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ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. AIM OF THE STUDY: To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. MATERIALS AND METHODS: The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. RESULTS: FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and ß-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. CONCLUSIONS: FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.

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BACKGROUND: One of the challenges of physical training in extreme condition is frostbite, especially in Northeast China. In this study, we aimed to construct a risk prediction model for frostbite among soldiers in Northeast China, and verify its effect. METHODS: 698 participants were selected via convenience sampling from Northeast China from December 2021 to January 2022 (winter). They were randomly divided into a training set (N = 479) and a testing set (N = 202) in a ratio of 7:3. All participants completed a researcher-made questionnaire on frostbite. The prediction model was constructed through the use of Logistic regression analysis, which was used to predict the independent risk factors for frostbite formation and screen significant indicators. The model's performance was assessed using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) to evaluate the prediction efficiency and goodness of fit. RESULTS: The incidence of frostbite in the training set was 19.83% (95 people), all of which were first-degree frostbite. Among them, frostbite in multiple parts was the most common (58.95%), followed by singular body parts like hands (24.21%), ears (11.58%) and feet (5.26%). Single factor logistic regression analyses showed that ambient temperature, ambient wind speed, outdoor stationary time, stationary status, and history of frostbite are independent risk factors that affect the occurrence of frostbite. Furthermore, we constructed the frostbite risk prediction model for soldiers in the northeastern region of China. The area under the receiver operating characteristic curve (AUC) for the risk of frostbite in the training set and testing set was 0.816 (95% CI, 0.770 ~ 0.862) and 0.787 (95% CI, 0.713 ~ 0.860), respectively. The Hosmer-Lemeshow test of the model showed χ2 = 11.328 and P = 0.184 (> 0.05). The DCA curve indicated that most of the clinical net benefits of the model are greater than 0, demonstrating good clinical usefulness. CONCLUSION: The constructed frostbite prediction model can effectively identify soldiers with a higher risk of frostbite. It provided theoretical support for commanders to take preventive measures to reduce the incidence of frostbite among soldiers and was of great clinical guiding significance.

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Dr William J. Mills Jr., an Alaskan orthopedic surgeon, helped establish the current protocols for frostbite treatment and changed a dogma used for more than 140 years that was established by Napoleon's surgeon general of the army, Baron Dominique-Jean Larrey. During Napoleon's 1812 siege of Moscow, Larrey noticed the destructive effects of using open fire heat for warming frozen body parts, so he suggested rubbing snow or immersion in cold water. Dr Mills treated many cold injuries during his medical career. After setting up his medical practice in Anchorage, Alaska, he realized the inefficiency of the established protocols and started researching new treatments for frostbite. Dr Mills followed Meryman's method of rapidly thawing frozen red blood cells in warm water. Mills and his colleagues established a treatment protocol for freezing cold injury that included rapid warming in warm water. These studies resulted in the publication of three key papers in 1960 and 1961. These papers were the first clinical studies that described rapid warming as a treatment. Subsequently, rapid warming, with some variation in water temperatures, has been accepted as the standard of treatment. Due to his outstanding contribution to the treatment of frostbite, he has been referred to as "the nation's leading authority on cold injury." Mills and his colleagues created a new classification system that divided frostbite into two levels, superficial and deep, which was more applicable in clinics than the traditional 4-tier classification. The 2-tier classification is still useful outside of the hospital setting.

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Frostbite, a severe cold injury resulting from exposure to subfreezing temperatures, damages the skin and underlying tissues of the affected area and ranges in severity from first to fourth degree. This case report investigates the impact of second-degree frostbite suffered by a marine during winter training on cold-induced vasodilation (CIVD). Comparisons of CIVD before and after the injury revealed significant alterations in CIVD responses. CIVD, a physiological mechanism characterized by blood vessel dilation in response to cold exposure, plays a crucial role in operating in cold-weather environments and enhancing dexterity. The marine exhibited prolonged CIVD onset time, lower finger temperatures, increased pain sensations, and diminished dexterity after the frostbite injury during follow-up CIVD testing. The findings suggest that the frostbite-induced damage possibly compromised the microvascular function, contributing to the observed changes in CIVD. The marine reported persistent cold sensitivity and difficulty in maintaining hand warmth when assessed postinjury. This case underscores the potential long-term consequences of frostbite on CIVD and manual dexterity, emphasizing the importance of understanding these physiological changes for individuals engaged in cold-weather activities, particularly for military and occupational personnel.

