which was expected to minimize the effect of differences in sensitivity between subjects. We did not include maxillary anterior injections so as to eliminate the possibility of crossover innervation that could affect the result.

We entered the pain scores in a five-factor analysis of variance, or ANOVA (age, three levels; sex, two levels; dentist, two levels; tooth, three levels; drug, two levels). We included age in the analysis because the results showed that scores assigned by elderly patients were lower than those assigned by younger patients; the age categories were 18 to 39 years, 40 to 59 years and 60 to 85 years. The dentist was included as a factor because the two dentists who administered the injections used different sensory masking procedures. Site of injection was categorized as maxillary anterior (teeth nos. 6–11), maxillary posterior (teeth nos. 1–5 and 12–16) or mandibular (teeth nos. 17–32) and was included in the analysis because of the expectation that maxillary anterior injections would be more painful than those at other locations.


   RESULTS
TOP
 ABSTRACT
 MATERIAL AND METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
The dentists administered a total of 334 first injections to 310 patients. Dentist 1 (M.J.W.) administered 204 first injections to 193 patients; Dentist 2 (M.M.S.) administered 130 first injections to 121 patients. (Some patients were in both groups.) The age of the study participants ranged from 18 to 85 years. The great majority (292 of 334; 87 percent) of first injections were rated as either 0 (no pain) or 1 (mild pain). More exactly, the number of injection ratings of 0, 1, 2, 3, 4 and 5 were, respectively, 160, 132, 35, 6, 1 and 0.

None of the main effects of the ANOVA reached statistical significance, but three approached significance. They were patient’s age (P = .09), patient’s sex (P = .08), and drug (P = .053). Table 1Go provides comparisons between subgroups of interest. The overall mean scores with prilocaine and lidocaine were 0.63 and 0.71. The scores for subgroups of different ages showed nonsignificantly lower pain scores with prilocaine in only two of the three subgroups. The 60- to 85-year-old patients had lower scores than either the 18- to 39- or the 40- to 59-year-old patients. Subgroup scores for male and female patients revealed lower pain scores for prilocaine than for lidocaine in both sexes; female patients rated pain slightly higher than did male patients. The subgroup scores for the three injection locations suggest higher pain ratings for maxillary anterior injections than for maxillary posterior or lower injections. Subgroup scores for the two dentists who administered injections differed nonsignificantly.


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  		TABLE 1 PAIN RESPONSE TO PATIENT VARIABLES.

 
Table 2Go shows the results of the small "crossover" experiment. Analysis of these data employed a four-factor ANOVA, which tested the effects of the sequence of the injection (drug injected first vs. drug injected second), injection location (two levels, maxillary posterior and mandibular), administering dentist (two levels) and injected drug (lidocaine vs. prilocaine). All differences were nonsignificant. As in the primary study, patients in the crossover study reported nonsignificantly less pain to the male dentist than to the female dentist and nonsignificantly less pain with prilocaine than with lidocaine. The results also suggest that the second injection was scored as producing more pain than the first (P = .19).


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  		TABLE 2 RESULTS OF THE CROSSOVER INJECTIONS.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIAL AND METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
This study showed that for maxillary buccal infiltration injections and for inferior alveolar block injections, there was not a statistically significant difference in pain response between patients who received lidocaine with 1:100,000 epinephrine and patients who received prilocaine plain. Some strengths of our study include the fact that it was prospective and double-blind and that the total numbers of patients and injections were larger than in other studies of pain after injections.5,7–10,12–16 Some weaknesses of our study include the fact that rating pain is by its very nature subjective in any patient and that for the primary study, we were comparing pain responses among individual patients. In the crossover study, there were only 20 patients, so the number of patients may be too small to allow for any definitive conclusions. Since we did not include palatal injections in our study, there may be a difference in pain response between anesthetics for these injections.

Our results differed from those of Kramp and colleagues5 in that we found no significant difference in pain perception between the injection of prilocaine plain vs. that of lidocaine with 1:100,000 epinephrine. By contrast, Kramp and colleagues found that the injection of prilocaine plain was perceived as less painful that of lidocaine with 1:100,000 epinephrine. There were two important distinctions in study design that may account for the difference in results. First, our study involved more than three times as many patients; we administered 334 first injections to 310 patients, whereas the Kramp and colleagues study involved only 100 injections given to 100 patients (there also were 50 patients who received injections of mepivacaine with 1:20,000 levonordefrin). Perhaps the differences in perceived pain between these anesthetics lessen as the study size increases. Second, we deliberately conducted our study under clinical conditions, including the administration of topical anesthetic before each injection. In the Kramp and colleagues study, topical anesthetic was not used "to eliminate that potential variable."5 Topical anesthetic may have played a role in reducing perceived pain differences before injections, but since topical anesthetic normally is given before injections in clinical practice, we thought it was important to include it here.

