Non-freezing Cold Injury Research Articles

Cold Environment-Associated Extremity Lesions or Severe Hypothermia Help Differentiate Between Frostbitten and Trench Foot (Immersion Foot).

Cold associated foot injuries, such as frostbite and trench foot (immersion foot) are relatively common in cold environments. The former is classified as a freezing cold injury, and the latter as a nonfreezing cold injury. Trench foot is sometimes misdiagnosed as frostbite, and rapid rewarming exacerbates the condition. This paper aims to help differentiate between frostbitten foot and trench foot. This study included patients with frostbitten foot or trench foot treated at our hospital between December 2005 and May 2023. The differences in sex, age, month of injury, conditions at the time of injury, injury distribution, foot lesion laterality, other complications upon arrival (finger frostbite, immersion hand, or hypothermia), and presence and distribution of sensory disturbance at discharge were noted among the groups. A total of 16 patients (14 men) with frostbitten foot and 3 patients (3 men) with trench foot were identified. Finger frostbite observed in nine and zero patients with frostbitten foot and trench foot, respectively; and severe hypothermia on arrival observed in five and zero patients with frostbitten foot and trench foot, respectively. Physical findings at the initial examination showed that the frostbitten feet were dry, and the lesions were distal and clearly demarcated, whereas feet with trench foot were wet, and the lesions covered the entire sole and were not clearly demarcated. Accurate differentiation between frostbitten foot and trench foot and appropriate initial treatment are important. The presence of finger frostbite, immersion hand or severe hypothermia may help to differentiate between frostbitten foot and trench foot.

Can iloprost be used for treatment of cold weather injury at the point of wounding in a forward operating environment? A literature review

ABSTRACT Introduction: Cold Weather Injury (CWI) represents a spectrum of pathology, the two main divisions being Freezing Cold Injury (FCI) and Non-Freezing Cold Injury (NFCI). Both are disabling conditions associated with microvascular and nerve injury often treated hours after initial insult when presenting to a healthcarestablishment. Given that iloprost is used for the treatment of FCI, could it be used in a forward operating environment to mitigate treatment delay? Is there a role for its use in the forward treatment of NFCI? This review sought to evaluate the strength of evidence for the potential use of iloprost in a forward operating environment. Methods: Literature searches were undertaken using the following question for both FCI and NFCI: in [patients with FCI/NFCI] does [the use of iloprost] compared to [standard care] reduce the incidence of [long-term complications]. Medline, CINAHL and EMBASE databases were searched using the above question and relevant alternative terminology. s were reviewed before full articles were requested. Results: The FCI search yielded 17 articles that were found to refer to the use of iloprost and FCI. Of the 17, one referred to pre-hospital treatment of frostbite at K2 base camp; however, this was utilising tPA. No articles referred to pre-hospital use in either FCI or NFCI. Discussion: Although evidence exists to support the use of iloprost in the treatment of FCI, its use to date has been in hospital. A common theme is delayed treatment due to the challenges of evacuating casualties from a remote location. There may be a role for iloprost in the treatment of FCI; however, further study is required to better understand the risk of its use.

Training videos to prevent cold weather injuries

ABSTRACT Cold weather injuries (CWIs) are a challenge during military training, exercises and operations in Arctic conditions. Soldier performance in these challenging conditions depends on protective equipment, knowledge, personal experience, routines, and leadership. Despite the Norwegian Armed Forces’ goal of zero freezing cold injuries (FCIs), there has been a persistently high incidence of FCIs among the younger soldiers with an average of 120–150 new FCIs recorded each year. Therefore, an expert working group with representatives from medical, defence and research background was established in 2020. Their task was to develop a communication package to help prevent CWIs among military personnel. Training videos and an updated and improved official website were created with a focus on practical recommendations and advice to prevent CWIs and especially FCIs. Risks, prevention and symptoms of FCIs were emphasised. The main goal of the training videos was to supplement current teaching on guidance for CWI prevention in CWOs to prevent FCIs, but following the advice may prevent non-freezing cold injuries (NFCIs) and hypothermia. This informative paper describes the background, working methods and possible implications of the training videos, which may be a potential way forward to improve cold weather training and operations.

