Diagnostic is of particular importance in endodontics because of the pulpal sensibility tests that can be the deciding factor between a conservative monitoring and an irreversible treatment [1]. Unlike other specialties where refinement of diagnosis can be performed without much impact on therapy, a missed diagnosis of pulp sensibility can result in over treatment of a vital tooth with root canal or under treatment of a tooth with irreversible pulpitis. This is further improved by the fact that sensibility testing is already an indirect measure of actual pulpal vascular perfusion, which is the actual determinant of vitality. If the error margin is enlarged, then only because of pre-test administration of an analgesic by pharmacologically induced means other than the above [2]. The pharmacodynamics of standard analgesics indicate that there are possible diagnostic interference mechanisms. NSAIDs inhibit the synthesis of the noxious substances (prostaglands) which facilitate the sensitization of peripheral nociceptors and so reduce the transmission of the noxious stimuli generated during testing of cold or electric pulps [3]. Even though it is centrally acting, it is still possible that paracetamol can affect the perception threshold by the serotonergic and endocannabinoid pathways of modulation. Opioids given to patients with dental pain can have a significant change in the level of pain recognition in dorsal horn and brainstem relay nuclei. Even less intense OTC treatments may diminish the amplitude or latency of the pulp test response, especially in the borderline or early pulpal pathological cases where the excitability of the nerves is already lowered [4].

The other practical issue is that analgesics are often administered prior to the manifestation of symptoms to a patient requiring care and not after. Patients seldom realise that several hours before the consultation, patients have taken the medicines, which still have an observable effect on the diagnostics. The interpretation is speculative since the clinician can hardly know the precise dose, the time and the type of medications that have been taken [5]. Two teeth with the same pathology, but that will exhibit opposite test responses, just because the pharmacologic condition of the sensory system of the patient at the time of testing is different. The second dimension of uncertainty is due to variability between different drugs. All analgesics do not influence sensibility to the same degree [6]. For example, NSAIDs may be able to decrease thermal response but increase the reactivity of electric pulps, and centrally acting agents may be able to do the opposite or both. Regimens containing a combination, e.g. ibuprofen and paracetamol or NSAIDs and opioids, can either be additive or synergistic in perception. There is a lack of standards on which clinicians can rely to extrapolate any study or drug into clinical practice without conducting head-to-head comparative studies in standardized conditions [7]. The most frequent symptom for which a patient visits the dentist is pain. Patients often use analgesics before their dental consultation to reduce pain from pulpitis, periapical pathology, trauma or other dental diseases [8]. Non-steroidal anti-inflammatory drugs (NSAIDs), including ibuprofen and diclofenac, as well as acetaminophen (paracetamol), are some of the most prescribed and self-administered analgesics around the world [9]. All these drugs work by inhibiting the synthesis of prostaglandins and inhibiting inflammatory pathways to decrease pain perception and inflammation [10]. However, there is clinical interest in their effect on the responses of the pulpal nerves and in the diagnostic value of the sensibility tests. The effect of preoperatively giving pain medication on pulpal sensibility testing has been a subject of several studies, which unfortunately show inconsistent results [11]. A few researchers have reported decreased responsiveness to thermal and electrical stimulation after taking NSAIDs and others have reported no significant changes in test results. These conflicting results might be explained by differences in study design, the type of analgesic used, the dose given, when it was given, and what method was used to test it. Furthermore, the vast majority of the literature has focused on small populations and there is little information on the comparative effects of the analgesics in common use on pulpal sensibility testing [12].

Objectives

The main objective of the study is:

• To evaluate the effect of commonly used analgesics on the diagnostic response patterns elicited by standard pulpal sensibility tests.