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BACKGROUND: Hyperbaric oxygen (HBO2) treatment is used across a range of medical specialties for a variety of applications, particularly where hypoxia and inflammation are important contributors. Because of its hypoxia-relieving and anti-inflammatory effects HBO2 may be useful for new indications not currently approved by the Undersea and Hyperbaric Medical Society. Identifying these new applications for HBO2 is difficult because individual centers may only treat a few cases and not track the outcomes consistently. The web-based International Multicenter Registry for Hyperbaric Oxygen Therapy captures prospective outcome data for patients treated with HBO2 therapy. These data can then be used to identify new potential applications for HBO2, which has relevance for a range of medical specialties. OBJECTIVE: Although hyperbaric medicine has established indications, new ones continue to emerge. One objective of this registry study was to identify cases where HBO2 has been used for conditions falling outside of current Undersea and Hyperbaric Medical Society-approved indications and present outcome data for them. METHODS: This descriptive study used data from a web-based, multicenter, international registry of patients treated with HBO2. Participating centers agree to collect data on all patients treated using standard outcome measures, and individual centers send deidentified data to the central registry. HBO2 treatment programs in the United States, the United Kingdom, and Australia participate. Demographic, outcome, complication, and treatment data, including pre- and posttreatment quality of life questionnaires (EQ-5D-5L) were collected for individuals referred for HBO2 treatment. RESULTS: Out of 9726 patient entries, 378 (3.89%) individuals were treated for 45 emerging indications. Post-COVID-19 condition (PCC; also known as postacute sequelae of COVID-19; 149/378, 39.4%), ulcerative colitis (47/378, 12.4%), and Crohn disease (40/378, 10.6%) accounted for 62.4% (n=236) of the total cases. Calciphylaxis (20/378, 5.3%), frostbite (18/378, 4.8%), and peripheral vascular disease-related wounds (12/378, 3.2%) accounted for a further 13.2% (n=50). Patients with PCC reported significant improvement on the Neurobehavioral Symptom Inventory (NSI score: pretreatment=30.6; posttreatment=14.4; P<.001). Patients with Crohn disease reported significantly improved quality of life (EQ-5D score: pretreatment=53.8; posttreatment=68.8), and 5 (13%) reported closing a fistula. Patients with ulcerative colitis and complete pre- and post-HBO2 data reported improved quality of life and lower scores on a bowel questionnaire examining frequency, blood, pain, and urgency. A subset of patients with calciphylaxis and arterial ulcers also reported improvement. CONCLUSIONS: HBO2 is being used for a wide range of possible applications across various medical specialties for its hypoxia-relieving and anti-inflammatory effects. Results show statistically significant improvements in patient-reported outcomes for inflammatory bowel disease and PCC. HBO2 is also being used for frostbite, pyoderma gangrenosum, pterygium, hypospadias repair, and facial filler procedures. Other indications show evidence for improvement, and the case series for all indications is growing in the registry. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/18857.

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This study examines a rare case of frostbite on the hands caused by liquid nitrogen, focusing on the scar maturation process. Frostbite is typically less prone to abnormal scarring compared to burns, and this report contrasts the differences in scar maturation between the two. A 31-year-old male hospital employee sustained first- to second-degree frostbite on his gloved hands from a 20-s exposure to liquid nitrogen while changing a cylinder. Conservative treatment was applied, and the patient was monitored for 9 months. The deeply affected area took 50 days to epithelialize but healed without hypertrophic scarring. A mild extension contracture was noted in the distal interphalangeal joint of the right index finger, but the skin remained supple and soft. Incidents of liquid nitrogen-induced frostbite are uncommon, with only 14 cases reported in PubMed previously. In frostbite, the wound healing involves a slow replacement of damaged connective tissue, which acts as an internal splint, reducing wound contraction. This contrasts with burns, where rapid connective tissue replacement occurs, often leading to significant wound contraction due to the presence of myofibroblasts in granulation tissue. In the presented case, the slow healing process and minimal wound contraction led to mature scarring without abnormalities, underlining a distinctive healing trajectory in frostbite injuries compared to burns.

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Cold injury has been documented for centuries and remains a concern for military personnel, winter recreationalists, and urban homeless populations. Treatment advances in the last decades have included thrombolytic and prostaglandin therapies however the mainstay remains early recognition and rapid rewarming. This chapter focuses on frostbite, with a brief overview of other cold related conditions.

