Long-acting Local Anesthetic Research Articles

Protein kinases participate in the contraction in response to levobupivacaine in the rat aorta

Levobupivacaine is a long-acting amide local anesthetic that intrinsically produces vasoconstriction both in vivo and in vitro. Levobupivacaine increases intracellular calcium concentrations ([Ca2+]i) in vascular smooth muscle cells. The goals of this in vitro study were to investigate whether levobupivacaine-induced contraction is associated with increased Ca2+ sensitivity and to identify the protein kinases involved in mediating contraction in response to levobupivacaine in isolated rat aortic smooth muscle. The effect of levobupivacaine and potassium chloride (KCl) on the [Ca2+]i and tension was measured simultaneously with acetoxymethyl ester of fura-2-loaded aortic strips. Cumulative levobupivacaine concentration–response curves were generated in the presence or absence of the following antagonists: GF 109203X; Y-27632; genistein; SP600125; PD 98059; and SB 203580. Levobupivacaine-induced protein kinase C (PKC), extracellular signal-regulated kinase (ERK), and c-Jun NH2-terminal kinase (JNK) phosphorylation and Rho-kinase (ROCK-2) membrane translocation were detected in rat aortic vascular smooth muscle cells using Western blotting. The slope of the [Ca2+]i-tension curve for levobupivacaine was higher than that for KCl. Y-27632, GF 109203X, and SP600125 attenuated levobupivacaine-induced contraction in a concentration-dependent manner. Genistein, PD 98059, and SB 203580 attenuated levobupivacaine-induced contraction. Pretreatment with GF 109203X and Y-27632 inhibited levobupivacaine-induced PKC phosphorylation and Rho-kinase (ROCK-2) membrane translocation, respectively. Pretreatment with SP600125 or PD 98059 attenuated the levobupivacaine-induced phosphorylation of JNK and ERK, respectively. These results indicate that levobupivacaine-induced contraction involving an increase in myofilament Ca2+ sensitivity involves the primary activation of Rho-kinase-, PKC-, and JNK-mediated pathways of rat aortic smooth muscle.

Continuous peripheral nerve blocks

A continuous peripheral nerve block—also termed “perineural local anesthetic infusion”—involves the percutaneous insertion of a catheter adjacent to a peripheral nerve, followed by local anesthetic administration via the catheter, providing anesthesia/analgesia for a prolonged period of time. The most-common indication for continuous peripheral nerve blocks is analgesia following painful surgical procedures; but, they are also used for inducing a sympathectomy and vasodilation following digit transfer/replantation, a vascular accident, limb salvage, or peripheral embolism; treating intractable hiccups; alleviating the vasospasm of Raynaud’s disease; and treating chronic pain such as phantom limb pain, cancer-induced pain, complex regional pain syndrome, and trigeminal neuralgia. Continuous peripheral nerve blocks may also provide pain control during medical transport, or awaiting surgical correction. The most common catheter insertion techniques include electrical stimulation and ultrasound-guidance. Long-acting local anesthetic is usually the sole infusate, and is optimally delivered with a continuous basal infusion with available patient-controlled bolus doses. Benefits are dependent upon analgesia improvement, and include decreasing pain, supplemental analgesic consumption, opioid-related side effects, sleep disturbances, patient dissatisfaction, time until discharge readiness, and actual hospitalization duration. Additional possible benefits include improvements in ambulation/functioning and an accelerated resumption of passive joint range-of-motion. Most benefits occur during the infusion itself, but a few studies suggest prolonged benefits following catheter removal in some cases. Minor complications occur at approximately the incidence as for single-injection peripheral nerve blocks; but, major risks including nerve injury are extraordinary uncommon.

