Submucosal Cryotherapy and Anti-inflammatory Drugs for Postoperative Pain Following Root Canal Treatment in Maxillary Molars

October 31, 2026 updated by: hisham elsayed, Suez Canal University

Effect of Submucosal Cryotherapy With or Without Different Anti-inflammatory Drugs on Postoperative Pain and Interleukin-6 Levels in Maxillary Molars With Symptomatic Irreversible Pulpitis: A Randomized Clinical Study

Pain after root canal treatment is a common problem, particularly in teeth with symptomatic irreversible pulpitis, a condition involving severe inflammation of the tissue inside the tooth. Submucosal cryotherapy, which involves applying cold saline through an injection near the affected tooth, may help reduce postoperative pain and inflammation. Anti-inflammatory medications, such as diclofenac sodium and dexamethasone, may also provide pain relief.

This randomized clinical trial aims to evaluate the effects of submucosal cryotherapy, alone or combined with anti-inflammatory medications, on postoperative pain and interleukin-6 (IL-6) levels in patients undergoing root canal treatment of upper molars with symptomatic irreversible pulpitis.

A total of 90 adult patients will be randomly assigned to six groups: local anesthesia alone, cryotherapy with anesthesia, diclofenac sodium with anesthesia, dexamethasone with anesthesia, cryotherapy combined with diclofenac sodium, or cryotherapy combined with dexamethasone. All participants will undergo standardized single-visit root canal treatment.

Postoperative pain will be evaluated during the first 72 hours after treatment. IL-6, a substance involved in inflammation, will be measured in blood samples collected from the dental pulp during treatment. The need for additional pain medication and the occurrence of postoperative flare-ups will also be assessed.

The study seeks to determine whether combining submucosal cryotherapy with anti-inflammatory medications provides greater postoperative pain relief than individual interventions or standard care alone.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Egypt
    • Ismailia Governorate
      • Ismailia, Ismailia Governorate, Egypt, 41522
        • Endodontics Department, Faculty of Dentistry, Suez Canal University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patients aged 21-50 years.
  • Maxillary first or second molars diagnosed with symptomatic irreversible pulpitis.
  • Teeth with mature roots and normal apical tissues or without radiographic evidence of apical pathosis.
  • Vital teeth exhibiting an exaggerated and lingering response to thermal stimuli.
  • Patients experiencing moderate to severe preoperative pain.
  • Patients classified as American Society of Anesthesiologists (ASA) physical status I or II.
  • Teeth considered restorable and suitable for rubber dam isolation.

Exclusion Criteria:

  • Patients with known hypersensitivity or allergy to articaine, diclofenac sodium, dexamethasone, or any materials used in the study.
  • Patients who have received analgesics, anti-inflammatory drugs, corticosteroids, or antibiotics within the preceding 48-72 hours.
  • Pregnant or lactating women.
  • Medically compromised patients or those receiving immunosuppressive therapy.
  • Teeth with periapical lesions, swelling, sinus tracts, tenderness to percussion, or symptomatic apical periodontitis.
  • Previously initiated or previously treated teeth.
  • Teeth with periodontal pockets, root resorption, calcified canals, or non-restorable coronal structures.
  • Cases involving procedural complications, including perforation, instrument separation, or inability to complete root canal treatment according to the standardized protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Anesthesia Alone (Control Group)

Participants will receive local anesthesia using one carpule of 4% articaine hydrochloride with epinephrine 1:100,000 administered by buccal infiltration, with supplemental palatal infiltration if needed. Standardized single-visit root canal treatment will be performed without additional submucosal cryotherapy or anti-inflammatory drug injections.
Drug: Articaine Hydrochloride With Epinephrine

Local anesthesia will be administered using one carpule of 4% articaine hydrochloride with epinephrine 1:100,000 by buccal infiltration before single-visit root canal treatment. Supplemental palatal infiltration will be provided if needed, and any additional anesthetic administration will be recorded. This standard anesthetic regimen will be used in all six study groups.
Experimental: Submucosal Cryotherapy With Anesthesia

Participants will receive standard local anesthesia followed by a single submucosal injection of 1 mL cold normal saline (2-5°C) into the buccal vestibule adjacent to the affected maxillary molar before standardized single-visit root canal treatment.
Drug: Articaine Hydrochloride With Epinephrine

Local anesthesia will be administered using one carpule of 4% articaine hydrochloride with epinephrine 1:100,000 by buccal infiltration before single-visit root canal treatment. Supplemental palatal infiltration will be provided if needed, and any additional anesthetic administration will be recorded. This standard anesthetic regimen will be used in all six study groups.

