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CHRONIC PAIN

Fibromyalgia (FM) is a chronic widespread pain disorder. The allodynia and hyperalgesia induced by an imbalance in the level of the neurotransmitters and in  pro- and anti-inflammatory mediators are  the sources of neurological pain. Fibromyalgia involves fatigue, sleep problems and other frequent comorbid physical and mental disorders (Trinanes et al. 2014).

A study has already demonstrated that patients with FM treated with WBC  report an  improvement  in quality of life (Bettoni et al. 2013). This study was conducted with 50 patients with FM. The WBC treatment protocol consisted of 15 sessions over a period of 3 weeks. Each session duration was 30 s at - 60°C and 3 min at under - 100°C. In this study, a VAS was used to measure pain and a self-assessment questionnaire regarding global health status was used to calculate the disease activity score. A qualitative score of the physical and mental health of the patients with FM was obtained via the Short Form Health Survey (SF-36). Fatigue was evaluated with the Fatigue Severity Scale. The findings showed a positive effect of WBC on the quality of life of a group of patients with FM as demonstrated by improvements in all the qualitative indexes. The authors speculated that improvement was due to the effects of cryotherapy on the balance between pro- and anti-inflammatory mediators, which have a role in the modulation of pain (Lubkowska et al. 2010, 2011; Bettoni et al. 2013).

Link to  http://wholebody-cryotherapy.com/en/cryotherapy/chronic-pains.html 

ANTIOXIDANT STATUS

FIG. 2. THE EFFECT OF WHOLE-BODY CRYOSTIMULATION (WBCT) ON THE LEVEL OF THIOBARBITURIC ACID REACTIVE SUBSTANCES (TBARS) IN PLASMA. WBCT STUDY GROUP BEFORE (WBCT-0) AND AFTER 10 DAYS OF CRYOSTIMULATION (WBCT-10); NON-WBCT CONTROL SUBJECTS AT THE START OF THE EXPERIMENT (CONT.-0) AND 10 DAYS LATER (CONT.-10); ERROR BARS INDICATE STANDARD DEVIATION (SD). (*P <0.05, **P < 0.01, ***P <0.001) ADAPTED FROM MILLER ET AL. 2012.

Physical exercise is known to be characterised by an increase in oxygen consumption, and consuming high levels of oxygen is associated with increased free radical production (Sen 1995). Modulation of oxygenated free radical production plays a clear role in muscle recovery after exercise (Gauché et al. 2006). High intensity exercise and/or exercise involving many eccentric movements are a true stress, producing metabolic by-products with significant effects on cellular structures. Oxygen-derived free radical species (ODFR) – involved in oxidative stress – are of various structures, but all are extremely reactive compounds which, once produced, will oxidise various cellular components. This oxidation can lead to cellular dysfunction and, among other things, to inflammatory disorders. WBC has sometimes been used to reduce oxidative stress. The first studies were carried out by Siems and Brenke (1992), and showed that acute exposure to WBC, between 1 and 5 minutes, caused oxidative stress in experienced swimmers. One hour after exposure to cold, the intra-erythrocyte oxidised glutathione – a marker of oxidative stress – concentration had increased significantly more in subjects exposed to WBC than in a control group. This was combined with reduced concentrations of uric acid, a true scavenger of reactive oxygen species (Ames et al. 1982). Because of this, the authors suggested that the global increase in anti-oxidant protection resulted, in the long term, from repeated exposure to mild oxidative stress. In addition, during cooling and stimulation of the body, mitochondria exposed to low temperatures produce ten times more superoxide anions, as a result of increased lipid peroxidation (Bartosz 2003). A recent study by Dugué et al. (2005) showed increased total plasma antioxidant capacity (TPA) after three weekly cold room sessions at -110 °C for twelve weeks.

