Introduction

Endodontics is the branch of dentistry that studies dental pulp diseases and those affecting teeth with necrotic pulp, whether with or without periapical complications ¹. It encompasses the etiology, diagnosis, prevention, and treatment of dental pulp diseases and their complications ². Most often, these conditions are pulpal or periapical inflammatory states, with dental caries being the predominant etiological factor ⁽³.

The term cryotherapy derives from the Greek cryos meaning cold, and therapeia, indicating cure ⁴; that is, lowering tissue temperature for therapeutic purposes, not by implementing cold but rather by extracting heat ⁵. Local cooling of a body area is achieved by transferring body heat to an external element whose temperature is much lower. Heat exchange occurs through various physical mechanisms: conduction, convection, and evaporation ⁶.

A common fear among patients undergoing endodontic treatment is the possibility of experiencing pain. Pain is defined as "an unpleasant sensory and emotional experience associated with or similar to that associated with actual or potential tissue injury" ⁷.

In recent times, cryotherapy has gained popularity as a technique to alleviate postoperative pain. When utilized in surgery, it is referred to as cryosurgery. In dentistry, cryotherapy is employed following extractions, periodontal and implant surgeries to mitigate pain ⁸. Cryoanesthesia, a form of topical anesthesia, is utilized to alleviate pain in the skin and mucous membranes through cooling without inducing freezing. It can be employed in some dental procedures ⁹.

Pain following endodontic treatment can be highly frustrating for both the patient and the dentist. Typically, patients assess pain and post-appointment swelling as indicators of the practitioner's expertise. Such patient experiences and misconceptions underscore the significance of minimizing postoperative endodontic pain ¹⁰.

Objectives

General: To elucidate the utilization of cryotherapy in endodontics.

Specific:

Methodology

This work is a narrative review. A comprehensive literature search was conducted using the following MeSH (Medical Subject Heading) terms: cryotherapy, endodontic, intracanal irrigation, dental pain, along with their corresponding descriptors in DeCS health sciences: crioterapia, endodoncia, irrigación intracanal, and dolor dental.

The search was enhanced by a manual examination of references cited in the selected articles. Both primary and secondary sources of information were consulted. The search period extended from May 2021 to May 2023. An electronic bibliographic review of the literature was conducted across the Bireme (bvs) and PubMed databases, combining keywords such as Endodontic, Cryotherapy, Intracanal irrigation, Dental pain, and their equivalents in Spanish and Portuguese.

Background

In 3000 BC, the Egyptians were the first to apply cryotherapy to reduce inflammation and treat injuries. In ancient Greece, Hippocrates recommended the local or systemic application of cold for therapeutic purposes on injured individuals in 400 BC ^10,11. However, it was James Arnott in 1851 who first reported and demonstrated the use of freezing therapy to treat a malignant disease using a mixture of salt and ice ⁽⁴.

Cryotherapy has been utilized for many years in managing pain and facilitating postoperative recovery in sports injuries and surgical procedures. It has demonstrated effectiveness in reducing edema, pain, swelling, and recovery time with short-term applications in orthopedic, abdominal, gynecological, and hernia surgeries ¹². Cryotherapy is defined as the therapeutic application of any substance to the body that removes heat, resulting in a decrease in tissue temperature ¹³.

In dentistry, it is commonly employed after intraoral surgical procedures to control postoperative pain ¹². It is effective in treating various soft tissue lesions of the oral cavity, including keratotic, hyperplastic, granulomatous, vascular, pigmented, and salivary gland lesions. It has a significant advantage over other treatment modalities: it leaves minimal or no scarring. It is highly beneficial for treating mucous cysts of the floor of the mouth due to their minimal tendency to recur ¹⁴.

Development

Symptomatic apical periodontitis is the typical manifestation of postendodontic pain. It entails an acute inflammatory reaction akin to that observed in other connective tissues of the body, characterized by vasodilation, increased vascular permeability, and leukocyte migration from blood vessels to the site of tissue injury. Inflammatory mediators regulate this process, resulting in tissue damage, pain, and swelling. Cryotherapy has three fundamental effects: on vascular, neurological, and tissue metabolism ¹⁴.