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Fossati, Alexandre, and Aleid C. J. Ruijs. Changes in fingertip cold-induced vasodilatation (hunting reaction) on acute exposure to altitude. High Alt Med Biol. 25:212-217, 2024. Objective: Cold-induced vasodilation (CIVD) of the extremities is an interesting part of human physiology. Although the physiology of the CIVD reaction remains unknown, there are indications that hypoxia influences our CIVD reaction. The objective of this study is to measure the influence of acute hypoxia on the CIVD reaction of the fingertips. Methods: The CIVD reaction was measured using immersion of one hand in a water bath of 0°C in 12 healthy volunteers at low (1,235 m) and high (3,800 m) altitude during 35 minutes. High altitude was reached by a 20-minute cable car ride. Testing was performed indoors (room temperature, 22-25°C) at both altitudes. Data analysis was performed measuring the parameters of the CIVD reaction. Differences were found using the paired Student's t-test. Results: There was no significant difference in baseline finger temperature, onset time, peak time, and frequency of the CIVD reaction. However, at high altitude, maximum temperature and amplitude were significantly higher, slope was steeper, and minimum temperature was lower. Conclusion: We did not find evidence for a diminished CIVD reaction at high altitude due to hypoxia.

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This case report describes a unique scenario in which antimycobacterial-induced peripheral neuropathy (PN) culminates in severe bilateral foot frostbite. Drug-induced peripheral neuropathy (DIPN) is explored in the context of TB treatment, highlighting the role of medications such as isoniazid (INH) and their potential to cause PN. The report highlights the importance of identifying PN in patients undergoing antimycobacterial treatment. Early recognition and proper management of PN is crucial to prevent complications. Notably, the report advocates for patient education regarding medication side effects and avoiding harmful practices, such as ice immersion, to alliviate neuropathic pain. Emphasis is directed towards the need for a multidisciplinary approach to patient care and a focus on preventative strategies to improve patient outcomes and avoid severe debilitating complications.

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Background: Frostbite is a chemia resulting from cold-induced skin damage. The process of frostbite is often accompanied by inflammation, and the therapeutic strategies focusing on anti-inflammation are the main direction to data. Tat-CIRP is a 15 amino acid peptide containing HIV protein and cold-inducible RNA-binding protein (CIRP), which is believed to compete with endogenous CIRP for myeloid differentiation 2 (MD2) binding. This study aims to investigate the efficacy of Tat-CIRP in the treatment of frostbite. Methods: A mouse model of frostbite was established, and on the first day after frostbite occurrence, Tat-CIRP peptide was administered intravenously via the tail with a dosage interval of one day for a total of three doses. Frozen mouse skin sections were subjected to histological analysis, including hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemical examination. Western blotting was performed to detect the expression level of Ki-67 in mouse skin tissue. Results: One day after frostbite, mice exhibited skin swelling and a solid appearance. From day 1 to 5 after frostbite, MD2 expression was significantly upregulated, while CIRP expression was downregulated. Compared to the frostbite group, mice treated with Tat-CIRP showed accelerated frostbite recovery, reduced levels of inflammatory factors and MD2. Furthermore, the expression of cell proliferation-associated protein Ki-67 and angiogenesis-related protein CD31 was upregulated. Conclusion: Tat-CIRP promotes frozen wound healing via inhibiting inflammation and promoting angiogenesis in frostbitten mice.

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OBJECTIVE: Accurate assessment of burn depth and burn wound healing potential is essential to determine early treatments. Infrared thermography (IRT) is a non-invasive and objective tool to do this. This systematic review evaluated the accuracy of IRT to determine burn wound healing potential. METHOD: This systematic review and meta-analysis used MEDLINE, EMBASE, CINAHL, PEDro, DiTA and CENTRAL databases. IRT data were extracted from primary studies and categorised into four cells (i.e., true positives, false positives, true negatives and false negatives). Subgroup analysis was performed according to methods used to capture thermal images. RESULTS: The search strategy identified 2727 publications; however, 15 articles were selected for review and 11 for meta-analysis. In our meta-analysis, the accuracy of IRT was 84.8% (63% sensitivity and 81.9% specificity). CONCLUSION: IRT is a moderately accurate tool to identify burn depth and healing potential. Thus, IRT should be used carefully for evaluating burn wounds.

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This article examines the care provided for the welfare of soldiers by the three combatant countries - China, Korea and Japan - during the East Asian War of 1592-8. Also known as the Imjin War, this large-scale military conflict can also be understood as an encounter between different state cultures and strategies of military medicine. This study focuses on cold-induced injuries, epidemic outbreaks and external wounds suffered during the war. I illuminate provision of prophylactic measures against cold by the Ming state, as well as attempts by the Sino-Choson medical alliance to manage epidemics and treat wounded soldiers. I contrast these measures with the lack of similar centralised support for the Japanese forces, and examine the effect these differences had upon on military outcomes during the war. The difference in the amount of time, efforts and resources that the three combatant states devoted to sick and injured soldiers has implications not only for our understanding of the war but also for illuminating the early modern history of military medicine in East Asia. By exploring East Asian military medicine during and after the Imjin War, this article responds to recent calls for more detailed examination of histories of military medicine in premodern periods and non-European regions.

