The lymphatic system plays a crucial role in maintaining tissue fluid balance, immune surveillance, and the transport of lipids and macromolecules. Lymph is absorbed by initial lymphatics and then driven through lymph nodes and to the blood circulation by the contraction of collecting lymphatic vessels. Intraluminal valves in collecting lymphatic vessels ensure the unidirectional flow of lymph centrally. The lymphatic muscle cells that invest in collecting lymphatic vessels impart energy to propel lymph against hydrostatic pressure gradients and gravity. A variety of mechanical and biochemical stimuli modulate the contractile activity of lymphatic vessels. This review focuses on the recent advances in our understanding of the mechanisms involved in regulating and collecting lymphatic vessel pumping in normal tissues and the association between lymphatic pumping, infection, inflammatory disease states, and lymphedema.

Two major functions of the lymphatic system are the reabsorption of excess interstitial fluid/protein and the coordination of immune cell interactions and trafficking. Specialized junctions between lymphatic endothelial cells optimize reabsorption. The spontaneous contractions of collecting vessels provide active lymph propulsion. One-way valves prevent backflow, and chemokine gradients direct the migration of immune cells. Specialized compartments within the lymph node facilitate antigen-immune cell interactions to produce innate and acquired immunity. Lymphatic injury and/or mutations in genes controlling vessel/valve development result in contractile/valve dysfunction, reduced immune cell trafficking and, ultimately, lymph-edema. Activated CD4+ T cells produce inflammatory mediators that exacerbate these processes, potentially leading to interstitial and lymphatic vessel remodeling and negatively impacting overall function. Mouse models have advanced our knowledge of lymphatic disease, but clinical trials to reduce the impact of inflammatory mediators have yielded mixed success, implying that additional factors underlying human lymphedema are not yet understood.

Background: Microcurrent therapy (MCT) is a novel electrotherapy modality with very low current-levels that may reduce pain especially in joints and muscles.

Aim: The aim of this study is to explore potential effects of MCT on pain in patients with knee osteoarthritis, to explore effects of different treatment parameters and to distinguish them from placebo-effects.

Design: Randomized four arms controlled clinical trial.

Setting: Outpatient tertiary medical care center.

Population: Fifty-six patients with knee OA (Kellgren-Lawrence Score II or III, 14 male and 38 female, mean age: 71.7±7.3 years, pain intensity higher than Numeric Rating Scale [NRS] score 3 from 10).

Methods: Patients were randomized into four groups: MCT with 100 µA (group A), MCT with 25 µA (group B), sham-treatment (group C) and a control-group without intervention. Treatment groups received 10 sessions of MCT for 30 minutes each over a period of 22 days. The primary outcome was daily pain intensity throughout the treatment period measured by a NRS from 0-10. Second outcome measurements were the Knee Osteoarthritis Outcome Score (KOOS), the SF-36 Questionnaire, the Six-Minute Walking Test and the Get-Up-and-Go Test.

Results: Evening pain was reduced significantly in the verum-groups compared to sham group (Group A vs. Group

C: P<0.001, Group B vs. Group

C: P=0.006) and to no intervention (Group A vs. Group

D: P<0.001, Group B vs. Group

D: P=0.002). The difference between sham-therapy and no therapy was not significant. In the pre-post analysis of the KOOS group A improved significantly in the subscale Symptoms. Group A and B and D improved in the Activities of Daily Living subscale.

Conclusions: The results of this RCT suggest that MCT has beneficial effects on pain in patients with knee osteoarthritis that are not explained by a placebo effect. Due to the explorative, pilot character of the study, further confirmation is needed before clear recommendations can be given.

Clinical Rehabilitation Impact: More high-quality RCTs with transparent parameters should be investigated to elucidate potential effects of MCT in the field of physical medicine and rehabilitation. At the present time MCT is a treatment option that could be helpful, in particular for patients who are afraid of unpleasant sensations from electrotherapy with stronger currents.

