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

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: Not yet recruiting
• Conditions: Pulpitis
• Intervention / Treatment: Drug: Articaine Hydrochloride With Epinephrine; Procedure: Submucosal Cryotherapy; Drug: Diclofenac Sodium; Drug: Dexamethasone Sodium Phosphate

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hisham E El- Sayed, MSc; Phone Number: +2 0 10 92192763; Email: hesham_elsayed@dent.suez.edu.eg

Study Locations

• Egypt
  • Ismailia Governorate
    • Ismailia, Ismailia Governorate, Egypt, 41522
      • Endodontics Department, Faculty of Dentistry, Suez Canal University
      • Contact: Hisham E El- Sayed, MSc; Phone Number: +2 0 10 92192763; Email: hesham_elsayed@dent.suez.edu.eg

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
Postoperative Pain Intensity Assessed Using the Numeric Rating Scale (NRS)	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

Outcome Measure	Measure Description	Time Frame
Interleukin-6 (IL-6) Levels in Pulpal Blood	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	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	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

• Sponsor: Suez Canal University

Study record dates

Study Major Dates

• Study Start (Estimated): November 15, 2026
• Primary Completion (Estimated): November 15, 2027
• Study Completion (Estimated): November 15, 2027

Study Registration Dates

• First Submitted: October 31, 2026
• First Submitted That Met QC Criteria: October 31, 2026
• First Posted (Actual): November 5, 2026

Study Record Updates

• Last Update Posted (Actual): November 5, 2026
• Last Update Submitted That Met QC Criteria: October 31, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Interleukin-6; Root Canal Treatment; Diclofenac Sodium; Postoperative Pain Management; Symptomatic Irreversible Pulpitis; Endodontic Pain; Submucosal Cryotherapy; Dexamethasone Sodium Phosphate
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Dental Pulp Diseases; Tooth Diseases; Pulpitis; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Alcohols; Amino Alcohols; Ethanolamines; Acids, Carbocyclic; Thiophenes; Biogenic Monoamines; Biogenic Amines; Catecholamines; Phenylacetates; Epinephrine; Diclofenac; Carticaine; dexamethasone 21-phosphate
• Other Study ID 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