Several studies have measured the effets of single or repeated WBC sessions on oxidative stress and antioxidant function. However, the results were heterogeneous and suffered from several methodological biases, making it difficult to exploit them. Thus, in a study comparing two untrained groups, one of which was regularly exposed to intense cold by WBC, the other not, an increase in the antioxidant status of the first group was observed (see Fig. 2). In contrast, a very minor difference in lipid peroxidation was noted between the groups (Miller et al. 2012). Another crossed randomised study of trained canoeists reported a reduction in oxidative stress after 10 days’ training in the WBC condition compared to the control condition (Mila-Kierzenkowska et al. (2009). However, the enzymatic profiles for the athletes involved in this study were quite unusual and a high degree of inter-individual variation was noted. This result raises significant questions about the relevance of the conclusions that can be drawn from this study. Nevertheless, most studies show an increase in the body’s antioxidant capacity when it is regularly exposed to very intense cold. In the context of exercise, some authors suggest that the use of WBC as a recovery method could help promote a balance between pro- and antioxidant reactions, in particular during periods when the training workload is being increased. Nevertheless, several questions remain, among which whether maintaining this equilibrium is an advantage if the objective sought is to promote adaptations to training. In this case, an imbalance could, to a certain extent, act as a stimulant.

THE AUTONOMIC NERVOUS SYSTEM (ANS)

II. 3. - The autonomic nervous system (ANS)

Few studies have addressed the question of how WBC affects the nervous system. However, these few studies all indicated that WBC modified the activity of the autonomous nervous system. A French team, in particular, showed that a 3-min exposure to very intense cold increased the activity of the autonomous nervous system with a predominance of the parasympathetic branch (Hausswirth et al. 2013). In this study, the increase in sympathetic activity was measured through an increase in plasma catecholamine concentrations, while a reduction in heart rate associated with an increase in indicators of cardiac variability indicated an increase in parasympathetic activity. According to the authors, the effect on parasympathetic activity is greater with WBC at -110 °C than with partial cryotherapy, suggesting that a signficant reduction in skin temperature is necessary to maximally stimulate the autonomous nervous system. Similar results were reported in training conditions, with an increase in parasympathetic reactivation after exhausting exercise followed by a WBC session (Schaal et al. 2013). The control group in this study used a passive recovery method. Although not extensively studied, the influence of WBC on the activity of the autonomous nervous system, and in particular on parasympathetic activity, is essential as parasympathetic activity is directly implicated in human recovery and strongly correlated with sleep quality and life expectancy. New questions thus arise, in particular how long the effects of WBC on the autonomous nervous system last. Are these effects transitory? Are they influenced by the number of daily exposures? Are they affected by temperature?

Numerous studies have accumulated scientific evidence supporting the beneficial effects of WBC in the medical domain - when used as an alternative treatment or rehabilitation technique - and in the sporting realm - especially in the context of post-exercise recovery. However the physiological mechanisms responsible for the effects of extreme cold exposure remain unclear and no consensus on a scientifically-determined optimal cryotherapy protocol has yet been reached. In a recently published work, it was showed that stimulation of the autonomic nervous system after a single whole-body cryostimulation session was more pronounced when subjects used a cryotherapy system (exposing the whole body to air at -110 °C air) compared to an open tank (exposing the whole body except the head to expanded nitrogen gas at -160 °C) (Hausswirth et al. 2017). The cryochamber icelab -110 °C was found to induce the greatest overall decrease in skin temperature, thus raising the question of whether the physiological adaptations to cryotherapy were induced by cold intensity or exposure of the head to cold. We went on to study the specific/isolated influence of exposing the head to cold during five daily cryostimulation sessions causing a similar decrease in skin temperature (Louis et al. 2015). Exposure of the body to cold is an effective method to easily and rapidly increase parasympathetic activity, and greater effects are obtained using air-based cryotherapy protocols than with cold water immersion. Two main modalities of air-based cryotherapy exist: in one, the head is exposed, while in the other it is not. Thus, these results give indications as to the usefulness of these different techniques and information on the physiological mechanisms involved. The last results indicated that both cryotherapy techniques triggered parasympathetic stimulation with some marked effects on recorded variables due specifically to head cooling. These results suggest that the intensity of the autonomic response (i.e., parasympathetic stimulation) is mainly proportional to the intensity of cold experienced. It is also possible that the short-lived exposure to cold (3 min) in cryotherapy may not be sufficient to trigger parasympathetic stimulation through the trigeminal nerve endings, as trigeminal afferents are mostly unmyelinated fibres, suggesting that there is a certain latency in their response (Khurana et al. 1997). A predominance of parasympathetic tone was recorded from the first to the fifth WBC sessions, with small differences between groups in the magnitude of the response.