Magnesium added to bupivacaine prolongs the duration of analgesia after interscalene nerve block

Local anesthetic adjuvants have been studied previously in an attempt to prolong the duration of analgesia after peripheral nerve blockade. Magnesium has been shown to have an antinociceptive effect in animal and human pain models. We evaluated the effects of adding magnesium sulphate to long-acting local anesthetics for interscalene nerve block to prolong the duration of analgesia and improve the analgesic quality. We enrolled 66 patients undergoing arthroscopic rotator cuff repair. The interscalene nerve block was performed with 0.5% bupivacaine 20mL with epinephrine (1:200,000) plus either 10% magnesium sulphate 2mL (Magnesium Group) or normal saline 2mL (Saline Group). The following data were recorded for 24 hr after surgery: onset times and durations of sensory and motor blocks, analgesic duration, the pain numeric rating scale (NRS), postoperative fentanyl consumption, and complications. The duration of analgesia was longer in the Magnesium Group than in the Saline Group [mean and (standard deviation) 664 (188) min vs 553 (155) min, respectively; P=0.017]. Patients in the Magnesium Group had significantly reduced pain NRS scores at 12 hr (P=0.012), but the cumulative fentanyl consumption was similar in both groups. The onset times and durations of sensory and motor blocks were not significantly different between the two groups. The addition of magnesium sulphate to a bupivacaine-epinephrine mixture for interscalene nerve block prolongs the duration of analgesia and reduces postoperative pain.

Postoperative Wound Management after Cleft Lip Surgery

Our aim was to describe the postoperative management and wound care protocol after primary cleft lip closure, as it has been used in the Bruges Cleft and Craniofacial Center at the supraregional teaching hospital AZ St. Jan, Bruges, between June 1, 1991, and July 1, 2009. The postoperative management and wound care included the use of a Logan bow, long-acting local anesthetic, elbow restraints, antibiotic therapy, crust removal with normal saline solution, and a special local wound ointment that was prepared at our center. During the last 19 years, 199 unilateral and 103 bilateral cleft lip patients have been repaired. 2.6% showed postoperative infection and/or dehiscence. One percent required readmission for reoperation. In 1.6%, inflammatory reaction was treated with oral antibiotics. The specific wound dressing ointment, as it is prepared in our department, could meet the requirements of primary wound management after cleft lip closure.

Levobupivacaine-induced contraction of isolated rat aorta is calcium dependent

Levobupivacaine is a long-acting local anesthetic that intrinsically produces vasoconstriction in isolated vessels. The goals of this study were to investigate the calcium-dependent mechanism underlying levobupivacaine-induced contraction of isolated rat aorta in vitro and to elucidate the pathway responsible for the endothelium-dependent attenuation of levobupivacaine-induced contraction. Isolated rat aortic rings were suspended to record isometric tension. Cumulative levobupivacaine concentration-response curves were generated in either the presence or absence of the antagonists verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, Gd(3+), N(W)-nitro-l-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and methylene blue, either alone or in combination. Verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, low calcium concentrations, and calcium-free Krebs solution attenuated levobupivacaine-induced contraction. Gd(3+) had no effect on levobupivacaine-induced contraction. Levobupivacaine increased intracellular calcium levels in vascular smooth muscle cells. L-NAME, ODQ, and methylene blue increased levobupivacaine-induced contraction in endothelium-intact aorta. SKF-96365 attenuated calcium-induced contraction in a previously calcium-free isotonic depolarizing solution containing 100mmol/L KCl. Levobupivacaine-induced contraction of rat aortic smooth muscle is mediated primarily by calcium influx from the extracellular space mainly via voltage-operated calcium channels and, in part, by inositol 1,4,5-trisphosphate receptor-mediated release of calcium from the sarcoplasmic reticulum. The nitric oxide - cyclic guanosine monophosphate pathway is involved in the endothelium-dependent attenuation of levobupivacaine-induced contraction.

Comparison of Neosaxitoxin Versus Bupivacaine via Port Infiltration for Postoperative Analgesia Following Laparoscopic Cholecystectomy

Wound infiltration with available local anesthetics generally provides analgesia for less than 8 hrs. The site 1 sodium-channel toxin neosaxitoxin (neoSTX) produced analgesia for over 24 hrs in animals and human volunteers. In this randomized, double-blind trial, we examined the postoperative course of patients undergoing laparoscopic cholecystectomy under a standardized general anesthesia with wound infiltration using either neoSTX or bupivacaine. We hypothesized that neoSTX would reduce pain compared with bupivacaine at 12 hrs postoperatively. Patients received preincisional infiltration of laparoscope entry sites with 20 mL containing either neoSTX (total dose, 100 μg) or bupivacaine 0.25% (total dose, 50 mg). The primary outcome measure was the visual analog pain score at 12 hrs postoperatively. Secondary outcomes included repeated pain scores at rest and with movement,analgesic use, functional recovery, and adverse effects. Groups were compared using Mann-Whitney U tests for pain scores, Fisher exact test for proportions of patients with severe pain and complete analgesia, and Kaplan-Meier curves for time to full recovery. Among 137 subjects, 69 were randomized to neoSTX and 68 to bupivacaine. Median pain scores at rest and with movement 12 hrs postoperatively were lower in the neoSTX group compared with the bupivacaine group (P<0.01). Additional pain measures and recovery parameters also favored neoSTX. No serious adverse events occurred,and no adverse events were more frequent in the neoSTX group. NeoSTX shows promise as a long-acting local anesthetic. Future studies will examine dose response, combination formulations, and safety with dose escalation.