At the vascular level, it induces vasoconstriction and slows down metabolism by decreasing biochemical reactions, thereby limiting oxygen demand at the cellular level and reducing the formation of free radicals in the tissues ⁽¹⁵. Consequently, the amount of fluid leakage at the periradicular level as exudate decreases, resulting in reduced edema and swelling following biomechanical preparation ⁴. The most significant vasoconstriction occurs at a temperature of 15°C ⁽¹⁵. At the neurological level, the application of cold induces analgesia in nociceptive nerve fibers by reducing conduction velocity. This effect differs between myelinated A-δ (A delta) nerve fibers and unmyelinated C nerve fibers; the former are completely deactivated at 7°C, while the latter are deactivated at 3°C. Additionally, it stimulates the secretion of endorphins, which bind to receptors in the dorsal horn of the spinal cord, inhibiting nociceptive transmission to the central nervous system. Another consequence of cryotherapy is the inhibition of tissue nociceptors, resulting in a local anesthetic effect known as cold neuropraxia ¹⁶. At the level of tissue metabolism, there is a decrease in the speed of biochemical reactions, leading to reduced formation of free radicals in the tissues, lower oxygen consumption, prevention of hypoxia and other cellular lesions ⁽⁴.

In the oral and dental field, nociceptive stimuli on the pulp and/or periodontal tissue lead to the release of chemical mediators from two sources: bradykinin from plasma and prostaglandin E2 (PGE2) from damaged cells. Both act on trigeminal free nerve endings, with PGE2 sensitizing them and bradykinin completing the excitation, resulting in action potentials in afferent nerve fibers that convey pain to the central nervous system (CNS) ⁽¹⁷.

Pain control in endodontic therapy requires good management in daily practice, given its potential to cause patient dissatisfaction and impact their quality of life. The incidence of pain in endodontic treatment ranges from 3 to 58%, and at the end, it may be due to mechanical and chemical lesions, along with the presence of microorganisms in the periapical region ¹⁸. Several strategies for pain and inflammation control include occlusal reduction, long-term anesthesia administration ¹⁹, psychological treatment ²⁰, and the use of various mechanical techniques during canal procedures ⁸. Moreover, the use of non-steroidal anti-inflammatory drugs such as paracetamol or corticosteroids, though the second option poses side effects such as renal and hepatic disorders, gastrointestinal intolerance, and even asthma. In order to avoid these inconveniences, alternative treatments such as lymphatic drainage, laser, cryotherapy ⁽¹⁶ and phototherapy ⁽²¹ are suggested.

Vera et al., 2015 introduced cryotherapy in endodontics. In an ex vivo study on 20 freshly extracted human uniradicular teeth, they observed a significant reduction in the external temperature of the apical 4 mm of the root by 10°C. This reduction persisted for at least 4 minutes after continuous irrigation with 20 ml of cold saline at 2.5°C for 5 minutes using the Endo Vac (Endodontic Vacuum) system ⁵. It is a negative pressure irrigation procedure that involves an irrigation/evacuation tip connected to a syringe containing the irrigant and to the suction system of the dental unit, along with a small device where the microcannula and macrocannula are placed. The microcannula can be utilized at the working length in canals instrumented to a minimum caliber of #35 within a specific timeframe ²². Since then, numerous clinical and in vitro studies have been conducted on the application of intracanal cryotherapy (see Table 1), primarily focusing on the reduction of postendodontic pain, with a consistent decrease reported by various authors.

There is no consensus on the duration required for a therapeutic effect of cryotherapy. However, physiotherapy studies by Grant showed that treating 7000 ambulatory patients with ice therapy for between 5 and 7 minutes is adequate to induce muscle numbness. Waylonis reported evidence of superficial anesthesia after massaging the legs with ice for 4.5 minutes. Mc Gown demonstrated changes in inflamed quadriceps muscle tissue following a 5-minute ice massage ⁵. At the dental level, there are differences in the transmission of cold to the periodontal ligament in the apical and coronal portions of the tooth due to differences in dentin width and mineralization in these areas. The root of the cervical third contains more dentinal tubules with larger diameters, while the apical third is denser and more mineralized. Apical sclerotic dentin is less permeable than coronal dentin ⁵. Uniradicular teeth in the apical third typically present 1 to 7 pulp ramifications, which enhance cold transmission compared to multirooted teeth ²³. Another question pertains to the temperature at which cellular death occurs, which seemingly does not occur at temperatures above -20°C, although most tissues freeze at -2.2°C ⁽⁵. The reduction in blood flow and cellular metabolism induced by cryotherapy triggers an anti-edema effect, thereby contributing to analgesia ²⁴.