DEPRESSION AND MENTAL STATE

Depression and mental state

Some studies investigated the somatic and psychological effects of cold and seemed to reach a consensus on mood alterations. Somatic and psychological parameters seem somewhat linked to the topic of preventing burn-out in working. Thus, the first study on the subject showed that a short exposure to WBC improved sleep, sense of relaxation and mood, and that these effects can persist for hours, or even days (Gregorowicz and Zagrobelny 1998). In a more recent study, Rymaszewska et al. (2003) studied the effects of WBC (under -100 °C, 160 seconds, ten times over two weeks) in twenty-three depressed patients on anti-depressant treatment. Using the twenty-one items on the "Hamilton Depression Rating Scale" (HRDS), the authors concluded that WBC exposure had a positive effect on HRDS scores, and thus helped alleviate symptoms of depression. Given these results, the authors very recently published another study, similar to their previous work, but which included a control group of thirty-four patients (Rymaszewska et al. 2008). After three weeks, the HRDS scores for the twenty-six patients suffering from depression were reduced by 34.6% in the WBC group, against only 2.9% in the control group. One neurobiological hypothesis states that depression results from a deregulation of the hypothalamic-pituitary-adrenal (HPA) axis [hypothalamo-hypophyso-adrenergic axis]. The authors relate the improved mood regulation and HRDS scores to this axis. In addition, it seems that WBC also has positive effects on patients' biological rhythms. All these results could provide some help for the temporary psychological problems frequently encountered by people during working.

In another recent study (Szczepańska-Gieracha et al. 2013) on mental state and quality of life, a positive impact of WBC on different aspects of general wellbeing (both somatic and psychological) and the quality of life was confirmed. Results showed that the greater the problems of the patients before the commencement of therapy (in terms of their mood and well-being), the stronger the effects of WBC. This is evident in the group of women who, at the first measurement, reported much more severe symptoms of anxiety, and worse general well-being than men. At the same time, their improvement in all the analyzed parameters after 10 WBC sessions was more dynamic than that of men. In addition to that, patients suffering from depression are not able to force themselves to carry out daily physical exercise. Attempting to limit their pain, they avoid physical activity, which worsens their condition, increases their discomfort and mental tension, and consequently accelerates the progression of the disease. The strong influence of WBC on the mental state encourages its use in typically psychiatric disorders, particularly depression, where it could be used in addition to an applied therapy, or in cases where the current therapy does not bring desired effects.

RESPIRATORY FUNCTION

II. 5. - Respiratory function

The incidence of exposure to cold ambient temperatures on respiratory function has been the focus of several studies. The body is known to react to cold by stimulating the sympathetic nervous system, thus inducing bronchodilation (Marieb 1999). Bandopadhyay and Selvamarthy (2003) studied respiratory function in ten subjects exposed to Arctic cold for nine weeks. The results showed that the forced expiratory volume per second (FEV1) was significantly reduced in the first few days, and recovered its initial level after four weeks of exposure. At the end of the nine weeks, the authors observed a significant improvement in FEV1, but this is not maintained over time. This respiratory consequences of exposure to cold were recently studied by Smolander et al. (2009), who subjected twenty-five non-smokers to WBC. The subjects underwent three 2-minute WBC sessions per week for twelve weeks. Peak Flow (PF) and FEV1 were measured 2 and 30 minutes after each session. No change in PF or FEV1 (measured 2 minutes after the sessions) was recorded over the three months of the study. On the other hand, for measurements performed 30 minutes after sessions, PF and FEV1 values were significantly reduced by the end of the first month. The authors explained that the sympathetic effect, a reflex to the cold, seemed to return to basal levels after 30 minutes, when the parasympathetic system becomes more active. The authors concluded that WBC should be used with care in people with respiratory problems.

