|Year : 2016 | Volume
| Issue : 4 | Page : 128-132
Effect of Local and Application of Amitriptyline and Imipramine on Teeth with Irreversible Pulpitis Failed Pulpal Anesthesia: A Randomized, Double-blind, Controlled Trial
Mohsen Aminsobhani1, Naghmeh Meraji2, Abdollah Ghorbanzadeh2, Majid Ajami1, Seied Ali Seiedi Hoseini3, Mohammad J Kharazifard4
1 Department of Endodontics, School of Dentistry, AJA University of Medical Sciences, Tehran; Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
3 Private Practice, Tehran, Iran
4 Dental Research Center, School of Dentistry, Tehran University of Medical Sciences, Tehran, Iran
|Date of Web Publication||21-Dec-2016|
Department of Endodontics, School of Dentistry, Tehran University of Medical Sciences, Tehran
Source of Support: None, Conflict of Interest: None
Clinical trial registration IRCT201110317963N1
Introduction: To evaluate the analgesic effect of amitriptyline and imipramine after local application on the dentine of “hot teeth” with failed pulpal anesthesia.
Materials and Methods: This study was a randomized, double-blind clinical trial that was performed on 33 consenting adult patients who were referred to us and had mandibular molars diagnosed with symptomatic irreversible pulpitis and experienced pain during access cavity preparation after receiving successful inferior alveolar nerve block with lidocaine. Either amitriptyline, imipramine or placebo was administered locally on the exposed dentine of the teeth. Pre and post-application pain levels were evaluated by McGill visual analog scale.
Results: Amitriptyline significantly reduced the pain experienced by patients (P = 0.032). Imipramine also reduced the experienced pain but the pain relief was not statistically significant when compared with the placebo.
Conclusion: Local administration of amitriptyline on exposed dentine can reduce the pain experienced by patients with a “hot tooth.”
Keywords: Amitriptyline, imipramine, pain management, pulpitis
|How to cite this article:|
Aminsobhani M, Meraji N, Ghorbanzadeh A, Ajami M, Hoseini SS, Kharazifard MJ. Effect of Local and Application of Amitriptyline and Imipramine on Teeth with Irreversible Pulpitis Failed Pulpal Anesthesia: A Randomized, Double-blind, Controlled Trial. Dent Hypotheses 2016;7:128-32
|How to cite this URL:|
Aminsobhani M, Meraji N, Ghorbanzadeh A, Ajami M, Hoseini SS, Kharazifard MJ. Effect of Local and Application of Amitriptyline and Imipramine on Teeth with Irreversible Pulpitis Failed Pulpal Anesthesia: A Randomized, Double-blind, Controlled Trial. Dent Hypotheses [serial online] 2016 [cited 2019 Jun 19];7:128-32. Available from: http://www.dentalhypotheses.com/text.asp?2016/7/4/128/195969
| Introduction|| |
The term “hot tooth” is referred to a tooth that has been diagnosed with irreversible pulpitis, with spontaneous, moderate-to-severe pain. Clinical studies have shown a higher failure rate in pulpal anesthesia with the inferior alveolar nerve block occurring 44–81% of the times in these teeth., Failure of pulpal anesthesia is a major obstacle in their root canal treatment. Various clinical studies have been performed with the aim of increasing the success rate of pulpal anesthesia during endodontic procedures in these situations. Some applied various anesthetic techniques and/or solutions,[3-6] and some investigated the effect of pretreatment with different analgesics., However, none of these supplementary interventions were 100% successful in achieving complete pulpal anesthesia.
Some studies have shown that tricyclic antidepressants (TCAs), such as amitriptyline and imipramine, are effective in controlling pain., For instance, imipramine is used for controlling painful peripheral neuropathies, post-herpetic neuralgia, and central post-stroke pain., Chen et al. showed that intrathecal imipramine produced spinal anesthetic effects that are more potent and longer than that of lidocaine.
Amitriptyline is commonly used for pain management in a variety of chronic and neuropathic pain syndromes, chronic fatigue syndrome, migraine, persistent arm pain, and atypical facial pain.,, Furthermore, TCAs can have an analgesic effect when applied topically; this effect is produced by peripheral mechanisms. Movassaghian et al. developed amitriptyline buccoadhesive tablets with sufficient analgesic effects in the buccal mucosal membrane of the oral cavity.