This Randomized, double-blind, placebo-controlled trial study was conducted at School of Dentistry Islamabad from September 2025 to March 2025. Data were collected from 184 participants. Sample size was calculated using WHO calculator using a 95% confidence level and 80% power to detect a mean difference of 1.5 units in EPT threshold values between groups, assuming a standard deviation of 3.0 [1]. The eligible individuals who met the inclusion and exclusion criteria were recruited by the consecutive sampling technique, which is a non-probability sampling technique. Included were healthy individuals, adults aged 18–40 years, having intact maxillary central incisors with no caries and with normal baseline responses to pulpal sensibility testing. Those who took any analgesic, sedative or psychotropic medicines in the last 24 hours were not included. This included teeth with restorations or fractures, teeth with developmental defects or periapical pathology. Systemic diseases that affect pain perception, allergy or contraindication to the drugs tested, pregnancy, lactation or chronic use of analgesics, corticosteroids or psychotropic drugs were not taken into consideration.

Data Collection Procedure

After approval from the Institutional Ethical Review Committee, eligible participants were recruited and informed consent was obtained. Using a computer-generated sequence of random numbers, the participants were randomly assigned to one of four equal groups. Allocation concealment was ensured by preparing opaque, consecutively numbered, and sealed envelopes by an independent researcher. Group allocation and both the examiner and the subject were blinded to pulpal sensibility tests. Identical-appearing study drugs and placebo capsules were prepared by the institutional pharmacy department. The participants were given either ibuprofen 400 mg or Paracetamol 1000 mg. The medications were given orally to each participant, supervised by them with 100 mL of water. To standardise, one complete maxillary central incisor was selected for each participant for testing. Baseline pulpal sensibility responses were taken prior to drug administration and post drug testing was done one hour after drug administration.

1,1,1,2-tetrafluoroethane spray was used in the cold test to coat a cotton pellet, which was then set on the middle surface of the chosen tooth. The participants were asked to raise their hand when they first felt cold sensation or pain. A digital stopwatch was used to measure the time lag, which was classified as positive, delayed or non-response. Electric pulp testing was done on a digital pulp test. The electrode was put on the middle third of the labial surface of the tooth and conductive gel applied. The intensity of the stimulus was gradually increased until the participant felt a tingling or painful sensation for the first time, and the value of the stimulus displayed was then recorded. All tests were performed twice and mean value used for analysis. The main outcome measure was changes in electric pulp threshold values before and after administration of the analgesic. Secondary outcome variables were the change in cold test response time and response category.

Statistical Analysis

Data were analysed with SPSS version 26.0. Quantitative variables were presented as mean ± standard deviation and frequencies and percentages for categorical variables. Data distribution was tested for normality using Shapiro–Wilk test. The pre- and post-intervention comparisons within the groups were conducted by paired t-tests and inter-group comparisons were conducted by one-way ANOVA with Tukey's post hoc test. The categorical variables were analyzed by chi-square test. A p value less than 0.05 was deemed to be statistically significant.

Data were collected from 184 participants, with 92 participants in the paracetamol group and 92 participants in the ibuprofen group. The mean age was 27.9 ± 5.6 years in the paracetamol group and 27.4 ± 5.2 years in the ibuprofen group. Gender distribution was balanced between both groups. All participants had intact, caries-free maxillary central incisors with no restoration or fracture, normal baseline cold and EPT responses, and no analgesic use in the previous 24 hours.

Table 1. Baseline Demographic Characteristics of Participants (N = 184)

The ibuprofen group showed a clear increase in electric pulp test threshold values from 21.4 ± 4.8 at baseline to 24.9 ± 5.2 after drug administration, with a mean change of 3.5 and a statistically significant p-value of <0.001. In comparison, the paracetamol group showed only a mild increase from 21.7 ± 4.6 to 22.8 ± 4.9, with a mean change of 1.1, which was not statistically significant (p=0.08).

Table 2. Electric Pulp Test Threshold Values Before and After Analgesic Administration

The mean change in EPT threshold was significantly greater in the ibuprofen group compared with the paracetamol group. Ibuprofen produced a 2.4-unit greater increase in EPT threshold values than paracetamol, and this difference was statistically significant (p=0.012).