RHEUMATIC AND CENTRAL NERVOUS SYSTEM (CNS) DISEASES

II. 6. - Rheumatic and central nervous system (CNS) diseases

Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic connective tissue disease whose etiology is not fully understood. RA is more frequently observed in women and elderly people. The disease is characterized by nonspecific inflammation of the symmetrical joints, the occurrence of extra-articular changes, and organ damage that leads to disability and premature death (Aletaha et al. 2010). The destruction of the joints is different for each patient, and it is impossible to predict its progress (Badolato et al. 1996).The consequences of ongoing RA are pain, impaired physical function, and fatigue, which cause limitations in physical functioning and work disabilities, and finally adversely affect the health-related quality of life. One of the main symptoms of RA is pain, which, as highlighted by many authors, predominantly restricts all aspects of life (Collins et al 1997). Gizinska  et al. (2015) showed a significant improvement in pain severity, results which are consistent with the results of other authors who drew attention to the significant analgesic efficacy of physiotherapy treatments, including systemic cryotherapy (Häkkinen et al. 2005) and local (Jastrzabek et al. 2013) treatments for RA. Also, Hirvonen et al. (2006) compared local and WBC treatments, and significantly better results in pain sensation were obtained in the group treated with systemic cryotherapy. The authors pointed out that, despite the high efficiency and a small percentage of reported side effects, WBC treatment is the expensive and available only in properly prepared specialized centers.

 

Ankylosing spondylitis (AS) is a chronic, usually progressive inflammatory rheumatic disease affecting primarily the axial skeleton and sacroiliac joints. It usually begins in the second or third decade of life and tends to occur more often in males with a male to female ratio of roughly 2 to 1. Chronic spinal inflammation can develop a complete fusion of the vertebrae, a process called ankylosis, which causes total loss of mobility of the spine. In addition, AS may affect peripheral joints, the skin, eyes, bowel, or lungs (Braun et al. 2007). The main symptoms of the disease are pain and stiffness in the low back, upper buttock area, neck, and the remaining regions of the spine, which may lead to structural and functional impairments (Gran et al. 1997). One of the most significant effects of cryogenic temperatures is the analgesic effect connected with influence of low temperatures on endocrine system (increased secretion of

IMMUNE RESPONSES

II. 7. - Immune responses

Due to many studies on the topic, WBC is not associated with alterations to immunological markers, and it does not appear to have a detrimental effect on the immune system. Other data suggest that WBC does not impact immunological parameters, although the period of observation in this study was too short to assess modifications to lymphocyte involvement and function. In fact, subjecting healthy males to prolonged cold exposure resulted in slight increases in plasma tumour necrosis factor-a levels, and lymphocyte and monocyte counts. There is thus limited evidence that short- or long-lived exposure to cold causes immunosuppression. Rather, cold exposure has an immunostimulating effect possibly related to the enhanced noradrenaline (norepinephrine) response triggered by cold. Therefore, a stimulating effect of cold exposure could be argued. This effect is regulated by the relationship between the decrease in core temperature and the duration of exposure.

For a number of years, the immune system has been of particular interest to sports physiologists. The incidence of sore throats in very fit athletes initially helped doctors to detect overtraining syndrome. These intuitions were confirmed more recently by some very well run American and UK studies. In this context, Nieman (1994) observed that the immune response was impaired during repeated phases of prolonged high-intensity exercise, and that athletes responded poorly to bacterial and viral attacks, thus delaying recovery. Excessive sensitivity to respiratory tract infections seems to set in gradually, although it is well described that the risk of respiratory infection follows a "J-shaped" curve when plotted against training intensity, and that moderate exercise results in a low risk. Training is known to improve the immune response to a certain degree, while overworked athletes have reduced immune responses, in particular for immunoglobulins, "Natural Killer" or "NK" lymphocyte subgroups. While no study deals with the kinetics of how the immune system evolves after exposure to WBC, mainly because the procedure is so new, models involving swimming and immersion in cold water have been used for the last few years in Nordic countries, and have provided indications on how the immune system is affected. This practice, which was developed more on a cultural than on a scientific basis, has always been empirically linked to improved resistance to infections. In this context, Janský et al. (1996) carried out a six-week study on the effects of immerging ten patients in water at 14 °C for an hour three times per week. Looking at several markers of immunity, the authors observed a significant increase in CD25+ lymphocytes and CD14+ monocytes. Interleukin-6 (IL-6), a factor stimulating T lymphocyte production, was also shown to increase, but not significantly. Although it lacked a control group, this preliminary study indicated a possible stimulation of the immune system by limited (under one hour) exposure to cold. These results were reinforced by a study comparing populations swimming regularly in cold water or not (Dugué and Leppänen (1999)). Plasma IL-6 levels, monocytes and leukocytes were all higher in cold-water swimmers. The authors concluded that the immune system of cold-water swimmers was controlled the inflammatory response better and that repeated exposure to cold (by immersion or not) could explain the improvement in defence against infections. It could therefore be suggested that repeated exposure in cold rooms (i.e. WBC) stimulates the immune system and reduces susceptibility to infections in acclimatised individuals. New studies on WBC should shed light on these hypotheses and offer insights into the relationships between immunity, cold and athlete recovery.