Considering the analgesic effects of amitriptyline and imipramine, the aim of this study was to evaluate the analgesic effect of these TCAs after local application on the dentine of “hot teeth” with failed pulpal anesthesia.
The null hypothesis was that both drugs would decrease the pain experienced by patients.
| Materials and Methods|| |
The minimal sample size of 8 was calculated for each group by repeated measures analysis of variance (ANOVA) using PASS 11 software (NCSS Statistical Software, Utah, USA) considering alpha = 0.05 and beta = 0.1 for a between-subject factor with three levels and mean standard deviation of 2.5 and means matrix based on 5 pilot participants. The amount of error term visual analog scale (VAS) in each group compared to the mean was evaluated by one-sample Kolmogrov Smirnov and no statistically significant difference was seen between the distribution of the variable and norm (P > 0.05).
10 mg amitriptyline (Darou Pakhsh, Tehran, Iran), 10 mg imipramine (Sobhan Pharma Group, Tehran, Iran) tablets, and starch powder (as placebo) were used in this study. After removing the colored coating of the tablets, each tablet was ground to a powder form in a mortar and then transferred and stored in an Eppendorf tube so that each tube contained 10 mg of either amitriptyline, imipramine, or starch. The Eppendorf tubes were concealed and coded so that the operating clinician would not be aware of the content of each tube. Each coded tube was assigned to a patient by a person other than the operator by simple randomization.
Thirty-three consenting healthy patients between the ages of 18 and 55 years with no systematic disease who were referred to our private clinic and diagnosed with symptomatic irreversible pulpitis in their mandibular molar teeth were considered in this study.
Patients with a history of hypersensitivity to TCAs, epinephrine or lidocaine were excluded from the study., Furthermore, pregnant or lactating patients and those who had received systemic analgesics 4 to 6, hours prior to the therapeutic procedure were excluded from the study. Among the included patients, those who had experienced pain during access cavity preparation (before pulp exposure) 15 minutes after the administration of an inferior alveolar block injection with lidocaine and 1/80000 epinephrine (Persocaine, Darou Pakhsh, Tehran, Iran) regardless of showing all signs of success block injection, were included as participants in this study.
The pain experienced by patients was evaluated by McGill VAS., This scale consists of a 10 cm (with ten 1 cm units) ruler in length with the left-hand end representing complete painlessness (0) and the right-hand end representing the worst pain imaginable., After measuring the pain experienced by the patient during access cavity preparation (before pulp exposure), an eppendorf tube containing either amitriptyline, imipramine or placebo was randomly assigned for the patient. Therefore, patients were divided into three groups (n = 11) by simple randomization [Table 1] and [Figure 1].
|Table 1 Baseline demographic and clinical characteristics of patients in each group|
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|Figure 1 Patient progress through trial: CONSORT flow chart for this study|
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It should be noted that the operating clinician was blind and unaware of the contents of the tube. The powder in the tube was placed in the tooth cavity and a cotton pellet was placed on it and the patient was told to bite the cotton pellet. The teeth were not isolated by rubber dam and saliva could have come in contact with the cotton pellet, however, a high volume suction was used to prevent any probable swallowing of drugs by the patient. Ten minutes after the application, the clinician started to prepare the access cavity again and during this procedure the pain experienced by the patient was evaluated again. Data were analyzed by one-way ANOVA and Tukey HSD test by Statistical Package for the Social Sciences version 22 software (Microsoft, IL, USA). Differences were considered statistically significant at P < 0.05, when a 95% confidence interval level was obtained.
| Results|| |
One hundred patients were recruited for the study. Sixty were excluded for not meeting inclusion criteria and 7 declined to participate in the study. Thirty-three patients participated in this study. The baseline demographic and clinical characteristics of participants in each group are shown in [Table 1].