Procedure: Submucosal Cryotherapy

Submucosal cryotherapy will be performed through a single injection of 1 mL sterile normal saline cooled to 2-5°C into the buccal vestibule adjacent to the affected maxillary molar before root canal treatment. The intervention is intended to provide localized cooling to reduce postoperative inflammation and pain. Cryotherapy will be administered alone or in combination with an anti-inflammatory drug according to group allocation.
Experimental: Diclofenac Sodium With Anesthesia

Participants will receive standard local anesthesia followed by a single submucosal injection of 1 mL diclofenac sodium (25 mg/mL; total dose 25 mg) into the buccal vestibule adjacent to the affected maxillary molar before standardized single-visit root canal treatment.
Drug: Articaine Hydrochloride With Epinephrine

Local anesthesia will be administered using one carpule of 4% articaine hydrochloride with epinephrine 1:100,000 by buccal infiltration before single-visit root canal treatment. Supplemental palatal infiltration will be provided if needed, and any additional anesthetic administration will be recorded. This standard anesthetic regimen will be used in all six study groups.

Drug: Diclofenac Sodium

Diclofenac sodium will be administered as a single preoperative submucosal injection of 1 mL at a concentration of 25 mg/mL (total dose: 25 mg) into the buccal vestibule adjacent to the affected maxillary molar. It will be administered alone or in combination with submucosal cryotherapy according to group allocation to evaluate its effects on postoperative pain and inflammatory response.
Experimental: Dexamethasone With Anesthesia

Participants will receive standard local anesthesia followed by a single submucosal injection of 1 mL dexamethasone sodium phosphate (4 mg/mL; total dose 4 mg) into the buccal vestibule adjacent to the affected maxillary molar before standardized single-visit root canal treatment.
Drug: Articaine Hydrochloride With Epinephrine

Local anesthesia will be administered using one carpule of 4% articaine hydrochloride with epinephrine 1:100,000 by buccal infiltration before single-visit root canal treatment. Supplemental palatal infiltration will be provided if needed, and any additional anesthetic administration will be recorded. This standard anesthetic regimen will be used in all six study groups.

Drug: Dexamethasone Sodium Phosphate

Dexamethasone sodium phosphate will be administered as a single preoperative submucosal injection of 1 mL at a concentration of 4 mg/mL (total dose: 4 mg) into the buccal vestibule adjacent to the affected maxillary molar. It will be administered alone or in combination with submucosal cryotherapy according to group allocation to evaluate its effects on postoperative pain and inflammatory response.
Experimental: Submucosal Cryotherapy With Diclofenac Sodium

Participants will receive standard local anesthesia followed by submucosal administration of cold normal saline (1 mL at 2-5°C) and diclofenac sodium (1 mL at 25 mg/mL) into the buccal vestibule adjacent to the affected maxillary molar before standardized single-visit root canal treatment. The interventions will be administered separately or sequentially according to the finalized study protocol.
Drug: Articaine Hydrochloride With Epinephrine

Local anesthesia will be administered using one carpule of 4% articaine hydrochloride with epinephrine 1:100,000 by buccal infiltration before single-visit root canal treatment. Supplemental palatal infiltration will be provided if needed, and any additional anesthetic administration will be recorded. This standard anesthetic regimen will be used in all six study groups.