Extremity cooling during an arctic diving training exercise

ABSTRACT A field study was conducted to examine the vulnerability of military divers to non-freezing cold injury (NFCI) during Arctic ice-diving operations. Participants were instrumented with temperature sensors on the back of their hands and on the bottom of their big toe for each dive to measure cooling of their extremities. While NFCI was not diagnosed in any of the participants during this field study, the data indicate that the feet were particularly vulnerable during the dives given that they were mostly in a temperature zone that could cause pain and performance decrements. The data also show that for short term dives, the dry and wet suits with wet gloves in both configurations were thermally more comfortable for the hands than the dry suit with dry glove configuration; however, the latter would be more protective against potential NFCI during longer dives. Features such as hydrostatic pressure and repetitive diving that are unique to diving but not previously considered as risk factors for NFCI are examined herein and warrant deeper investigation given that symptoms of NFCI might be mistaken as decompression sickness.

Peripheral sensory function in non-freezing cold injury patients and matched controls.

What is the central question of this study? Is peripheral sensory function impaired in the chronic phase of non-freezing cold injury (NFCI)? What is the main finding and its importance? Warm and mechanical detection thresholds are elevated and intraepidermal nerve fibre density is reduced in individuals with NFCI in their feet when compared to matched controls. This indicates impaired sensory function in individuals with NFCI. Interindividual variation was observed in all groups, and therefore a diagnostic cut-off for NFCI has yet to be established. Longitudinal studies are required to follow NFCI progression from formation to resolution ABSTRACT: The aim of this study was to compare peripheral sensory neural function of individuals with non-freezing cold injury (NFCI) with matched controls (without NFCI) with either similar (COLD) or minimal previous cold exposure (CON). Thirteen individuals with chronic NFCI in their feet were matched with the control groups for sex, age, race, fitness, body mass index and foot volume. All undertook quantitative sensory testing (QST) on the foot. Intraepidermal nerve fibre density (IENFD) was assessed 10cm above the lateral malleolus in nine NFCI and 12 COLD participants. Warm detection threshold was higher at the great toe in NFCI than COLD (NFCI 45.93 (4.71)°C vs. COLD 43.44 (2.72)°C, P=0.046), but was non-significantly different from CON (CON 43.92 (5.01)°C, P=0.295). Mechanical detection threshold on the dorsum of the foot was higher in NFCI (23.61 (33.59) mN) than in CON (3.83 (3.69) mN, P=0.003), but was non-significantly different from COLD (10.49 (5.76) mN, P>0.999). Remaining QST measures did not differ significantly between groups. IENFD was lower in NFCI than COLD (NFCI 8.47 (2.36) fibre/mm2 vs. COLD 11.93 (4.04) fibre/mm2 , P=0.020). Elevated warm and mechanical detection thresholds may indicate hyposensitivity to sensory stimuli in the injured foot for individuals with NFCI and may be due to reduced innervation given the reduction in IENFD. Longitudinal studies are required to identify the progression of sensory neuropathy from the formation of injury to its resolution, with appropriate control groups employed.

Plasma biomarkers of endothelial function, inflammation and oxidative stress in individuals with non-freezing cold injury.

What is the central question of this study? Are biomarkers of endothelial function, oxidative stress and inflammation altered by non-freezing cold injury (NFCI)? What is the main finding and its importance? Baseline plasma [interleukin-10] and [syndecan-1] were elevated in individuals with NFCI and cold-exposed control participants. Increased [endothelin-1] following thermal challenges might explain, in part, the increased pain/discomfort experienced with NFCI. Mild to moderate chronic NFCI does not appear to be associated with either oxidative stress or a pro-inflammatory state. Baseline [interleukin-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosis of NFCI. Plasma biomarkers of inflammation, oxidative stress, endothelial function and damage were examined in 16 individuals with chronic NFCI (NFCI) and matched control participants with (COLD, n=17) or without (CON, n=14) previous cold exposure. Venous blood samples were collected at baseline to assess plasma biomarkers of endothelial function (nitrate, nitrite and endothelin-1), inflammation [interleukin-6 (IL-6), interleukin-10 (IL-10), tumour necrosis factor alpha and E-selectin], oxidative stress [protein carbonyl, 4-hydroxy-2-nonenal (4-HNE), superoxide dismutase and nitrotyrosine) and endothelial damage [von Willebrand factor, syndecan-1 and tissue type plasminogen activator (TTPA)]. Immediately after whole-body heating and separately, foot cooling, blood samples were taken for measurement of plasma [nitrate], [nitrite], [endothelin-1], [IL-6], [4-HNE] and [TTPA]. At baseline, [IL-10] and [syndecan-1] were increased in NFCI (P<0.001 and P=0.015, respectively) and COLD (P=0.033 and P=0.030, respectively) compared with CON participants. The [4-HNE] was elevated in CON compared with both NFCI (P=0.002) and COLD (P<0.001). [Endothelin-1] was elevated in NFCI compared with COLD (P<0.001) post-heating. The [4-HNE] was lower in NFCI compared with CON post-heating (P=0.032) and lower than both COLD (P=0.02) and CON (P=0.015) post-cooling. No between-group differences were seen for the other biomarkers. Mild to moderate chronic NFCI does not appear to be associated with a pro-inflammatory state or oxidative stress. Baseline [IL-10] and [syndecan-1] and post-heating [endothelin-1] are the most promising candidates for diagnosing NFCI, but it is likely that a combination of tests will be required.