The mean pre-application, post-application, and pain relief scores of each experimental group are shown in [Table 2]. According to the results of this study, amitriptyline significantly reduced the pain experienced by patients (P = 0.032). Imipramine also reduced the pain experienced by patient but the pain relief was not statistically significant [Figure 2].
|Table 2 The mean pre-application, post-application, and pain relief scores of each experimental group|
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|Figure 2 The mean ± standard deviation (SD) of pain relief in each experimental group. Different superscript letters represent statistically significant differences (P < 0.05)|
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| Discussion|| |
Numerous inflammatory mediators are present in the inflamed dental pulp. It has been shown that inflammatory mediators of the pulp can activate or sensitize pulpal neurons by interacting with specific receptors, thus altering the activity of neurons. For instance, Bradykinin activates and Prostaglandin E2 sensitizes nociceptors. Allodynia, hyperalgesia, and spontaneous pain are characterizations of peripheral sensitization and activation of nociceptors which occurs during inflammatory situations. The higher failure rate in pulpal anesthesia in the “hot tooth” has been related to the sensitization and activation of peripheral nociceptors.,
In addition, the composition, distribution, level of expression, or activity of voltage-gated sodium channels (VGSCs) expressed on nociceptors is altered due to pulpal tissue injury and inflammation. It has been shown that the activity of tetrodotoxin resistant (TTX-r) sodium channels (Nav1.5, Nav1.8, and Nav1.9) double in inflammatory situations. In addition, these channels are expressed in higher levels in these conditions. TTX-r channels are approximately four times less sensitive to lidocaine. These changes in VGSCs may also have profound correlation with pulpal anesthetic failures in teeth with symptomatic irreversible pulpitis.
According to the results of the current study, amitriptyline significantly reduced the pain experienced by patients. Amitriptyline has an inhibitory effect on VGSCs and reduces the generation and conduction of action potentials in sensory neurons. This TCA has special binding sites near the receptors of local anesthetics on VGSCs., In addition, it has been shown that this substance has the ability to block both Nav1.8 and Nav1.9 TTX-r channels. These mechanisms may contribute to the pain relief experiences subsequent to its local application.
Although imipramine also has an inhibitory effect on VGSCs and both amitriptyline and imipramine have shown longer inhibitory effects on VGSCs than that of bupivacaine, the pain relief experienced by patients after the application of imipramine showed no statistically significant difference to that of the placebo. Both amitriptyline and imipramine are water soluble but imipramine has a higher molecular weight than that of amitriptyline. The molecular weight and size of imipramine may prohibit its diffusion through dentinal tubules, and therefore, may limit its effect on pulpal nociceptors. Further research is required regarding this matter.
| Conclusion|| |
Local application of amitriptyline on the dentine of teeth with inflamed pulpal tissue exhibiting failure in pulpal anesthesia reduces the pain experienced by patients and may be considered as an option for pain relief during access cavity preparation.
Financial support and sponsorship
This study was supported by a grant from Tehran University of Medical Sciences (Grant #15772).Conflicts of interest
There are no conflicts of interest.
This double blinded parallel group randomized clinical trial was approved by the Ethics Committee of Tehran University of Medical Sciences (#90-04-69-15772-49211) and registered in www.irct.ir (IRCT201110317963N1).
| References|| |
Nusstein JM, Reader A, Drum MLocal anesthesia strategies for the patient with a “hot” toothDent Clin North Am20105423747
Matthews R, Drum M, Reader A, Nusstein J, Beck MArticaine for supplemental buccal mandibular infiltration anesthesia in patients with irreversible pulpitis when the inferior alveolar nerve block failsJ Endod2009353436
Bigby J, Reader A, Nusstein J, Beck MAnesthetic efficacy of lidocaine/meperidine for inferior alveolar nerve blocks in patients with irreversible pulpitisJ Endod200733710
Saatchi M, Khademi A, Baghaei B, Noormohammadi HEffect of sodium bicarbonate-buffered lidocaine on the success of inferior alveolar nerve block for teeth with symptomatic irreversible pulpitis: A prospective, randomized double-blind studyJ Endod201541335
Rogers BS, Botero TM, McDonald NJ, Gardner RJ, Peters MCEfficacy of articaine versus lidocaine as a supplemental buccal infiltration in mandibular molars with irreversible pulpitis: A prospective, randomized, double-blind studyJ Endod2014407538
Shetty KP, Satish SV, Kilaru KR, Sardar P, Luke AMComparison of Anesthetic Efficacy between Lidocaine with and without Magnesium Sulfate USP 50% for Inferior Alveolar Nerve Blocks in Patients with Symptomatic Irreversible PulpitisJ Endod2015414313
Nusstein JMPreoperative oral use of Ibuprofen or dexamethasone may improve the anesthetic efficacy of an inferior alveolar nerve block in patients diagnosed with irreversible pulpitisJ Evid Based Dent Pract2013131023
Aggarwal V, Singla M, Kabi DComparative evaluation of effect of preoperative oral medication of ibuprofen and ketorolac on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis: A prospective, double-blind, randomized clinical trialJ Endod2010363758
McQuay H, Tramer M, Nye B, Carroll D, Wiffen P, Moore RA systematic review of antidepressants in neuropathic painPain19966821727
Sudoh Y, Cahoon EE, Gerner P, Wang GKTricyclic antidepressants as long-acting local anestheticsPain20031034955
Cohen SP, Abdi SNew developments in the use of tricyclic antidepressants for the management of painCurr Opin Anesthesiol20011450511
Rasmussen PV, Jensen TS, Sindrup SH, Bach FWTDM-based imipramine treatment in neuropathic painTher Drug Monit20042635260
Chen YW, Shieh JP, Chen JY, Chu CC, Tzeng JI, Wang JJImipramine, Clomipramine and Trimipramine Have Long-acting Spinal Anesthetic EffectsTzu Chi Med J200618913
Goldman RH, Stason WB, Park SK, Kim R, Mudgal S, Davis RB et al.
