Postoperative Pain After Endodontic TreatmentCRYO-IRISNCT07889050
Effect of Intracanal Cryotherapy on Pain, Anxiety, and Salivary Irisin After Root Canal Treatment
A study testing Intracanal Cryotherapy and Standard Room-Temperature Irrigation in people with Postoperative Pain After Endodontic Treatment and Dental Anxiety, run by Alanya Alaaddin Keykubat University at 1 site in Turkey (Türkiye).
Trial summary
Some people feel pain after a root canal treatment. This study will test whether intracanal cryotherapy, a final rinse of the tooth with cold sterile saline, can reduce this pain compared with a room-temperature rinse. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Postoperative Pain After Endodontic Treatment, Dental Anxiety, Root Canal Treatment
- What is being tested?
- Intracanal Cryotherapy and Standard Room-Temperature Irrigation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Nov 2026to 15 Feb 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years
- Single-rooted, single-canal mandibular premolar teeth with no previous root -canal treatment
- Asymptomatic apical periodontitis (Periapical Index score ≥ 3)
- Systemically healthy (ASA I-II)
- Signed informed consent form
- Able to be contacted and attend follow-up appointments
- Able to maintain a pain diary
- No use of anti-inflammatory medication within the past 3 months
Who cannot join
- Pregnancy or breastfeeding
- Systemic diseases (diabetes mellitus, cardiovascular disease, renal or hepatic insufficiency)
- Use of immunosuppressive therapy
- Use of corticosteroids or NSAIDs within the past 3 months
- Use of antibiotics within the past 1 month
- Presence of periapical abscess or sinus tract
Show all 19Show fewer
- Vertical root fracture
- Root perforation
- External or internal root resorption
- Canal obstruction in the apical third
- Periodontal disease (presence of pockets deeper than 3 mm)
- Excessive dental hypersensitivity
- Bruxism
- Occlusal trauma
- Mental or psychiatric disorder
- Neurological disease affecting pain perception
- Allergy to paracetamol
- Refusal to participate in the study
- Body mass index above 35 kg/m²
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site
Alanya Alaaddin Keykubat University, Faculty of Dentistry
Antalya, Antalya, 07400
About this study
Official title: Evaluation of Postoperative Pain, Pain Catastrophizing, Dental Anxiety, and Salivary Irisin Levels in Patients With and Without Intracanal Cryotherapy Application During Single-Visit Root Canal Treatment
Some people feel pain after a root canal treatment. This study will test whether intracanal cryotherapy, a final rinse of the tooth with cold sterile saline, can reduce this pain compared with a room-temperature rinse.
Previous studies have suggested that intracanal cryotherapy may reduce pain after root canal treatment. In this study, we will examine its effect in a defined group of patients and explore how it works. We will measure the level of irisin, a substance with reported anti-inflammatory properties, in saliva to see whether cryotherapy changes it. We will also look at whether a person's tendency to worry about pain (pain catastrophizing) changes the effect of cryotherapy on pain, and whether dental anxiety is related to pain after treatment.
Read more
Adults aged 18 to 65 who need root canal treatment on a single-rooted lower premolar tooth will receive standard single-visit treatment. By chance, 100 participants will be placed in a cold-saline group or a room-temperature-saline group. Thirty healthy volunteers will give one saliva sample for comparison. Participants will complete questionnaires before treatment, rate their pain over the 7 days after treatment, and give saliva samples for irisin measurement.
The main questions this study aims to answer are:
Does intracanal cryotherapy lower pain after root canal treatment? Does it change salivary irisin levels? Does pain catastrophizing change the effect of cryotherapy? Is dental anxiety related to pain after treatment?
Read the detailed description
Postoperative pain after root canal treatment remains a common clinical challenge, even when the procedure is performed correctly. Intracanal cryotherapy, a final irrigation of the root canal with cooled sterile saline, has been proposed to reduce postoperative inflammation and pain by slowing local tissue metabolism and limiting the release of inflammatory mediators. Previous studies have reported a pain-reducing effect, but the biological mechanism is not fully understood.
Irisin is a myosine with reported anti-inflammatory properties, and, to our knowledge, its measurement in saliva in the context of endodontic pain has not been previously investigated. Pain catastrophizing has been associated with higher postoperative pain in previous studies, but it remains unclear whether it influences the effect of cryotherapy on pain. This study addresses cryotherapy, salivary irisin, and pain catastrophizing together within a biopsychosocial pain framework.
This is a prospective, randomized, controlled clinical trial. Adults with asymptomatic apical periodontitis in single-rooted, single-canal mandibular premolar teeth will receive single-visit root canal treatment from a single operator and will be randomly assigned to one of two groups. The intervention group will receive final irrigation with cooled saline, and the control group will receive final irrigation with room-temperature saline, using the same irrigation device. A group of healthy individuals will provide a single saliva sample for reference values.
