Whole Body Cryostimulation: A New Adjuvant Treatment in Central Sensitization Syndromes? An Expert Opinion.

Central sensitisation is defined as a multifactorial etiopathogenetic condition involving an increase in the reactivity of nociceptive neurons and alterations in pain transmission and perception in the central nervous system. Patients may present with widespread chronic pain, fatigue, sleep disturbance, dizziness, psychological (e.g., depression, anxiety, and anger) and social impairment. Pain can be spontaneous in onset and persistence, characterised by an exaggerated response and spread beyond the site of origin, and sometimes triggered by a non-painful stimulus. Whole-body cryostimulation (WBC) could be an adjuvant therapy in the management of this type of pain because of its global anti-inflammatory effect, changes in cytokines and hormone secretion, reduction in nerve conduction velocity, autonomic modulation, and release of neurotransmitters involved in the pain pathway. In several conditions (e.g., fibromyalgia, rheumatoid arthritis, and chronic musculoskeletal pain), WBC affects physical performance, pain perception, and psychological aspects. Given its multiple targets and effects at different organs and levels, WBC appears to be a versatile adjuvant treatment for a wide range of conditions of rehabilitation interest. Further research is needed to fully understand the mechanisms of analgesic effect and potential actions on pain pathways, as well as to study long-term effects and potential uses in other chronic pain conditions.

Catastrophizing, Kinesiophobia, and Acceptance as Mediators of the Relationship Between Perceived Pain Severity, Self-Reported and Performance-Based Physical Function in Women with Fibromyalgia and Obesity.

Purpose: Individuals with fibromyalgia and obesity experience significant impairment in physical functioning. Pain catastrophizing, kinesiophobia, and pain acceptance have all been identified as important factors associated with the level of disability. The objective of this study was to evaluate the role of pain catastrophizing, kinesiophobia, and pain acceptance as mediators of the association between perceived pain severity and physical functioning in individuals with fibromyalgia and obesity. Patients and Methods: In this cross-sectional study, 165 women with fibromyalgia and obesity completed self-report questionnaires of perceived pain severity (ie, Numeric Pain Rating Scale), pain catastrophizing (ie, Pain Catastrophizing Scale), kinesiophobia (ie Tampa Scale of Kinesiophobia), pain acceptance (ie, Chronic Pain Acceptance Questionnaire), and perceived physical functioning (ie, Physical Functioning subscale of the Fibromyalgia Impact Questionnaire). In addition, a performance-based test (ie, 6-minute walking test) was conducted to assess objective physical functioning. Two multiple mediation analyses were performed. Results: Pain acceptance and kinesiophobia mediated the relationship between pain severity and self-reported physical functioning. Pain catastrophizing and kinesiophobia mediated the relationship between pain severity and performance-based functioning. Conclusion: Pain acceptance, kinesiophobia, and pain catastrophizing should be addressed in rehabilitative intervention to improve physical functioning. Interestingly, the subjective and objective aspects of physical functioning are influenced by different factors. Therefore, interventions for women with fibromyalgia and obesity should focus on factors related to both subjective and performance-based physical functioning.

Is Whole-Body Cryostimulation an Effective Add-On Treatment in Individuals with Fibromyalgia and Obesity? A Randomized Controlled Clinical Trial.

Pain severity, depression, and sleep disturbances are key targets for FM rehabilitation. Recent evidence suggests that whole-body cryostimulation (WBC) might be an effective add-on treatment in the management of FM. The purpose of this study was to evaluate the effects of an add-on WBC intervention to a multidisciplinary rehabilitation program on pain intensity, depressive symptoms, disease impact, sleep quality, and performance-based physical functioning in a sample of FM patients with obesity. We performed a randomized controlled trial with 43 patients with FM and obesity undergoing a multidisciplinary rehabilitation program with and without the addition of ten 2-min WBC sessions at -110 °C over two weeks. According to our results, the implementation of ten sessions of WBC over two weeks produced additional benefits. Indeed, both groups reported positive changes after the rehabilitation; however, the group that underwent WBC intervention had greater improvements in the severity of pain, depressive symptoms, disease impact, and quality of sleep. On the contrary, with respect to performance-based physical functioning, we found no significant between-group differences. Our findings suggest that WBC could be a promising add-on treatment to improve key aspects of FM, such as pain, depressive symptoms, disease impact and poor sleep quality.