Procedure: Submucosal Cryotherapy

Submucosal cryotherapy will be performed through a single injection of 1 mL sterile normal saline cooled to 2-5°C into the buccal vestibule adjacent to the affected maxillary molar before root canal treatment. The intervention is intended to provide localized cooling to reduce postoperative inflammation and pain. Cryotherapy will be administered alone or in combination with an anti-inflammatory drug according to group allocation.

Drug: Diclofenac Sodium

Diclofenac sodium will be administered as a single preoperative submucosal injection of 1 mL at a concentration of 25 mg/mL (total dose: 25 mg) into the buccal vestibule adjacent to the affected maxillary molar. It will be administered alone or in combination with submucosal cryotherapy according to group allocation to evaluate its effects on postoperative pain and inflammatory response.
Experimental: Submucosal Cryotherapy With Dexamethasone

Participants will receive standard local anesthesia followed by submucosal administration of cold normal saline (1 mL at 2-5°C) and dexamethasone sodium phosphate (1 mL at 4 mg/mL) into the buccal vestibule adjacent to the affected maxillary molar before standardized single-visit root canal treatment. The interventions will be administered separately or sequentially according to the finalized study protocol.
Drug: Articaine Hydrochloride With Epinephrine

Local anesthesia will be administered using one carpule of 4% articaine hydrochloride with epinephrine 1:100,000 by buccal infiltration before single-visit root canal treatment. Supplemental palatal infiltration will be provided if needed, and any additional anesthetic administration will be recorded. This standard anesthetic regimen will be used in all six study groups.

Procedure: Submucosal Cryotherapy

Submucosal cryotherapy will be performed through a single injection of 1 mL sterile normal saline cooled to 2-5°C into the buccal vestibule adjacent to the affected maxillary molar before root canal treatment. The intervention is intended to provide localized cooling to reduce postoperative inflammation and pain. Cryotherapy will be administered alone or in combination with an anti-inflammatory drug according to group allocation.

Drug: Dexamethasone Sodium Phosphate

Dexamethasone sodium phosphate will be administered as a single preoperative submucosal injection of 1 mL at a concentration of 4 mg/mL (total dose: 4 mg) into the buccal vestibule adjacent to the affected maxillary molar. It will be administered alone or in combination with submucosal cryotherapy according to group allocation to evaluate its effects on postoperative pain and inflammatory response.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Postoperative Pain Intensity Assessed Using the Numeric Rating Scale (NRS)
Time Frame: At 6, 12, 24, 48, and 72 hours after root canal treatment.

Postoperative pain intensity will be assessed using an 11-point Numeric Rating Scale (NRS), ranging from 0 (no pain) to 10 (worst imaginable pain). Higher scores indicate greater pain intensity. Participants will record their pain intensity at predefined postoperative intervals, and NRS scores will be compared among the six study groups.
At 6, 12, 24, 48, and 72 hours after root canal treatment.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Interleukin-6 (IL-6) Levels in Pulpal Blood
Time Frame: During root canal treatment, immediately after access cavity opening (single intraoperative sample).

Interleukin-6 (IL-6) levels will be measured in pulpal blood samples collected under aseptic conditions after access cavity opening during root canal treatment. Samples will be stored at -20°C and analyzed using enzyme-linked immunosorbent assay (ELISA). IL-6 levels will be compared among the six study groups to evaluate the local inflammatory response.
During root canal treatment, immediately after access cavity opening (single intraoperative sample).
Incidence of Postoperative Flare-Up
Time Frame: Within 72 hours after root canal treatment.

The occurrence of postoperative flare-up following single-visit root canal treatment will be recorded. The number and percentage of participants experiencing flare-up will be determined and compared among the six study groups.
Within 72 hours after root canal treatment.
Incidence of Postoperative Rescue Analgesic Intake
Time Frame: Within 72 hours after root canal treatment.

Participants will be instructed to avoid taking analgesics unless necessary. Any postoperative rescue analgesic intake will be recorded. The number and percentage of participants requiring rescue analgesics will be compared among the six study groups.
Within 72 hours after root canal treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Suez Canal University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 15, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 15, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 15, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 31, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 5, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1160/2026

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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