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The Wilderness Medical Society convened an expert panel to develop a set of evidence-based guidelines for the prevention and treatment of frostbite. We present a review of pertinent pathophysiology. We then discuss primary and secondary prevention measures and therapeutic management. Recommendations are made regarding each treatment and its role in management. These recommendations are graded on the basis of the quality of supporting evidence and balance between the benefits and risks or burdens for each modality according to methodology stipulated by the American College of Chest Physicians. This is an updated version of the guidelines published in 2019.

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BACKGROUND: Frostbite is a severe injury characterized by tissue damage due to exposure to freezing temperatures. It often necessitates prompt medical intervention to prevent further complications such as necrosis and amputation. This case report explores the successful use of bilateral anterolateral thigh (ALT) free flaps for feet salvage in a 19-year-old male refugee from Gambia who suffered severe frostbite injuries. CASE REPORT: The patient, found after six days in freezing conditions, exhibited necrosis on multiple toes. Initial management included stabilization, intravenous fluids, and rewarming. Subsequent necrectomy and amputation revealed exposed metatarsal bones, necessitating a meticulous reconstructive strategy. Bilateral ALT flaps were chosen to preserve walking function, with a staged reconstruction involving multiple operations. The patient's progress, from inpatient care to outpatient follow-ups, is detailed, emphasizing the challenges and decisions in managing severe frostbite injuries. RESULTS: The surgical intervention utilizing bilateral ALT flaps successfully salvaged the patient's feet. Throughout the postoperative period, wound care, rehabilitation, and outpatient monitoring contributed to positive outcomes. Despite challenges associated with the patient's ethnic background and nutritional status, the staged reconstruction facilitated effective healing and functional recovery. The use of ALT flaps provided a reliable solution with minimal donor site morbidity. CONCLUSION: This case highlights the efficacy of bilateral ALT flap reconstruction in salvaging feet following severe frostbite injury. The successful restoration of foot function underscores the importance of early intervention and tailored reconstructive approaches in frostbite management. Despite patient-specific challenges, including nutritional status and limited healthcare resources, the use of ALT flaps facilitated optimal recovery and functional outcomes. Importantly, this report is unique as it describes a novel case of feet salvage using bilateral ALT flaps in severe frostbite injury, with only one similar case previously reported in the literature. This emphasizes the rarity and significance of this specific surgical approach in frostbite management.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease that may be treated utilizing thermal therapies. Cryoablation is an effective, minimally invasive therapy that has been utilized for the treatment of various cancers, offering patients a quicker recovery and reduced side effects. Cryoablation has been utilized on a limited basis for the treatment of PDAC. With the recent reports on the success of cryoablation, there is a growing interest in the use of cryoablation as a standalone, minimally invasive procedure to treat PDAC. While offering a promising path, the application of cryoablation to PDAC is limited by current technologies. As such, there is a need for the development of new devices to support advanced treatment strategies for PDAC. To this end, this study investigated the performance of a new endoscopic ultrasound-compatible cryoablation catheter technology, FrostBite. We hypothesized that FrostBite would enable the rapid, effective, minimally invasive delivery of ultra-cold temperatures to target tissues, resulting in effective ablation via an endoscopic approach. Thermal properties and ablative efficacy were evaluated using a heat-loaded gel model, tissue-engineered models (TEMs), and an initial in vivo porcine study. Freeze protocols evaluated included single and repeat 3 and 5 min applications. Isotherm assessment revealed the generation of a 2.2 cm diameter frozen mass with the -20 °C isotherm reaching a diameter of 1.5 cm following a single 5 min freeze. TEM studies revealed the achievement of temperatures ≤ -20 °C at a diameter of 1.9 cm after a 5 min freeze. Fluorescent imaging conducted 24 h post-thaw demonstrated a uniformly shaped ellipsoidal ablative zone with a midline diameter of 2.5 cm, resulting in a total ablative volume of 6.9 cm3 after a single 5 min freeze. In vivo findings consistently demonstrated the generation of ablative areas measuring 2.03 cm × 3.2 cm. These studies demonstrate the potential of the FrostBite cryocatheter as an endoscopic ultrasound-based treatment option. The data suggest that FrostBite may provide for the rapid, effective, controllable freezing of cancerous pancreatic and liver tissues. This ablative power also offers the potential of improved safety margins via the minimally invasive nature of an endoscopic ultrasound-based approach or natural orifice transluminal endoscopic surgery (NOTES)-based approach. The results of this pre-clinical feasibility study show promise, affirming the need for further investigation into the potential of the FrostBite cryocatheter as an advanced, minimally invasive cryoablative technology.