LIA–PAI for Arthroplasty Seems Better Than Nothing but Is It Best?

In this issue of Pain Medicine , Wei Liu and XiaoHua Li studied a solution of ropivacaine, morphine, and epinephrine (adrenaline) injected intra-articularly and infiltrated peri-articularly for analgesia after hip arthroplasty [1]. They called this local and intraarticular infiltration analgesia (LIA). Related techniques are periarticular infiltration (PAI), periarticular injection, and periarticular analgesia [2–4]. The term LIA–PAI will be used here. LIA–PAI infiltration solutions contain long-acting local anesthetics commonly with additives like morphine, epinephrine (adrenaline), nonsteroidal anti-inflammatory drugs, corticosteroids, and antibiotics. Major arthroplasty is painful and causes the patient suffering [5]. Poorly treated pain contributes to impaired physical rehabilitation, immobility-associated complications such as pneumonia and deep venous thrombosis, stress-precipitated cardio- and cerebro-vascular …

Comparison of Preincisional Infiltrated Levobupivacaine and Ropivacaine for Acute Postoperative Pain Relief After Septorhinoplasty

Background To maintain a high standard of patient care, it is essential to provide adequate pain management in patients who undergo nasal surgery. Levobupivacaine and ropivacaine are relatively new long-acting local anesthetics. Objective The aim of this study was to compare the analgesic effect and blood loss of preincisional levobupivacaine HCl 0.25% and ropivacaine HCl 0.375% in patients undergoing septorhinoplasty. Methods Sixty American Society of Anesthesiologists (ASA) I and II patients (18–55 years old) who were scheduled for elective open technique septorhinoplasty under general anesthesia were recruited for this study. The anesthetic technique was standardized for both groups. Preoperative and postoperative hemoglobin levels were recorded for all patients. Patients were assigned randomly to 1 of 2 study groups, and preincisional surgical field infiltration with 5 mL of 0.5% levobupivacaine plus 5 mL of 0.9% saline (group L; n = 30) or 5 mL of 0.75% ropivacaine plus 5 mL of 0.9% saline (group R; n = 30) was performed by the same surgeon. The degree of pain was measured by visual analogue scale (VAS) for pain and recorded at multiple time points in all patients after surgery. Results The analgesic effect at 2 hours in the postanesthesia care unit (PACU) and at 24 hours postoperatively did not differ significantly between the 2 local anesthetics ( P > 0.05). Pain scores of patients decreased after the 24 hours in levobupivacaine group and ropivacaine group when compared with 0-minute VAS values, and this was statistically significant ( P < 0.05). No significant difference was observed between groups with respect to the preoperative and postoperative hemoglobin ( P = 0.767 and 0.824, respectively) values. Conclusions Local tissue infiltration with 0.25% levobupivacaine or 0.375% ropivacaine is similarly effective in reducing the postoperative pain associated with septorhinoplasty.