Table 3. Comparison of Mean Change in EPT Threshold Values between Groups

Cold test response time also increased more prominently in the ibuprofen group. The response time increased from 1.42 ± 0.36 seconds to 1.91 ± 0.44 seconds, with a mean change of 0.49 seconds and a statistically significant p-value of <0.001. In contrast, the paracetamol group showed a smaller increase from 1.45 ± 0.34 seconds to 1.58 ± 0.39 seconds, with a mean change of 0.13 seconds, which was not statistically significant (p=0.06).

Table 4. Cold Test Response Time Before and After Analgesic Administration

After drug administration, positive cold test response was observed in 80 (87.0%) participants in the paracetamol group and 64 (69.6%) participants in the ibuprofen group. Delayed response was more frequent in the ibuprofen group, occurring in 28 (30.4%) participants, compared with 12 (13.0%) participants in the paracetamol group. No complete loss of response was observed in either group. The difference in cold test response categories between the two groups was statistically significant (p=0.008).

Table 5. Cold Test Response Categories after Drug Administration

The present study aimed to assess the effect of some analgesics commonly used on pulpal sensibility tests among healthy adult subjects. Diclofenac and ibuprofen were found to significantly elevate the EPT threshold values and delay EPT and CTR response time, respectively, while Paracetamol had only slight statistically non-significant changes. Placebo had no significant impact. These results indicate that NSAIDs can temporarily decrease the sensibility responsiveness of the pulps and could affect the results of pulpal sensibility testing. The electric pulp testing is based on stimulation of the nerve fibers in the pulp, primarily A-delta fibers. In this study, those who received diclofenac and ibuprofen needed higher values of electrical stimuli after the drugs were administered than before. This means that after taking these NSAIDs, the sensitivity of the pulp reduces [13]. The proposed mechanism is that NSAIDs block cyclooxygenase enzymes, and prostaglandin synthesis, thus reducing peripheral sensitization of nociceptors. This means that perception of pain may be lessened, and a higher intensity stimulus may be needed to get a response [14].

Results of the cold tests were similar. Diclofenac had the longest cold response time and ibuprofen the second longest. This indicates that NSAIDs could influence the patient's feeling with thermal stimulation. None of the participants had a complete absence of response, however, suggesting that these may only delay or diminish response of the pulpal tissues. In the clinical setting, this is significant as recent use of analgesics can result in less or a delayed response when using diagnostic testing, and can also result in more misinterpretation, particularly in border-line cases [15]. There were only slight changes in electric pulp testing and cold testing with Paracetamol. This may be due to the lower peripheral anti-inflammatory activity of paracetamol compared to the NSAIDs and the effect being exerted mainly through central pathways regulating pain, rather than through peripheral ones. Thus, its effect on pulpal sensibility seems to be less significant in comparison to ibuprofen and diclofenac. These results indicated that NSAIDs are more likely to have an effect on chairside pulpal sensibility tests over paracetamol [16-18].

The present results have clinical implications in the diagnostics of endodontic diseases. The results of pulpal sensibility tests vary from patient to patient and are therefore subjective, so any medication that alters the patient's perception of pain will have an impact on the accuracy of the test. For this reason, dentists need to know the use of analgesics prior to the use of cold tests or electric pulp tests [19,20]. Test results must be used with caution in patients who have recently used NSAIDs, and must be evaluated in the context of other available tests, history and clinical findings, and radiographs [21]. There are a number of limitations in the study. The sample consisted of healthy adult volunteers with intact central incisors of the maxilla and may not be applicable to patients having diseased or inflamed pulps. The long-term or repeated use of analgesics was not examined, only the single-dose effects were studied. The answer was also subjective and based on patients perception. Additional research is suggested that would involve multiple time points of pulpal diagnostic testing after administration of an analgesic, larger sample size, and symptomatic teeth of various types to evaluate the clinical effects of analgesics on diagnostic testing of the pulp.