Table 1: Published Research on Cryotherapy in Endodontics

Note: N/D indicates not described.

Discussion:

Endodontic treatment provides a favorable environment in the periradicular region for healing by thoroughly removing tissue debris and minimizing the presence of microorganisms in the root canal system, followed by complete obturation in all three dimensions (3D) of the shaped root canal space ^37,39. However, the treatment process itself can induce pain. Various strategies, including cryotherapy, the latest advancement in endodontics, are suggested to mitigate this issue ³⁷. Cryotherapies involving ice, cold water, and cold air have gained popularity due to their ability to remove heat, lower tissue temperature, and modify blood flow in humans ⁴⁴. Postoperative pain is one of the major problems in endodontic treatment, even when proper treatment steps are followed ⁴⁵. Teeth with periapical pathology are at greater risk of developing pain, and symptomatic teeth are more likely to have pain regardless of the condition of the dental pulp ²⁹. Postoperative pain is the result of a complex multifactorial process influenced by factors inherent to the patient, the tooth undergoing treatment, the intervening operator ¹⁶, as well as inflammatory chemical mediators, cyclic nucleotide changes, modifications in local adaptation, and periapical tissue pressure ³⁶. Periradicular inflammation arises from mechanical, microbial, and/or chemical injury to the periapical tissues. Even when not forced through the apical foramen, filling materials provoke an inflammatory reaction ¹². Cold saline solutions used as final irrigations have been proven to reduce the external root surface temperature by over 10°C, maintaining it for 4 minutes ⁵. This decrease in external root surface temperature limits inflammatory reactions, the production and release of algesic substances, and the edema in the periapical region. Cryotherapy slows down peripheral nerve conduction, gradually reducing the speed of nerve fiber conduction until it halts completely. Concerning dental pulp, complete deactivation of A-δ fibers and partial deactivation of C fibers occur around 3°C ³⁷. Ernst and Fialka observed that moderate cold application could not diminish nerve conduction in C fibers. It also activates thermal receptors that reduce the transmission of painful stimuli ⁽¹². Among the advantages of cryotherapy, its ease of application stands out, as it does not require any additional attachments - while it can be applied more effectively with the Endo Vac system, it is not a necessary requirement. This was demonstrated by Sadaf et al. in their meta-analysis comparing the use of Endo Vac to a syringe with a needle, where they concluded that there are no significant differences in using these instruments for cryotherapy application ⁴⁶. Endovac is linked to a lower risk of extrusion of the irrigation agent and apical detritus into periapical tissues and maxillary sinuses ²⁴.

Sodium hypochlorite (NaOCl) is the most widely employed irrigant in endodontics due to its extensive antimicrobial activity and ability to dissolve organic matter. However, it is irritating to periapical tissues, particularly at high concentrations. The concentration of NaOCl varied among studies; in Yadav's research, it was substituted with Herbal Triphala to prevent potential irritation, along with EDTA ³². The absence of a standardized cryotherapy protocol results in a lack of uniformity regarding the type, volume, and temperature of the irrigation agent used. Among the studies presented, saline was the most commonly utilized irrigation solution for cryotherapy, followed by EDTA combined with saline. The volume and temperature varied, ranging from 5 to 20 ml and from 1°C to 15°C.