Investigating genotype-phenotype relationship of extreme neuropathic pain disorders in a UK national cohort.

The aims of our study were to use whole genome sequencing in a cross-sectional cohort of patients to identify new variants in genes implicated in neuropathic pain, to determine the prevalence of known pathogenic variants and to understand the relationship between pathogenic variants and clinical presentation. Patients with extreme neuropathic pain phenotypes (both sensory loss and gain) were recruited from secondary care clinics in the UK and underwent whole genome sequencing as part of the National Institute for Health and Care Research Bioresource Rare Diseases project. A multidisciplinary team assessed the pathogenicity of rare variants in genes previously known to cause neuropathic pain disorders and exploratory analysis of research candidate genes was completed. Association testing for genes carrying rare variants was completed using the gene-wise approach of the combined burden and variance-component test SKAT-O. Patch clamp analysis was performed on transfected HEK293T cells for research candidate variants of genes encoding ion channels. The results include the following: (i) Medically actionable variants were found in 12% of study participants (205 recruited), including known pathogenic variants: SCN9A(ENST00000409672.1): c.2544T>C, p.Ile848Thr that causes inherited erythromelalgia, and SPTLC1(ENST00000262554.2):c.340T>G, p.Cys133Tr variant that causes hereditary sensory neuropathy type-1. (ii) Clinically relevant variants were most common in voltage-gated sodium channels (Nav). (iii) SCN9A(ENST00000409672.1):c.554G>A, pArg185His variant was more common in non-freezing cold injury participants than controls and causes a gain of function of NaV1.7 after cooling (the environmental trigger for non-freezing cold injury). (iv) Rare variant association testing showed a significant difference in distribution for genes NGF, KIF1A, SCN8A, TRPM8, KIF1A, TRPA1 and the regulatory regions of genes SCN11A, FLVCR1, KIF1A and SCN9A between European participants with neuropathic pain and controls. (v) The TRPA1(ENST00000262209.4):c.515C>T, p.Ala172Val variant identified in participants with episodic somatic pain disorder demonstrated gain-of-channel function to agonist stimulation. Whole genome sequencing identified clinically relevant variants in over 10% of participants with extreme neuropathic pain phenotypes. The majority of these variants were found in ion channels. Combining genetic analysis with functional validation can lead to a better understanding as to how rare variants in ion channels lead to sensory neuron hyper-excitability, and how cold, as an environmental trigger, interacts with the gain-of-function NaV1.7 p.Arg185His variant. Our findings highlight the role of ion channel variants in the pathogenesis of extreme neuropathic pain disorders, likely mediated through changes in sensory neuron excitability and interaction with environmental triggers.

The peripheral vascular responses in non-freezing cold injury and matched controls.