Commonly used analgesics exert varying effects on pulpal sensibility test responses. Ibuprofen significantly reduced pulpal sensory responsiveness compared with paracetamol, as shown by increased EPT threshold values, prolonged cold test response time, and a higher frequency of delayed cold responses. Paracetamol showed only minimal and statistically non-significant effects. Therefore, recent ibuprofen use may influence the interpretation of pulpal sensibility tests and should be considered during endodontic diagnosis.

1. Sooratgar A, Khavanin N, Dibaji F, Asadi Y, Kharazifard M. Evaluation of the Effect of Common Analgesics on Pulpal Sensibility Tests: A Clinical Trial. J Endod. 2023 Apr;49(4):362-368. doi: 10.1016/j.joen.2023.01.003. Epub 2023 Jan 16. PMID: 36657522.
2. Hazard ML, Wicker C, Qian F, Williamson AE, Teixeira FB. Accuracy of cold sensibility testing on teeth with full-coverage restorations: a clinical study. Int Endod J. 2021 Jul;54(7):1008-1015. doi: 10.1111/iej.13490. Epub 2021 Feb 25. PMID: 33550601.
3. Eslambol Nassaj A, Nekouei AH, Fereidooni R, Kamyabi H, Pardakhty A, Shahravan A. Comparative Efficacy of Analgesics for Pain Relief in Patients with Symptomatic Irreversible Pulpitis Prior to Emergency Endodontic Treatment: A Randomized Controlled Trial. Iran Endod J. 2023;18(4):194-201. doi: 10.22037/iej.v18i4.35469. PMID: 37829826; PMCID: PMC10565996.
4. Kazemipoor M, Vatanchian MK, Jambarsang S, Owlia F. Evaluation of the Response to Pulpal Sensibility Tests (Cold, EPT) in Anemic and Healthy Women. Int J Dent. 2022 Jun 18;2022:3518817. doi: 10.1155/2022/3518817. PMID: 35761967; PMCID: PMC9233581.
5. Singh NR, Mishra L, Pawar AM, Kurniawati N, Wahjuningrum DA. 2022. Comparative evaluation of the effect of two pulpal medicaments on pain and bleeding status of mandibular molars with irreversible pulpitis post-failure of inferior alveolar nerve block: a double-blind, randomized, clinical trial. PeerJ 10:e13397 https://doi.org/10.7717/peerj.13397
6. Owlia, F., Mahmoudzade, N., Modaresi, J. et al. Evaluation of the response to electric pulp testing in multiple sclerosis patients without a history of trigeminal neuralgia: a case-control study. BMC Neurol 21, 403 (2021). https://doi.org/10.1186/s12883-021-02416-0
7. Modaresi J, Afkhami-Ardekani M, Mokhtari F, Salmani-Qahyazi A, Amirzade-Iranaq MH. The comparison of tooth pulp electrical threshold in patients with type II uncontrolled diabetes and healthy subject. Iran J Diabetes Obes. 2017;9(1):20–4.
8. Sooratgar A, Khavanin N, Dibaji F, Asadi Y, Kharazifard M. Evaluation of the Effect of Common Analgesics on Pulpal Sensibility Tests: A Clinical Trial. J Endod. 2023 Apr;49(4):362-368. doi: 10.1016/j.joen.2023.01.003. Epub 2023 Jan 16. PMID: 36657522.
9. Hazard ML, Wicker C, Qian F, Williamson AE, Teixeira FB. Accuracy of cold sensibility testing on teeth with full-coverage restorations: a clinical study. Int Endod J. 2021 Jul;54(7):1008-1015. doi: 10.1111/iej.13490. Epub 2021 Feb 25. PMID: 33550601.