Ouabain-regulated phosphoproteome reveals molecular mechanisms for Na+, K+-ATPase control of cell adhesion, proliferation, and survival.

The ion pump Na+, K+-ATPase (NKA) is a receptor for the cardiotonic steroid ouabain. Subsaturating concentration of ouabain triggers intracellular calcium oscillations, stimulates cell proliferation and adhesion, and protects from apoptosis. However, it is controversial whether ouabain-bound NKA is considered a signal transducer. To address this question, we performed a global analysis of protein phosphorylation in COS-7 cells, identifying 2580 regulated phosphorylation events on 1242 proteins upon 10- and 20-min treatment with ouabain. Regulated phosphorylated proteins include the inositol triphosphate receptor and stromal interaction molecule, which are essential for initiating calcium oscillations. Hierarchical clustering revealed that ouabain triggers a structured phosphorylation response that occurs in a well-defined, time-dependent manner and affects specific cellular processes, including cell proliferation and cell-cell junctions. We additionally identify regulation of the phosphorylation of several calcium and calmodulin-dependent protein kinases (CAMKs), including 2 sites of CAMK type II-γ (CAMK2G), a protein known to regulate apoptosis. To verify the significance of this result, CAMK2G was knocked down in primary kidney cells. CAMK2G knockdown impaired ouabain-dependent protection from apoptosis upon treatment with high glucose or serum deprivation. In conclusion, we establish NKA as the coordinator of a broad, tightly regulated phosphorylation response in cells and define CAMK2G as a downstream effector of NKA.-Panizza, E., Zhang, L., Fontana, J. M., Hamada, K., Svensson, D., Akkuratov, E. E., Scott, L., Mikoshiba, K., Brismar, H., Lehtiö, J., Aperia, A. Ouabain-regulated phosphoproteome reveals molecular mechanisms for Na+, K+-ATPase control of cell adhesion, proliferation, and survival.

Circadian integration of inflammation and glucocorticoid actions: Implications for the cochlea.

Auditory function has been shown to be influenced by the circadian system. Increasing evidence point towards the regulation of inflammation and glucocorticoid actions by circadian rhythms in the cochlea. Yet, how these three systems (circadian, immune and endocrine) converge to control auditory function remains to be established. Here we review the knowledge on immune and glucocorticoid actions, and how they interact with the circadian and the auditory system, with a particular emphasis on cochlear responses to noise trauma. We propose a multimodal approach to understand the mechanisms of noise-induced hearing loss by integrating the circadian, immune and endocrine systems into the bearings of the cochlea. Considering the well-established positive impact of chronotherapeutic approaches in the treatment of cardiovascular, asthma and cancer, an increased knowledge on the mechanisms where circadian, immune and glucocorticoids meet in the cochlea may improve current treatments against hearing disorders.

Na+-K+-ATPase, a new class of plasma membrane receptors.

The Na(+)-K(+)-ATPase (NKA) differs from most other ion transporters, not only in its capacity to maintain a steep electrochemical gradient across the plasma membrane, but also as a receptor for a family of cardiotonic steroids, to which ouabain belongs. Studies from many groups, performed during the last 15 years, have demonstrated that ouabain, a member of the cardiotonic steroid family, can activate a network of signaling molecules, and that NKA will also serve as a signal transducer that can provide a feedback loop between NKA and the mitochondria. This brief review summarizes the current knowledge and controversies with regard to the understanding of NKA signaling.