What is the central question of this study? Does non-freezing cold injury (NFCI) alter normal peripheral vascular function? What is the main finding and its importance? Individuals with NFCI were more cold sensitive (rewarmed more slowly and felt more discomfort) than controls. Vascular tests indicated that extremity endothelial function was preserved with NFCI and that sympathetic vasoconstrictor response might be reduced. The pathophysiology underpinning the cold sensitivity associated with NFCI thus remains to be identified. The impact of non-freezing cold injury (NFCI) on peripheral vascular function was investigated. Individuals with NFCI (NFCI group) and closely matched controls with either similar (COLD group) or limited (CON group) previous cold exposure were compared (n=16). Peripheral cutaneous vascular responses to deep inspiration (DI), occlusion (PORH), local cutaneous heating (LH) and iontophoresis of acetylcholine and sodium nitroprusside were investigated. The responses to a cold sensitivity test (CST) involving immersion of a foot in 15°C water for 2min followed by spontaneous rewarming, and a foot cooling protocol (footplate cooled from 34°C to 15°C), were also examined. The vasoconstrictor response to DI was lower in NFCI compared to CON (toe: 73 (28)% vs. 91 (17)%; P=0.003). The responses to PORH, LH and iontophoresis were not reduced compared to either COLD or CON. During the CST, toe skin temperature rewarmed more slowly in NFCI than COLD or CON (10min: 27.4 (2.3)°C vs. 30.7 (3.7)°C and 31.7 (3.9)°C, P<0.05, respectively); however, no differences were observed during the footplate cooling. NFCI were more cold-intolerant (P<0.0001) and reported colder and more uncomfortable feet during the CST and footplate cooling than COLD and CON (P<0.05). NFCI showed a decreased sensitivity to sympathetic vasoconstrictor activation than CON and greater cold sensitivity (CST) compared to COLD and CON. None of the other vascular function tests indicated endothelial dysfunction. However, NFCI perceived their extremities to be colder and more uncomfortable/painful than the controls.

Trench foot and other non-freezing cold injuries (literature review)

Non-freezing cold injury is a general term that includes trench foot and immersion foot and is characterized by damage to the soft tissues, nerves, and vessels of the distal extremities as a result of long stay (usually two to three days or longer) in wet, cold (but not freezing: typically 0 to 15 °C) conditions. Trench foot syndrome primarily affects military personnel, fishermen, agricultural workers, travelers, and other segments of the population. In wartime, the number of such local cold injuries increases several times. Unfortunately, in domestic medical developments, this problem is practically not given due attention. Based on data from foreign literary sources and their own clinical experience, the authors were able to highlight the main patterns of pathogenesis and clinical picture of this pathological condition with justification of treatment tactic and preventive measures.

“Trench Foot” on the Banks of Lake Geneva: A Severe Case of Nonfreezing Cold Injury

Formerly known as “trench foot” or “immersion foot,” nonfreezing cold injury (NFCI) is a rare condition mainly seen among vulnerable groups. We report the case of a homeless male diagnosed with NFCI after having spent 2 days in rainy, cold weather. He presented with white, wrinkled feet and sensorimotor loss. Imaging revealed thrombosis of the leg arteries. No revascularization procedure was possible, and the patient developed soft tissue necrosis requiring bilateral transtibial amputation. Our case highlights the high morbidity linked with NFCI and the need for early recognition and treatment by medical health professionals along with the implementation of preventive measures.

Population Characteristics, Symptoms, and Risk Factors of Idiopathic Chilblains: A Systematic Review, Meta-Analysis, and Meta-Regression.

Chilblains/perniosis is a non-freezing cold injury causing painful inflammatory skin lesions. Its pathogenesis remains poorly understood because it is often studied as secondary to other underlying conditions. We systematically investigated the population characteristics, symptoms, and predisposing factors of chilblains in healthy adults exposed to cool/cold environments. We screened PubMed, Embase, and Cochrane Library, and we adopted PRISMA reporting guidelines (PROSPERO: CRD42021245307). The risk of bias was assessed by two independent reviewers (RTI item bank). Random-effects model meta-analyses were performed to calculate the pooled prevalence of histopathological features. Mixed-effects meta-regressions were used to assess other sources of between-study heterogeneity. Thirteen studies (477 patients) were included. Chilblains affect more women than men, up to 12% of the body skin surface, and most frequently, the hands and fingers. Meta-analyses of nine studies (303 patients) showed a frequent presence of perivascular lymphocytic infiltrate (81%), basal epidermal-cell layer vacuolation (67%), papillary dermal edema (66%), and perieccrine lymphocytic infiltrate (57%). Meta-regressions (p ≤ 0.05) showed that smoking and frequent occupational exposure to water increase the likelihood of histopathological features. The population characteristics, symptoms, and predisposing factors of chilblains revealed in this analysis should be incorporated in medical care to improve the condition's diagnosis and management.

Pediatric Environmental Cold Injuries.