10. Singh NR, Mishra L, Pawar AM, Kurniawati N, Wahjuningrum DA. Comparative evaluation of the effect of two pulpal medicaments on pain and bleeding status of mandibular molars with irreversible pulpitis post-failure of inferior alveolar nerve block: a double-blind, randomized, clinical trial. PeerJ. 2022 May 13;10:e13397. doi: 10.7717/peerj.13397. PMID: 35586130; PMCID: PMC9109695.
11. Arora, T., Singla, R., Gill, G.S. et al. Diagnostic accuracy of combined pulp sensibility tests for detecting post-anesthetic pulpal anesthesia in mandibular molars with symptomatic irreversible pulpitis. Sci Rep (2026). https://doi.org/10.1038/s41598-026-49432-z
12. Eslambol Nassaj A, Nekouei AH, Fereidooni R, Kamyabi H, Pardakhty A, Shahravan A. Comparative Efficacy of Analgesics for Pain Relief in Patients with Symptomatic Irreversible Pulpitis Prior to Emergency Endodontic Treatment: A Randomized Controlled Trial. Iran Endod J. 2023;18(4):194-201. doi: 10.22037/iej.v18i4.35469. PMID: 37829826; PMCID: PMC10565996.
13. Iranmanesh F, Parirokh M, Haghdoost AA, Abbott PV. Effect of corticosteroids on pain relief following root canal treatment: a systematic review. Iran Endod J. 2017;12(2):123-130. doi:10.22037/iej.2017.26
14. Shadmehr E, Hashemi S, Hashemi SS, Chung YJ, Goudarzi A, Khademi A. The effect of adding clonidine to articaine and epinephrine on post-treatment pain: a randomized clinical trial study. Iran Endod J. 2021;16(4):210-216. doi:10.22037/iej.v16i4.33555
15. Shafie L, Esmaili S, Parirokh M, Pardakhti A, Nakhaee N, Abbott PV, et al. Efficacy of pre-medication with ibuprofen on post-operative pain after pulpotomy in primary molars. Iran Endod J. 2018;13(2):216-220. doi:10.22037/iej.v13i2.16624
16. Mokhtari F, Yazdi K, Mahabadi AM, Modaresi SJ, Hamzeheil Z. Effect of premedication with indomethacin and ibuprofen on postoperative endodontic pain: a clinical trial. Iran Endod J. 2016;11(1):57-62. doi:10.7508/iej.2016.01.011
17. Porreca F, Ossipov MH. Nausea and vomiting side effects with opioid analgesics during treatment of chronic pain: mechanisms, implications, and management options. Pain Med. 2009;10(4):654-662. doi:10.1111/j.1526-4637.2009.00583.x
18. Schug SA, Zech D, Grond S. Adverse effects of systemic opioid analgesics. Drug Saf. 1992;7(3):200-213. doi:10.2165/00002018-199207030-00005
19. Eghbal MJ, Asgary S, Baglue RA, Parirokh M, Ghoddusi J. MTA pulpotomy of human permanent molars with irreversible pulpitis. Aust Endod J. 2009;35(1):4-8. doi:10.1111/j.1747-4477.2009.00166.x
20. Gori NA, Patel MC, Bhatt R, Joshi KR, Patel FC, Choksi KB. Clinical Assessment of Preemptive Analgesia on Success of Pulpal Anesthesia and Postendodontic Pain in Children with Irreversible Pulpitis: A Randomized Comparative Study. Int J Clin Pediatr Dent. 2024 Jan;17(1):72-78. doi: 10.5005/jp-journals-10005-2741. PMID: 38559853; PMCID: PMC10978509.
21. d F. C. Souza, E. B. A. F. )omaz, and C. P. S. Costa, “Healthy dental pulp oxygen saturation rates in subjects with homozygous sickle cell anemia: a cross-sectional study nested in a cohort,” Journal of Endodontics, vol. 43, no. 12, pp. 1997–2000, 2017