Postoperative pain will be assessed with the Visual Analog Scale. Pain catastrophizing and dental anxiety will be assessed with validated questionnaires before treatment. Saliva samples will be collected before and after treatment to measure irisin levels.
The findings may clarify whether cryotherapy is associated with reduced postoperative pain and a change in a salivary inflammatory biomarker, whether pain catastrophizing influences the effect of cryotherapy on postoperative pain, and whether salivary irisin can serve as a non-invasive biomarker in endodontics.
- Being tested
- Intracanal Cryotherapy, Standard Room-Temperature Irrigation
- Keywords
- Root canal treatment, Intracanal cryotherapy, Postoperative pain, Pain catastrophizing, Dental anxiety, Salivary irisin, Endodontics, Single-visit root canal treatment
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intracanal CryotherapyProcedure or surgery
Following completion of the standard EndoVac irrigation protocol, a group-specific final irrigation step will be performed. Sterile saline solution, refrigerated at +2°C and further cooled to 2.5°C in an ice-water bath, with temperature verified using a digital thermometer, will be delivered using the EndoVac system. A total of 20 mL of cooled saline will be applied over 5 minutes, with the micro-cannula positioned at working length to ensure effective delivery of the cold irrigant to the apical region via negative pressure.
Standard Room-Temperature IrrigationProcedure or surgery
Following completion of the standard EndoVac irrigation protocol, a group-specific final irrigation step will be performed. Sterile saline solution prepared at room temperature (20-22°C) will be delivered using the EndoVac system, following the same protocol as the intervention group. A total of 20 mL of room-temperature saline will be applied over 5 minutes, using the same technique and duration.
| Study group | Role | What they receive |
|---|---|---|
| Intracanal Cryotherapy | Experimental | Participants undergoing single-visit root canal treatment will receive intracanal cryotherapy using a cold irrigant delivered through a closed-system irrigation device (EndoVac) after completion of canal instrumentation and prior to obturation. Receives: Procedure: Intracanal Cryotherapy |
| Control (Room-Temperature Irrigation) | Active comparator | Participants undergoing single-visit root canal treatment will receive standard irrigation using the same closed-system irrigation device (EndoVac) with irrigant at room temperature, following the same canal instrumentation protocol as the intervention group. Receives: Procedure: Standard Room-Temperature Irrigation |
| Healthy Reference Group | No intervention | Saliva samples will be collected from healthy participants without an indication for root canal treatment, solely for the purpose of establishing normative salivary irisin reference values. These participants will not be randomized, will not undergo root canal treatment, and will not receive any study intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative Pain as Assessed by Visual Analog Scale (VAS)
Postoperative pain will be self-assessed by participants using a 100 mm Visual Analog Scale (VAS), consisting of a horizontal line where participants mark the point that best represents their level of pain intensity. The left end (0 mm) indicates "no pain" and the right end (100 mm) indicates "the most severe pain I have ever felt in my life." Scores are measured in millimeters, with higher scores indicating greater pain intensity. Participants will record their VAS score in a standardized pain diary at each assessment time point, along with any rescue analgesic (paracetamol 500 mg) use, including time and dose, and any adverse events or unexpected occurrences. A blinded researcher, unaware of group allocation, will telephone participants at each designated time point to record pain scores and remind them to complete the diary.
Measured: 24 hours after root canal treatment
Secondary outcomes (11)
Postoperative Pain as Assessed by Visual Analog Scale (VAS) at 6 Hours
Postoperative pain will be self-assessed using a 100 mm Visual Analog Scale (VAS). The left end (0 mm) indicates "no pain" and the right end (100 mm) indicates "the most severe pain I have ever felt in my life." Higher scores indicate greater pain intensity.
Measured: 6 hours after root canal treatment
Postoperative Pain as Assessed by Visual Analog Scale (VAS) at 12 Hours
Postoperative pain will be self-assessed using a 100 mm Visual Analog Scale (VAS). The left end (0 mm) indicates "no pain" and the right end (100 mm) indicates "the most severe pain I have ever felt in my life." Higher scores indicate greater pain intensity.
Measured: 12 hours after root canal treatment
Postoperative Pain as Assessed by Visual Analog Scale (VAS) at 48 Hours
Postoperative pain will be self-assessed using a 100 mm Visual Analog Scale (VAS). The left end (0 mm) indicates "no pain" and the right end (100 mm) indicates "the most severe pain I have ever felt in my life." Higher scores indicate greater pain intensity.
Measured: 48 hours after root canal treatment
Postoperative Pain as Assessed by Visual Analog Scale (VAS) at 72 Hours
Postoperative pain will be self-assessed using a 100 mm Visual Analog Scale (VAS). The left end (0 mm) indicates "no pain" and the right end (100 mm) indicates "the most severe pain I have ever felt in my life." Higher scores indicate greater pain intensity.