While the protocols employed in the studies vary significantly, the majority of them reported lower rates of postoperative pain in cryotherapy groups compared to control groups, regardless of the agent, volume, or temperature used. Therefore, the type of irrigant agent may be considered less important than maintaining low temperatures, which promote local analgesia and reduce the likelihood of postoperative pain ⁽⁴⁷. Both Gundogdu ¹⁰ and Yadav ⁽³¹⁾ conducted studies utilizing intraoral and extraoral cryotherapy in the same way. The only difference was in the wrapping material used for the piece of ice in the extraoral application; Gundogdu used paper instead of gauze. In both cases, a significant reduction in postoperative pain was observed compared to the control group, as well as with intracanal application. Thus, despite being more uncomfortable for the patient, it could be considered as an alternative application method to take into account ³¹. One of the primary problems regarding intracanal cryotherapy, as indicated by the in vitro studies conducted by Keskin ³¹ and Jain ³⁸, is the reduction in tooth fracture resistance. Despite both studies utilizing the same volume, duration, and irrigation temperature of 2.5°C, Western's investigation deviated from the commonly used temperature range of 2 to 4°C to a higher range of 13 to 15°C and still achieved a comparable reduction in pain. Therefore, further in vitro or clinical studies employing this temperature range are necessary to assess the long-term effects on tooth strength ⁽⁴².

Patients can assess their pain levels using a Visual Analog Scale (VAS) questionnaire, categorizing pain as follows: 0 for no pain; 1-3 for mild pain; 4-6 for moderate pain; 7-9 for severe pain; and 10 for the worst pain ²⁹. (Fig. 1)

Figure 1: Visual Analog Scale ²⁹  

In Jaiswall's study ³⁴, pain scores were low in the cryotherapy group, despite a reduced intake of analgesics, suggesting the potential simultaneous use of these two methods ⁽²⁴. A systematic review and meta-analysis conducted by Smith et al. regarding NSAIDs for post-endodontic pain management concluded that ibuprofen is an effective analgesic for controlling post-endodontic pain ²⁹. Furthermore, Di Spirito's study of systematic review recommends ibuprofen 600 mg alone or combined with paracetamol 1000 mg as the first-choice treatment ²¹. Studies by Vieyra, Alharthi, Akpinar, Jaiswall, and Western underscore that cryotherapy diminishes post-endodontic pain and the necessity for analgesic medication, with no statistically significant differences observed among the procedures employed ^{29,30, 34,40,42}. Cryotherapy alleviates pain associated with both symptomatic irreversible pulpitis and symptomatic apical periodontitis ⁽⁴⁸. In these cases, its effect may be greater as inflammation is not confined within the root canal. This can be explained by the cold saline solution's effect on reducing edema and inflammation, acting as an anti-inflammatory in the periapical area ²⁶. Emad's studies ⁴¹ elucidate the mechanism of action of cryotherapy concerning inflammatory markers known as cytokines. Comparative results of cryotherapy application against control groups reveal reduced levels of proinflammatory cytokines IL-1β and IL-6, alongside elevated levels of the anti-inflammatory cytokine IL-10. A recent study by Keskin also demonstrated a reduction in cytokines IL-1β, IL-6, and IL-2 ⁴³. Interleukins 1β, IL-6, and IL-10 have been widely studied for their role in the pathophysiology of periradicular disease. Moreover, they are considered the most important in human osteoclastic activity, with their presence correlating to the size of periapical lesions. Strict counteraction of proinflammatory pathways is essential to prevent unnecessary tissue damage. There is a balance between proinflammatory and anti-inflammatory cytokines in chronic inflammatory processes regulating the degree of host response to antigen stimulation ²³.

Conclusions:

Based on this narrative review, there is scientific evidence supporting the application of cryotherapy for pain management in endodontics, particularly in cases of symptomatic irreversible pulpitis and symptomatic apical periodontitis. Further clinical studies with diverse initial diagnoses are necessary, although cryotherapy is likely to yield similar effects in pain reduction. Moreover, it can be supplemented with other methods to achieve this objective.

As of now, there is no specific clinical protocol established regarding the ideal temperature of the irrigant, the most suitable one, and the application duration. Cryotherapy proves to be an easily applicable method with few contraindications, non-toxic, and requiring minimal economic investment from professionals. Additional clinical studies should be conducted to investigate the effect of cryotherapy on tooth fracture resistance, which poses a limitation in its application due to the less conclusive findings of in vitro studies.