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Cold-induced injuries are a major challenge for burn surgeons, leading to significant sequelae for the patients including amputations, long-term disability, and death. Rapid assessment and diagnosis are essential for optimal outcomes. Various therapies have emerged to improve outcomes. Topical, oral, and intravenous agents have shown to minimize the impact of cold-induced injuries. Thrombolytics have shown the greatest promise in improving tissue perfusion outcomes in cold-induced injuries. This article provides an update on the evidence-based assessment and management of cold-induced injuries, as well as reviews outcomes and future directions of this challenging pathology.

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BACKGROUND: Accidental hypothermia with severe frostbite is a rare combination of injuries with a high risk for long-term sequelae. There are widely accepted recommendations for the management of avalanche victims and for frostbite treatment, but no recommendation exists for the treatment of frostbite in severe hypothermic patients, specifically for the management of hypothermic avalanche victims presenting with frostbite. CASE PRESENTATION: We present a case of a previously healthy, 53-year-old male skier who was critically buried by an avalanche at 2300 m of altitude at an ambient temperature of - 8 °C for nearly 23 h. The victim was found with the right hand out of the snow and an air connection to outside. He was somnolent with Glasgow Coma Scale 11 (Eye 4, Verbal 2, Motor 5) and spontaneously breathing, in a severely hypothermic state with an initial core temperature of 23.1 °C and signs of cold injuries in all four extremities. After rescue and active external forced air rewarming in the intensive care unit, the clinical signs of first-degree frostbite on both feet and the left hand vanished, while third- to fourth-degree frostbite injuries became apparent on all fingers of the right hand. After reaching a core body temperature of approximately 36 °C, aggressive frostbite treatment was started with peripheral arterial catheter-directed thrombolysis with alteplase, intravenous iloprost, ibuprofen, dexamethasone and regional sympathicolysis with a right-sided continuous axillary block. After ten months, the patient had no tissue loss but needed neuropathic pain treatment with pregabalin. CONCLUSION: The combination of severe accidental hypothermia and severe frostbite is rare and challenging, as drug metabolism is unpredictable in a hypothermic patient and no recommendations for combined treatment exist. There is general agreement to give hypothermia treatment the priority and to begin frostbite treatment as early as possible after full rewarming of the patient. More evidence is needed to identify the optimal dosage and time point to initiate treatment of frostbite in severely hypothermic patients. This should be taken into consideration by future treatment recommendations.

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A 19-year-old male presented with facial frostbite and severe oropharyngeal edema after prolonged riding of a snowmobile without any facial covering. The diffuse swelling eventually progressed to airway obstruction, requiring a surgical airway. No alternative explanation was found for his presentation, making this the first case found in the literature of airway obstruction secondary to environmental cold exposure.

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Frostbite, a debilitating condition, significantly affects the well-being of military veterans and high-altitude residents, causing severe clinical complications such as chronic pain that markedly impacts overall quality of life. There has been a notable increase in the development of pre-clinical models for studying frostbite injury, but their suitability for pain evaluation remains limited. The major hurdle in the development of novel therapeutics for the treatment of frostbite-induced chronic pain is the unavailability of well-established preclinical models. In this study, we employed deep-frozen magnets to induce frostbite injury and conducted validation for chronic pain through assessments of face, predictive, and mechanistic validity. Behavioral assays demonstrated that frostbite injury exhibited significant mechanical, thermal & cold hypersensitivity in rats. Further, molecular analysis indicated that frostbite injury triggered the activation of TRP channels (TRPA1, TRPV1 and TRPM8), microgliosis, and neuroinflammation in the dorsal root ganglion (DRG) and spinal cord of rats. Notably, NR2B protein expressions were significantly upregulated in the DRG of injured rats, while no changes were observed in spinal NR2B expressions. Furthermore, the administration of ibuprofen (25, 50, and 100 mg/kg, i.p.) resulted in a significant improvement in behavioral, biochemical, and molecular alterations in frostbite-injured rats. Overall, results suggested that established frostbite model effectively recapitulates face, pharmacological, and mechanistic validity, highlighting its potential for screening future treatment modalities and exploring the intricate mechanisms associated with frostbite-induced chronic pain.

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