Measured: 72 hours after root canal treatment
Postoperative Pain as Assessed by Visual Analog Scale (VAS) at 7 Days
Postoperative pain will be self-assessed using a 100 mm Visual Analog Scale (VAS). The left end (0 mm) indicates "no pain" and the right end (100 mm) indicates "the most severe pain I have ever felt in my life." Higher scores indicate greater pain intensity.
Measured: 7 days (168 hours) after root canal treatment
Pain Catastrophizing as Assessed by Pain Catastrophizing Scale (PCS)
Pain catastrophizing will be assessed using the Pain Catastrophizing Scale (PCS), a validated self-report questionnaire measuring the tendency to exaggerate the threat value of pain. Higher scores indicate greater pain catastrophizing.
Measured: Baseline, prior to root canal treatment
Dental Anxiety as Assessed by Modified Dental Anxiety Scale (MDAS)
Dental anxiety will be assessed using the Modified Dental Anxiety Scale (MDAS), a validated self-report questionnaire measuring anxiety related to dental treatment. Higher scores indicate greater dental anxiety.
Measured: Baseline, prior to root canal treatment
Salivary Irisin Level at Baseline
Salivary irisin concentration will be measured in unstimulated saliva samples collected using the passive drooling method, analyzed by enzyme-linked immunosorbent assay (ELISA).
Measured: Baseline, prior to root canal treatment
Salivary Irisin Level at 24 Hours
Salivary irisin concentration will be measured in unstimulated saliva samples collected using the passive drooling method, analyzed by enzyme-linked immunosorbent assay (ELISA).
Measured: 24 hours after root canal treatment
Salivary Irisin Level at 72 Hours
Salivary irisin concentration will be measured in unstimulated saliva samples collected using the passive drooling method, analyzed by enzyme-linked immunosorbent assay (ELISA).
Measured: 72 hours after root canal treatment
Salivary Irisin Level in Healthy Reference Group
Salivary irisin concentration will be measured in a single unstimulated saliva sample collected from healthy participants without an indication for root canal treatment, using the passive drooling method and analyzed by enzyme-linked immunosorbent assay (ELISA), to establish normative reference values.
Measured: At the time of saliva sample collection, single time point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2026
- Study start1 Nov 2026 (estimated)
- Primary completion15 Nov 2027 (estimated)
- Study completion15 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Postoperative Pain After Endodontic TreatmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In this study, participants undergoing root canal treatment will be randomized to one of two intervention groups: intracanal cryotherapy or control. Participants in these two groups will be masked to group allocation, as local anesthesia is administered prior to root canal treatment, preventing them from perceiving the temperature of the irrigant used. The treating clinician (care provider) cannot be masked, as the irrigant is administered directly by this individual. Outcomes assessors, who record and evaluate postoperative pain, pain catastrophizing, dental anxiety, and salivary irisin data, will be masked to group allocation and will not know which group each participant belongs to. An additional healthy reference group (n=30) is included solely to establish normative salivary irisin values and does not receive any study intervention. This group is not randomized, and the concept of masking does not apply, as participants in this group only provide a saliva sample.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alanya Alaaddin Keykubat University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hatice BÜYÜKÖZER ÖZKAN, Alanya Alaaddin Keykubat University
- Investigators
- Hatice Buyukozer Ozkan, PhD, Principal investigator, Alanya Alaaddin Keykubat University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07889050
- Sponsor's protocol ID
- ALKU-EC-2026-58
- Acronym
- CRYO-IRIS
- Status last verified
- Oct 2026
- First submitted
- 16 Oct 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share individual participant data, as no data-sharing repository or mechanism has been established for this study. Only aggregate results will be published.
Publications
Salim FS, Saliem SS. Irisin, a promising adipomyokine, shows low levels in relation to periodontal diseases, unlike visfatin and IL-6 (case-control study). Front Oral Health. 2025 Nov 6;6:1614433. doi: 10.3389/froh.2025.1614433. eCollection 2025.
PubMed 41280712Gastmann AH, Xavier SR, Pilownic KJ, Romano AR, Gomes FA, Goettems ML, Morgental RD, Pappen FG. Pain, anxiety, and catastrophizing among pregnant women with dental pain, undergoing root canal treatment. Braz Oral Res. 2024 Jun 24;38:e054. doi: 10.1590/1807-3107bor-2024.vol38.0054. eCollection 2024.
PubMed 38922214Rahman MM, Hwang SM, Go EJ, Kim YH, Park CK. Irisin alleviates CFA-induced inflammatory pain by modulating macrophage polarization and spinal glial cell activation. Biomed Pharmacother. 2024 Sep;178:117157. doi: 10.1016/j.biopha.2024.117157. Epub 2024 Jul 22.
PubMed 39042964Almohaimede A, Al-Madi E. Is Intracanal Cryotherapy Effective in Reducing Postoperative Endodontic Pain? An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials. Int J Environ Res Public Health. 2021 Nov 9;18(22):11750. doi: 10.3390/ijerph182211750.
PubMed 34831517