Effect of intracanal cryotherapy on the inflammatory cytokine, proteolytic enzyme levels and post-operative pain in teeth with asymptomatic apical periodontitis: A randomized clinical trial

Keskin C., Aksoy A., Kalyoncuoğlu E., Keleş A., İlik A. A., Kömeç O., ...More

International Endodontic Journal, vol.56, no.8, pp.932-942, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 56 Issue: 8
  • Publication Date: 2023
  • Doi Number: 10.1111/iej.13937
  • Journal Name: International Endodontic Journal
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, EMBASE, MEDLINE
  • Page Numbers: pp.932-942
  • Keywords: cryotherapy, endodontic pain, interleukin, matrix metalloproteinase, prostaglandin
  • Istanbul Medipol University Affiliated: Yes


Aim: To investigate the changes in the biomarker levels related to inflammation and tissue destruction in the periapical exudate of mandibular pre-molar teeth with asymptomatic apical periodontitis after receiving intracanal cryotherapy, to compare cryotherapy and control groups in terms of analgesic intake, interappointment, and post-operative pain and evaluate the correlation between biomarker levels and interappointment pain. Methodology: Mandibular pre-molar teeth of 44 patients aged 18–35 years, diagnosed with asymptomatic apical periodontitis, were root canal treated in two visits (registered as NCT04798144). Baseline periapical exudate samples were obtained, and the patients were assigned to either control or intracanal cryotherapy group according to the final irrigation with distilled water either at room temperature or 2.5°C. The canals were dressed with calcium hydroxide. In the second visit, the calcium hydroxide was removed with passive ultrasonic irrigation, and the periapical exudate was sampled again. IL-1β, IL-2, IL-6, IL-8, TNF-α, PGE2 and MMP-8 levels were determined with ELISA. Post-operative pain levels were recorded for 6 days following both visits using a visual analogue scale. Data were analysed using t-test, the Mann–Whitney U test and correlation tests. Results: There was a significant correlation between the pain scores reported after first visit and IL-1β and PGE2 levels (p <.05). IL-1β, IL-2 and IL-6 levels showed no significant difference in the cryotherapy group (p >.05), while they significantly increased in the control group (p <.05). There was a decrease in IL-8, TNF-α, PGE2 and MMP-8 levels, however, the difference was not significant (p >.05). Pain scores were significantly lower in the cryotherapy group for the first 3 days (p <.05), except for 24th hours (p >.05). Conclusions: The positive correlation between interappointment pain and IL-1β and PGE2 levels might indicate that these biomarker levels can be used to predict the severity of post-operative pain. Intracanal cryotherapy was effective in reducing post-operative pain in the short term in teeth with asymptomatic apical periodontitis. Cryotherapy prevented an increase in IL-1β, IL-2 and IL-6 levels compared with the control group.