Epidural anesthesia and post-operative analgesia for bilateral inguinal mesh hernioplasty

Objectives:Ropivacaine is a long-acting amide local anesthetic, which is structurally very similar to bupivacaine but produces less motor block and less cardiac and central nervous system toxicity. It is also about 40% less potent than bupivacaine. Our double blind study was designed to compare the clinical efficacy of the equipotent doses of ropivacaine 0.75% and bupivacaine 0.5% for epidural anesthesia and ropivacaine 0.2% and bupivacaine 0.125% for post-operative analgesia in patients undergoing bilateral mesh hernioplasty.Methods:Sixty-one patients were randomized to receive 15 ml of 0.75% ropivacaine or 0.5% bupivacaine. Sensory and motor block characteristics were compared. Changes in heart rate, mean arterial blood pressure, and adverse effects were noted. For post-operative analgesia, 0.2% ropivacaine and 0.125% bupivacaine were given as continuous epidural infusion. Analgesia using VAS scores, motor block, volume of local anesthetic used and patient satisfaction was assessed.Results:There was no significant variation in the sensory block profile. A greater intensity of motor block was achieved with bupivacaine in the beginning but by 30 minutes the difference was not significant. Duration of motor block was similar in the two groups. Visual analog scale scores were similar in both groups during the post-operative period, with a similar motor block profile. No major side effects were noted in any group.Conclusion:The equipotent doses of ropivacaine and bupivacaine provided good quality epidural anesthesia and post-operative analgesia.

Ropivacaine: A review of its pharmacology and clinical use

Ropivacaine is a long-acting amide local anaesthetic agent and first produced as a pure enantiomer. It produces effects similar to other local anaesthetics via reversible inhibition of sodium ion influx in nerve fibres. Ropivacaine is less lipophilic than bupivacaine and is less likely to penetrate large myelinated motor fibres, resulting in a relatively reduced motor blockade. Thus, ropivacaine has a greater degree of motor sensory differentiation, which could be useful when motor blockade is undesirable. The reduced lipophilicity is also associated with decreased potential for central nervous system toxicity and cardiotoxicity. The drug displays linear and dose proportional pharmacokinetics (up to 80 mg administered intravenously). It is metabolised extensively in the liver and excreted in urine. The present article details the clinical applications of ropivacaine and its current place as a local anaesthetic in the group.

The Effect of Mixing 1.5% Mepivacaine and 0.5% Bupivacaine on Duration of Analgesia and Latency of Block Onset in Ultrasound-Guided Interscalene Block

Short- and long-acting local anesthetics are commonly mixed to achieve nerve blocks with short onset and long duration. However, there is a paucity of data on advantages of such mixtures. We hypothesized that a mixture of mepivacaine and bupivacaine results in a faster onset than does bupivacaine and in a longer duration of blockade than does mepivacaine. Sixty-four patients undergoing arthroscopic shoulder surgery (ages 18 to 65 years; ASA physical status I-II) with ultrasound-guided interscalene brachial plexus block as the sole anesthetic were studied. The subjects were randomized to receive 1 of 3 study solutions: 30 mL of mepivacaine 1.5%, 30 mL of bupivacaine 0.5%, or a mixture of 15 mL each of bupivacaine 0.5% and mepivacaine 1.5%. The block onset time and duration of motor and sensory block were assessed. Onset of sensory block in the axillary nerve distribution (superior trunk) was similar among the 3 groups (8.7 ± 4.3 minutes for mepivacaine, 10.0 ± 5.1 minutes for bupivacaine, and 11.3 ± 5.3 minutes for the combination group; P = 0.21 between all groups). The duration of motor block for the combination group (11.5 ± 4.7 hours) was between that of the bupivacaine (16.4 ± 9.4 hours) and mepivacaine (6.0 ± 4.2 hours) groups (P = 0.03 between bupivacaine and combination groups; P = 0.01 between mepivacaine and combination groups). Duration of analgesia was the shortest with mepivacaine (4.9 ± 2.4 hours), longest with bupivacaine (14.0 ± 6.2 hours), and intermediate with the combination group (10.3 ± 4.9 hours) (P < 0.001 for mepivacaine vs. combination group; P = 0.01 for bupivacaine vs. combination group). For ultrasound-guided interscalene block, a combination of mepivacaine 1.5% and bupivacaine 0.5% results in a block onset similar to either local anesthetic alone. The mean duration of blockade with a mepivacaine-bupivacaine mixture was significantly longer than block with mepivacaine 1.5% alone but significantly shorter than the block with bupivacaine 0.5% alone.