In the first experiment, the difference between pain ratings with prilocaine and lidocaine approached significance, and the size of this difference was indicated by the overall average scores of 0.63 and 0.71, respectively. This is equivalent to the results that would be obtained if, on average, one patient of each 12 scored pain one unit higher with lidocaine than with prilocaine. It seems that this small difference in rated pain should not determine selection between these two drugs if other clinical factors mitigate in favor of one or the other.

The other effects and trends in the primary data are not exceptional. Apparently, older patients are either less sensitive to pain or less prone to report pain, as their pain ratings were lower than those of younger and middle-aged patients. Perhaps female patients experienced more pain or were more willing to report pain as compared with male patients, but this between-sex difference was very small and statistically insignificant. Injections in the maxillary anterior location generally are believed to be more painful than injections in the other locations tested, and they were so according to our data. The two dentists differed in many respects. Dentist 1 was male; Dentist 2 was female. To mask pain during injection, Dentist 1 shook the patient’s lip or cheek, whereas Dentist 2 had patients inspect posters on the ceiling. Considering these differences, it is not surprising that patient pain scores differed to some degree.

We included age in the analysis because the results showed that scores assigned by elderly patients were lower than those assigned by younger patients.

None of the results of the second "crossover" study was statistically significant. The results suggest the same difference between drugs seen in the primary study. Additionally, the results suggest that patients reported more pain after the second injection than after the first, irrespective of which drug was administered first.

A positive feature of this study was that it was conducted under clinical conditions, including the application of topical anesthetic before injections, distraction (in Dentist 1’s groups, shaking of the cheek and/or lips during injection; in Dentist 2’s group, encouraging the patient to focus on posters on the ceiling during the injection) and slow injection. The slow injection of solution can lessen tissue distension and allow time for neutralization by the tissues of the acidity of the anesthetic solutions. The vast majority of responses for either anesthetic was either 0 (no pain) or 1 (mild pain). There may have been more pain elicited and perhaps more of a difference between anesthetics had no topical anesthetic or distraction techniques been used. Perhaps administration of prilocaine plain is less painful under nonclinical conditions, but this difference apparently is clinically insignificant.

A disadvantage of the "two-anesthetic technique" not usually mentioned is the possibility of more postoperative (as opposed to intraoperative) pain in two injection sites instead of one. Since lidocaine with 1:100,000 epinephrine does not cause substantially more injection pain than prilocaine plain, only one anesthetic should be necessary for a relatively painless injection.

Vasoconstrictors are an important addition to local anesthetics, and anesthetics with them should be preferred to plain anesthetics unless specifically contraindicated by the patient’s medical status.1 They generally decrease the amount of anesthetic necessary, decrease the absorption of the anesthetic and prolong the anesthetic effect. The maximum dose of lidocaine 2 percent with 1:100,000 epinephrine is 500 milligrams, or mg, (13.9 cartridges) for 150-pound, or lb., adults. The maximum dose of prilocaine 4 percent plain is 600 mg (only eight cartridges) for 150-lb. adults. Therefore, a greater number of cartridges of lidocaine with 1:100,000 epinephrine than prilocaine plain can be administered safely. Pulpal anesthesia usually will last longer with lidocaine with epinephrine than with prilocaine plain.1 Furthermore, regardless of whether prilocaine or lidocaine is used, there usually is either only mild pain or no pain from the injection. As a result, clinicians may wish to choose lidocaine with epinephrine over prilocaine plain for most patients.


   CONCLUSIONS
TOP
 ABSTRACT
 MATERIAL AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
Our study showed that there was not a statistically significant difference in pain response between injections of prilocaine plain vs. injections of lidocaine with 1:100,000 epinephrine in maxillary buccal infiltration or inferior alveolar block injections. In a comparison of prilocaine plain with lidocaine with 1:100,000 epinephrine, other factors appear to be more important predictors of pain on injection than the anesthetic solution.