Cold weather injuries are relevant concerns for children during winter sports and outdoor activities. To mitigate the risk of cold injury in this high-risk population, providers can educate parents on proper outdoor attire as well as the added risks of wind and water exposure. There are 2 types of environmental cold injuries: freezing injuries and nonfreezing injuries. Frostbite is a freezing injury from direct contact with cold air or surfaces. The extent of injury depends on the depth to which the freezing extends. Treatment involves rewarming the frozen tissue with warm water baths and considering analgesia. Hypothermia is a nonfreezing cold injury, and it can occur even when ambient temperatures are above freezing. When there is a decrease in the body's core temperature, hypothermia progresses from mild to severe symptoms. Treatment of hypothermia is threefold but is also dependent on the core body temperature, as colder core temperatures will require more aggressive warming techniques. Hypothermia treatment involves passive protection from further heat loss (ie, removing wet clothing), which helps the body to warm itself. Treatment also involves active external rewarming wherein a heat source, such as a heated blanket, is used to increase body temperature. Active internal rewarming is the delivery of heat inside the patient's body, such as warmed intravenous fluids.

Nonfreezing Cold Injury and Cold Intolerance in Paddlesport.

Nonfreezing cold injury (NFCI) occurs when tissues are subjected to prolonged cooling that causes tissue damage, but not freezing. Long-term effects include cold intolerance, with allodynia, pain, or numbness of the affected limb. Those who participate in outdoor paddlesports are at particular risk. This is an epidemiological study that aimed to determine the risk factors for paddlesport athletes developing NFCI and chronic cold intolerance in their hands. Secondary outcomes were to correlate cumulative cold exposure with the development of cold intolerance and to identify risk factors for developing NFCI or cold intolerance. Six hundred nine athletes responded to a survey distributed by their national governing body obtaining demographic and activity details, symptoms of NFCI, and a cold intolerance severity score (CISS). Twenty-three percent reported symptoms consistent with acute NFCI. The median CISS was 31 y (interquartile range 25-43), and 15% had a pathological CISS defined as >50. Females and individuals with Raynaud's phenomenon or migraines had a significantly higher CISS (P<0.05). Regression analysis found that females, smokers, and those with Raynaud's phenomenon or a previous nerve injury had a significantly higher risk of developing pathological cold intolerance (CISS >50). There was no correlation between cumulative cold exposure and CISS. A large proportion of paddlesport athletes undertaking activity in cold conditions have a pathological CISS or episodes consistent with NFCI. Cumulative cold exposure was not associated with a pathologically high CISS. The risk factors were female sex, smokers, and those suffering from either Raynaud's phenomenon or nerve injury.

Cold Weather Injuries: Initial Evaluation and Management.

As more people take to extreme sporting activities and hobbies, the sports medicine physician should be proficient in early identification and initial sideline or field management of cold weather injuries. There is significant mortality and morbidity associated with these conditions. The most severe of these are hypothermia and frostbite, which have limited evidence for their field management. Nonfreezing cold injuries and chilblains are much rarer, although appropriate prevention and treatment strategies can be used to minimize harm to athletes. This article will provide the most updated recommendations for field or sideline evaluation and initial management of hypothermia, frostbite, nonfreezing cold injury, and chilblains.

Delayed rehabilitation in non-freezing cold injury results in increased pain and reduced quality of life in military personnel

Delayed rehabilitation in non-freezing cold injury results in increased pain and reduced quality of life in military personnel

Hypothermia and Cold Injury in Children.

Hypothermia and Cold Injury in Children.

Nonfreezing Cold Injury (Trench Foot).

Nonfreezing cold injury (NFCI) is a modern term for trench foot or immersion foot. Moisture is required to produce a NFCI. NFCI seldom, if ever, results in loss of tissue unless there is also pressure necrosis or infection. Much of the published material regarding management of NFCIs has been erroneously borrowed from the literature on warm water immersion injuries. NFCI is a clinical diagnosis. Most patients with NFCI have a history of losing feeling for at least 30 min and having pain or abnormal sensation on rewarming. Limbs with NFCI usually pass through four ‘stages.’ cold exposure, post-exposure (prehyperaemic), hyperaemic, and posthyperaemic. Limbs with NFCI should be cooled gradually and kept cool. Amitriptyline is likely the most effective medication for pain relief. If prolonged exposure to wet, cold conditions cannot be avoided, the most effective measures to prevent NFCI are to stay active, wear adequate clothing, stay well-nourished, and change into dry socks at least daily.

Thermoregulatory and Metabolic Demands of Naval Special Warfare Divers During a 6-h Cold-Water Training Dive.