Regional Anesthesia and Eye Surgery

Regional Anesthesia and Eye Surgery

Femoral Nerve Block for Analgesia in Patients Having Knee Arthroplasty

Femoral Nerve Block for Analgesia in Patients Having Knee Arthroplasty

Development and validation of a LC method for the enantiomeric purity determination of S-ropivacaine in a pharmaceutical formulation using a recently commercialized cellulose-based chiral stationary phase and polar non-aqueous mobile phase

Ropivacaine is the first enantiomerically pure long-acting local anaesthetic used for surgical anaesthesia and post-operative pain relief.A liquid chromatographic (LC) method using acetonitrile as the main solvent and cellulose tris(4-chloro-3-methylphenylcarbamate) coated on silica as chiral stationary phase was successfully developed and applied for the enantiomeric purity determination of S-ropivacaine in a pharmaceutical formulation (Naropin®). The key role played by the acidic additive (trifluoroacetic acid or formic acid) in the enantioseparation of basic drugs in these LC systems was demonstrated by the reversal of ropivacaine enantiomers elution order observed when both acids were compared. In order to elute the enantiomeric impurity (R-ropivacaine) before S-ropivacaine, formic acid (FA) was selected. The temperature and the percentages of acidic additive and hexane in the mobile phase were found to significantly influence the retention and resolution of these enantiomers. The optimized mobile phase consisted of ACN/0.1% DEA/0.2% FA/5% hexane (v/v/v/v). The temperature was set at 35°C to avoid the interference from a peak system related to the presence of water in the sample on ropivacaine enantiomers.The LC method was then fully validated applying the strategy based on total measurement error and accuracy profiles. The accuracy profile obtained by linear regression after square root transformation was selected, the acceptance limits being settled at ±10% for the intended use of this analytical method. The relative bias was lower than 1.5%, while the RSD values for repeatability and intermediate precision were both below 1.0%. The limit of detection (LOD) and the limit of quantification (LOQ) were found to be about 0.2 and 1.0μg/mL, respectively, corresponding to 0.02 and 0.1% of the enantiomeric impurity in S-ropivacaine.

Radiotelemetric and Symptomatic Evaluation of Pain in the Rat After Laparotomy: Long-Term Benefits of Perioperative Ropivacaine Care

Effective relief of acute and long-term postoperative pain is of utmost importance to patients undergoing surgery. Here, we worked on a controlled procedure of abdominal surgery in the rat inducing persistent postoperative pain symptoms for up to 10 days and tested the efficacy of perioperative care with the local anesthetic ropivacaine. Laparotomy was likewise used to implant radiotelemetric probes by which electrocardiogram, body temperature, and locomotor activity were recorded in freely moving animals. We showed that postoperative pain symptoms (mechanical allodynia) measured in periphery of the scar were associated over time with persistent tachycardia, elevated heart rate variability, and loss of mobility. Furthermore, a single subcutaneous infiltration of the local anesthetic ropivacaine in the periphery of the abdominal incision was sufficient to prevent the appearance of allodynia and the associated cardiac and motor signs of pain, monitored by radiotelemetry. These beneficial effects were observed when the infiltration was performed in the perioperative period, but not later. This study on freely moving animals exhibiting long-lasting postoperative pain symptoms and altered autonomic/motor function illustrates well the importance of the timing of preemptive analgesia care with long-acting local anesthetics. Moreover, it emphasizes the utility of monitoring heart rate variability to quantify spontaneous expression of long-lasting postoperative pain. Speeding the recovery time after surgery using perioperative ropivacaine care is of significant clinical relevance because it might limit the risk of chronic pain and postoperative complications. In humans, chronobiological analysis of heart rate variability could also help quantify spontaneous pain expression with minimal emotional bias.

Anaesthesia for endoscopic sinus surgery

Endoscopic sinus surgery is commonly performed and has a low risk of major complications. Intraoperative bleeding impairs surgical conditions and increases the risk of complications. Remifentanil appears to produce better surgical conditions than other opioid analgesics, and total intravenous anaesthesia with propofol may provide superior conditions to a volatile-based technique. Moderate hypotension with intraoperative beta blockade is associated with better operating conditions than when vasodilating agents are used. Tight control of CO(2) does not affect the surgical view. The use of a laryngeal mask may be associated with improved surgical conditions and a smoother emergence. It provides airway protection equivalent to that provided by an endotracheal tube in well-selected patients, but offers less protection from gastric regurgitation. Post-operatively, multimodal oral analgesia provides good pain relief, while long-acting local anaesthetics have been shown not to improve analgesia.