Low-dose amitriptyline for treatment of persistent arm pain due to repetitive usePain201014911723
McCleane GAntidepressants as analgesicsCNS Drugs20082213956
Movassaghian S, Barzegar-Jalali M, Alaeddini M, Hamedyazdan S, Afzalifar R, Zakeri-Milani P et al.
Development of amitriptyline buccoadhesive tablets for management of pain in dental proceduresDrug Dev Ind Pharm20113784954
Yagiela JAAdverse drug interactions in dental practice:Interactions associated with vasoconstrictors:Part V of a seriesJ Am Dent Assoc19991307019
Moghadamnia AA, Partovi M, Mohammadianfar I, Madani Z, Zabihi E, Hamidi MR et al.
Evaluation of the effect of locally administered amitriptyline gel as adjunct to local anesthetics in irreversible pulpitis painIndian J Dent Res20092036
Ong C, Lirk P, Tan C, Seymour RAn evidence-based update on nonsteroidal anti-inflammatory drugsClin Med Res200751934
DeRuiter JNon-steroidal anti-inflammatory drugs (NSAIDs)Principles of Drug Action20022126
Parirokh M, Ashouri R, Rekabi AR, Nakhaee N, Pardakhti A, Askarifard S et al.
The effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitisJ Endod20103614504
Reader A, Nusstein J, Khan APain Control. Pathways of the pulp200611th edSt. Louis, MoElsevier Mosby90129
Hargreaves KM, Keiser KLocal anesthetic failure in endodonticsEndod Topics200212639
Gibbs JL, Hargreaves KMIngle JI, Bakland LK, Baumgartner JCMechanisms of odontogenic and non-odontogenic pain. Ingle's Endodontics20086th edHamiltonBC Decker Inc37687
Henry MA, Hargreaves KMPeripheral mechanisms of odontogenic painDent Clin North Am2007511944
Coggeshall RE, Tate S, Carlton SMDifferential expression of tetrodotoxin-resistant sodium channels Nav1.8 and Nav1.9 in normal and inflamed ratsNeurosci Lett2004355458
Pancrazio JJ, Kamatchi GL, Roscoe AK, Lynch CInhibition of neuronal Na+channels by antidepressant drugsJ Pharmacol Exp Ther199828420814
Wang GK, Russell C, Wang SYState-dependent block of voltage-gated Na+channels by amitriptyline via the local anesthetic receptor and its implication for neuropathic painPain200411016674
Liang J, Liu X, Zheng J, Yu SEffect of amitriptyline on tetrodotoxin-resistant Nav1. 9 currents in nociceptive trigeminal neuronsMol Pain2013931
Yang YC, Kuo CCInhibition of Na(+) current by imipramine and related compounds:Different binding kinetics as an inactivation stabilizer and as an open channel blockerMol Pharmacol200262122837
Khan MA, Gerner P, Kuo WGAmitriptyline for prolonged cutaneous analgesia in the ratAnesthesiology20029610916
[Figure 1], [Figure 2]
[Table 1], [Table 2]