Introduction: Extreme environmental conditions induce changes in metabolic rate and substrate use due to thermoregulation. Cold-water full-body submersion for extended periods of time is inevitable for training and missions carried out by Naval Special Warfare divers. Anthropometric, physiologic, and metabolic data have been reported from partial immersion in cold water in non-thermally protected men; data is limited in thermally protected divers in extremely cold water. Thermoregulatory and metabolic demands during prolonged cold-water submersion in Naval Special Warfare divers are unknown.Objective: Assess thermoregulatory and metabolic demands of Naval Special Warfare divers surrounding prolonged cold-water submersion.Materials and Methods: Sixteen active-duty U.S. Navy Sea Air and Land (SEAL) operators tasked with cold-water dive training participated. Divers donned standard military special operations diving equipment and fully submerged to a depth of ∼ 6 m in a pool chilled to 5°C for a 6-h live training exercise. Metabolic measurements were obtained via indirect calorimetry for 10-min pre-dive and 5-min post dive. Heart rate, skin temperature, and core temperature were measured throughout the dive.Results: Core temperature was maintained at the end of the 6-h dive, 36.8 ± 0.4°C and was not correlated to body composition (body fat percentage, lean body mass) or metabolic rate. SEALs were not at risk for non-freezing cold injuries as mean skin temperature was 28.5 ± 1.6°C at end of the 6-h dive. Metabolic rate (kcal/min) was different pre- to post-dive, increasing from 1.9 ± 0.2 kcal/min to 2.8 ± 0.2 kcal/min, p < 0.001, 95% CI [0.8, 1.3], Cohen’s d effect size 2.3. Post-dive substrate utilization was 57.5% carbohydrate, 0.40 ± 0.16 g/min, and 42.5% fat, 0.13 ± 0.04 g/min.Conclusion: Wetsuits supported effective thermoprotection in conjunction with increase in thermogenesis during a 6-h full submersion dive in 5°C. Core temperature was preserved with an expected decrease in skin temperature. Sustained cold-water diving resulted in a 53% increase in energy expenditure. While all participants increased thermogenesis, there was high inter-individual variability in metabolic rate and substrate utilization. Variability in metabolic demands may be attributable to individual physiologic adjustments due to prior cold exposure patterns of divers. This suggests that variations in metabolic adjustments and habituation to the cold were likely. More work is needed to fully understand inter-individual metabolic variability to prolonged cold-water submersion.

Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration.

Introduction: Neuropathic pain associated with Non-freezing Cold Injury (NFCI) is a major burden to military service personnel. A key feature of NFCI is reduction of the intra-epidermal nerve fibre density in skin biopsies, in keeping with painful neuropathy. Current oral treatments are generally ineffective and have undesirable side effects. Capsaicin 8% patch (Qutenza) has been shown to be well-tolerated and effective for reducing neuropathic pain, for up to 3 months after a single 30-minute application.Methods: In this single-centre open label study, 16 military participants with NFCI (mean duration 49 months) received 30-minute Capsaicin 8% patch treatment to the feet and distal calf. Pain symptoms were assessed using a pain diary (with the 11-point Numerical Pain Rating Scale, NPRS) and questionnaires, the investigations included skin biopsies, performed before and three months after treatment.Results: Participants showed significant decrease in spontaneous pain (mean NPRS: −1.1, 95% CI: 0.37 to 1.90; p = 0.006), and cold-evoked pain (−1.2, 95% CI: 0.40 to 2.04; p = 0.006). The time-course of pain relief over 3 months was similar to other painful neuropathies. Patient Global Impression of Change showed improvement (p = 0.0001).Skin punch biopsies performed 3 months after the patch application showed significant increase of nerve fibres with structural marker PGP9.5 (intra-epidermal nerve fibres [IENFs], p < 0.0001; sub-epidermal nerve fibres [SENFs]; p =< 0.0001), and of regenerating nerve fibres with their selective marker GAP43 (p = 0.0001). The increase of IENFs correlated with reduction of spontaneous (p = 0.027) and cold-evoked pain (p = 0.019).Conclusions: Capsaicin 8% patch provides an exciting new prospect for treatment of NFCI, with regeneration and restoration of nerve fibres, for the first time, in addition to pain relief.

Successful Recovery of Peripheral Polyneuropathy from Non-Freezing Cold Injury: A Case Report

Successful Recovery of Peripheral Polyneuropathy from Non-Freezing Cold Injury: A Case Report