AMPK Attenuates Bupivacaine-induced Neurotoxicity

Bupivacaine has been widely used as a long-acting local anesthetic. However, evidence strongly suggests that bupivacaine causes apoptosis. AMP-activated protein kinase (AMPK) regulates metabolic homeostasis and mediates cellular protection from stress. We hypothesized that AMPK may be cytoprotective in bupivacaine-treated Schwann cells. To explore this, we applied bupivacaine to the RT4-D6P2T Schwann cell line. The expression of phosphorylated AMPK was compared after bupivacaine treatment. Bupivacaine induced cell death in a time- and dose- [50% lethal dose (LD50) = 316 µM] dependent manner, and increased expression of phosphorylated AMPK after bupivacaine treatment. Bupivacaine-induced cytotoxicity was attenuated by AICAR (an AMPK activator), whereas compound C (an AMPK inhibitor) enhanced it. The cytoprotective effect of AICAR was reversed in the presence of iodotubercidin, an AICAR inhibitor. Our results suggest that the AMPK pathway may protect Schwann cells from bupivacaine-induced cytotoxicity.

Levobupivacaine

Levobupivacaine (Chirocaine) is a long-acting amide local anaesthetic that is effective when administered as an epidural, spinal, peripheral nerve or ocular block, or by topical application or local infiltration. In comparative trials, its clinical effects were not generally significantly different from those of bupivacaine or ropivacaine, although there was some variability in efficacy findings in different clinical populations. Levobupivacaine was generally well tolerated. Levobupivacaine provides effective anaesthesia and analgesia for a wide range of clinical populations and is a useful alternative to bupivacaine.

Phenothiazine-type Antipsychotics Elicit Cutaneous Analgesia in Rats

Local anesthetics exert their anesthetic and analgesic effects by blocking the sodium channels in the nervous system. Phenothiazine-type antipsychotics also block sodium channels, but the local anesthetic characteristics of these drugs have not been evaluated. The aim of this study was to evaluate the cutaneous analgesic effect of phenothiazine-type antipsychotics. Using a subcutaneous injection model in rats, we tested the cutaneous analgesic effects of six phenothiazine-type antipsychotics (mesoridazine, promazine, chlorpromazine, fluphenazine, perphenazine and triflupromazine) at a dose of 0.6 mumol, and compared them with those of bupivacaine and lidocaine. A saline injection was used as the control. All six phenothiazine-type antipsychotics elicited cutaneous analgesia. At the dose of 0.6 mumol, the potencies of mesoridazine and promazine were similar to that of bupivacaine; the other four drugs were less potent (p<0.001 for each comparison). Mesoridazine had a longer duration of action than bupivacaine (p<0.001). In terms of ED(50) values, mesoridazine was more potent and longer-acting than bupivacaine and lidocaine (p<0.01 for each comparison). Of the antipsychotic drugs tested, mesoridazine is potentially the best candidate for development into a potent, long-acting local anesthetic. However, toxicity studies are needed before these agents can be used clinically as analgesics.

Comparison of bupivacaine and lidocaine use for postoperative pain control in endodontics.

Many patients suffer from mild, moderate or severe pain during or after root canal therapy. Theoretically, post-operative pain control can be achieved by using long-acting local anesthetics. The aim of this study was to evaluate the efficacy of a long acting anesthesia, bupivacaine, on preventing post-operative pain associated with endodontic treatment, and to compare it with lidocaine. This study was a double blind and randomized clinical trial on 30 patients' anterior maxillary teeth. The patients were divided into two groups of fifteen. One group was administered lidocanine (2% with 1:100000 epinephrine) local anesthesia and the other group was given bupivacaine (0.5% without epinephrine). The pain in patients were compared using the visual analogue scale (VAS) at definite times i.e. before treatment, during treatment and 2,4,6,8,10,12,24,36 and 48 hours after operation. Data were analyzed using One-way ANOVA tests. Bupivacaine significantly decreased postoperative pain compared to lidocaine. Postoperative pain was directly related to preoperative pain. Women reported more pain, though significant difference in postoperative pain report was not found between different ages. In conclusion, a single dose of bupivacaine 0.5% used in infiltration anesthesia could be more effective in reduction or prevention of post-operative endodontic pain compared with lidocaine.