COOLING AND COGNITION

II. 8. - Cooling and cognition

Whilst cooling is well known to reduce exercise-induced physiological strain, encountered in the heat, an as yet unknown area relates to the role of cooling to counter the exacerbated cognitive stress from exposure to the heat. Such responses seem to apply to all cognitive processes, including simple reaction time tasks through to more demanding cognitive interpretation and processing tasks. For example, simple reaction times were found to decrease when core temperature (i.e. Tcore) increased; highlighting a speeding effect from endogenous heat load on low-demand tasks (Parsons, 1993). Moreover, heat-related cognitive responses observed in complex computations also appeared magnified. When passive heating led Tcore to a light elevation (38.2°C), the power of attention was shown to increase both on simple and choice reaction times and complex (vigilance) cognitive tests (Simmons et al. 2008). The consistency of this result across the variety of tasks completed suggests that a rise in body temperature may induce a systematic improvement in the capacity to intensively (but punctually) concentrate on a stimulus. 

In addition, the decrease in thermal comfort leads the participant to perceive as greater the difficulty to respond to a given demand, compared to temperate conditions. Consequently, the athlete may deliberately invest greater cognitive resources into tasks completion, in order to compensate for or even counterbalance his/her heat-related perception (Razmjou, 1996). When Tcore values exceed 38.7°C, the literature suggests that the degree of hyperthermia and task complexity interact to determine the pattern of cognitive performance impairment (Amos et al., 2000). Indeed, at a Tcore of 39°C, both Racinais et al. (2008) and Gaoua et al. (2011) reported a negative effect of hyperthermia specific to complex tasks i.e. working memory capacity and recognition. The delay before subjects became more impulsive became shorter, from 20 to 7 minutes (Gaoua et al., 2011).

Similar to long term strategies, all short term procedures that can decrease heat strain will benefit mental processes and in turn, the resulting behavioural regulation. In this context, several practices must be considered and combined to magnify their respective effect. First, cooling procedures have been largely employed before competition, and have been shown to reduce Tcore, improve thermal sensations and demonstrated their usefulness on performance (Duffield et al. 2010). Further, cooling the head and the neck in hyperthermic conditions was found to eclipse heat-related debilitative effect on short-term memory and search and memory performances, such that performances returned to baseline (Gaoua et al., 2011 and Lee et al., 2013, respectively). From a practical view, such processes are necessary when considering relevant information before opting for a decision in pacing strategies, for example. Further, despite localized head and/or neck cooling does not appear to consistently act on Tcore reduction (Simmons et al. 2008), this type of cooling is systematic in decreasing perceived exertion during a specific action and/or exercise, and may thus act for people to push themselves higher into mental/cognitive effort. In this perspective, among different brain areas, specifically employing forehead (front) cooling seems to provide the most beneficial effect to reduce thermoregulatory responses in hot environment (Katsuura et al. 1996), and directly benefit complex, prefrontal cortex -dependent tasks in hot conditions. These concepts are highly relevant for sport performance, knowing that brain temperature becomes higher than Tcore in hyperthermic conditions (Nybo et al., 2002). 

In this context, Whole body cryotherapy led to significant improvements in memory task (Rymazewska et al. 2008) and significant but less durable reductions in depressive symptoms among people with mild cognitive impairment in a small, uncontrolled trial. Pre-cooling strategy using WBC before a memory task could be an opportunity to preserve cognitive functions and accomplish new challenges at work and/or in a heat context. Further studies need to confirm this hypothesis.