In conclusion:

– There was no significant difference in perceived pain on injection of lidocaine with 1:100,000 epinephrine vs. pain on injection of prilocaine plain.
– Under the clinical conditions in this study, regardless of whether lidocaine with 1:100,000 epinephrine or prilocaine plain was administered, subjects usually experienced only mild pain on injection or no pain at all.
– There was a difference in perceived pain on injection of local anesthetics based on the location of the injection. Maxillary anterior injections were perceived to be more painful than maxillary posterior or mandibular inferior alveolar block injections.
– The painfulness of local anesthetic injections of lidocaine with 1:100,000 epinephrine or prilocaine plain may not relate to the pH of the solution. Further study of the role of pH and injection pain is warranted, including the study of other anesthetic solutions.

Our study showed that most local anesthetic injections of either lidocaine with 1:100,000 epinephrine or prilocaine plain can be relatively painless.


   FOOTNOTES
 

Dr. Wahl is in private practice, Wahl Family Dentistry, 1601 Concord Pike, Wilmington, Del. 19803, e-mail "WahlMichaelJ{at}aol.com". Address reprint requests to Dr. Wahl.


Dr. Overton is a professor, Department of Psychology, Temple University, Philadelphia.


Dr. Howell is a senior research associate, DuPont Company, Wilmington, Del.


Dr. Siegel is a metrics specialist, SBC Corporation, Hoffman Estates, Ill.


Dr. Schmitt is in private practice, Wahl Family Dentistry, Wilmington, Del.


At the time this article was submitted to JADA, Ms. Muldoon was a research assistant, Wahl Family Dentistry, Wilmington, Del., and an undergraduate student, University of Delaware, Newark, Del. She now is a student, Villanova University School of Law, Villanova, Pa.


   REFERENCES
TOP
 ABSTRACT
 MATERIAL AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Malamed SF. Handbook of local anesthesia. 4th ed. St. Louis: Mosby; 1997.

  2. Citanest Plain (prilocaine HCl injection, USP). (package insert 021565R14) Wayne, Pa.: Astra; 1997.

  3. Strupp W. A clinical technique for giving painless injections. Dent Today 1998;17(12):34–7.[Medline]

  4. Jones D. Smooth running in a small office. Dent Today 1999;18(4): 8–11.

  5. Kramp LF, Eleazer PD, Scheetz JP. Evaluation of prilocaine for the reduction of pain associated with transmucosal anesthetic administration. Anesth Prog 1999;46:52–5.[Medline]

  6. Tainter ML, Throndson AH, Moose SM. Alleged clinical importance of buffered local anesthetic solutions. JADA 1939;26:920–7.

  7. Masters JE. Randomised control trial of pH buffered lignocaine with adrenaline in outpatient operations. Br J Plast Surg 1998;51:385–7.[Medline]

  8. Fitton AR, Ragbir M, Milling MAP. The use of pH adjusted lignocaine in controlling operative pain in the day surgery unit: a prospective, randomised trial. Br J Plast Surg 1996;49:404–8.[Medline]

  9. Primosch RE, Robinson L. Pain elicited during intraoral infiltration with buffered lidocaine. Am J Dent 1996;9:5–10.[Medline]

  10. Crose VW. Pain reduction in local anesthetic administration through pH buffering. J Indiana Dent Assoc 1991;70(2):24–7.[Medline]

  11. 1995 Physicians’ desk reference. Montvale, N.J.: Medical Economics Press; 1995:580.

  12. Scarfone RJ, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med 1998;31:36–40.[Medline]

  13. Hutchins HS, Young FA, Lackland DT, Fishburne CP. The effectiveness of topical anesthesia and vibration in alleviating the pain of oral injections. Anesth Prog 1997;44:87–9.[Medline]

  14. Meechan JG, Winter RA. A comparison of topical anaesthesia and electronic nerve stimulation for reducing the pain of intra-oral injections. Br Dent J 1996;181:333–5.[Medline]

  15. Colaric KB, Overton DT, Moore K. Pain reduction in lidocaine administration through buffering and warming. Am J Emerg Med 1998;16:353–6.[Medline]

  16. Jones JS, Plzak C, Wynn BN, Martin S. Effect of temperature and pH adjustment of bupivacaine for intradermal anesthesia. Am J Emerg Med 1998;16:117–20.[Medline]





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