Microcurrent is a non-invasive and safe electrotherapy applied through a series of sub-sensory electrical currents (less than 1 mA), which are of a similar magnitude to the currents generated endogenously by the human body. This review focuses on examining the physiological mechanisms mediating the effects of microcurrent when combined with different exercise modalities (e.g. endurance and strength) in healthy physically active individuals. The reviewed literature suggests the following candidate mechanisms could be involved in enhancing the effects of exercise when combined with microcurrent: (i) increased adenosine triphosphate resynthesis, (ii) maintenance of intercellular calcium homeostasis that in turn optimises exercise-induced structural and morphological adaptations, (iii) eliciting a hormone-like effect, which increases catecholamine secretion that in turn enhances exercise-induced lipolysis and (iv) enhanced muscle protein synthesis. In healthy individuals, despite a lack of standardisation on how microcurrent is combined with exercise (e.g. whether the microcurrent is pulsed or continuous), there is evidence concerning its effects in promoting body fat reduction, skeletal muscle remodelling and growth as well as attenuating delayed-onset muscle soreness. The greatest hindrance to understanding the combined effects of microcurrent and exercise is the variability of the implemented protocols, which adds further challenges to identifying the mechanisms, optimal patterns of current(s) and methodology of application. Future studies should standardise microcurrent protocols by accurately describing the used current [e.g. intensity (μA), frequency (Hz), application time (minutes) and treatment duration (e.g. weeks)] for specific exercise outcomes, e.g. strength and power, endurance, and gaining muscle mass or reducing body fat.

The lymphatic system in skin plays important roles in drainage of wastes and in the afferent phase of immune response. We previously showed that activation of vascular endothelial growth factor receptor (VEGFR), specifically the VEGFC/VEGFR-3 pathway, attenuates oedema and inflammation by promoting lymphangiogenesis, suggesting a protective role of lymphatic vessels against skin inflammation. However, it remains unknown how physical stimuli promote lymphatic function. Here, we show that lymphatic endothelial cells (LECs) are activated by direct-current (DC) electrical stimulation, which induced extension of actin filaments of LECs, increased calcium influx into LECs, and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK). An inhibitor of focal adhesion kinase, which plays a role in cellular adhesion and motility, diminished the DC-induced extension of F-actin and abrogated p38 phosphorylation. Time-lapse imaging revealed that pulsed-DC stimulation promoted proliferation and migration of LECs. Overall, these results indicate that electro-stimulation activates lymphatic function by activating p38 MAPK.

Objective: The primary aim is to assess the efficacy of microcurrent, a form of electrical stimulation, as an adjunct therapy in accelerating healing in chronic wounds by reducing wound size and pain level. The secondary aim is to assess the qualitative changes in these parameters: inflammatory symptoms, vasodilation, sleep quality, gait and frequency of bowel movement.

Method: Eligible patients with chronic wounds were enrolled between March and June 2016, from the Wound Care Unit, Hospital Kuala Lumpur in this consecutive case series. Standard wound care was performed with microcurrent as an adjunct therapy. Each patient was treated with an anti-inflammatory frequency, followed by a vasodilation frequency, while having their wounds cleansed during each dressing change. Patients were loaned a home-microcurrent device to treat themselves three times daily using a tissue repair frequency for four weeks.

Results: A total of 100 patients with chronic wounds, such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers, were recruited. During the four-week treatment period, all patients had a reduction in wound size, with 16 having complete wound closure. All 89 of the 100 patients who complained of pain, associated with their wound, experienced reduced pain scores, with 11 being pain-free at the end of the four-week period. There was significant reduction (p<0.001) in both mean pain score and mean wound area during the treatment period, as well as improvements in other parameters, such as reduction in inflammatory symptoms (leg swelling, foot stiffness), increased vasodilation (skin discolouration, leg heaviness, early morning erection, sensation), improvement in sleep quality, gait, and frequency of bowel movement. No adverse events were reported.

Conclusion: The results of this study show there was significant reduction in wound area and pain score during the treatment period. The ease of use of microcurrent devices would advocate its use in accelerating wound healing.

Aims: To analyse the effects of microcurrent on L929 fibroblast cell culture.

Methods: Cells were cultivated in six-well plates at densities of 5×10, 1×10, 3×10 and 5×10 cells/well to determine the best plating density. Subsequently, two methods of current application were tested: with a paper cone coupled to the electrode (M1) and with the electrode directly inside the well (M2). Then, streams of 60µA (G60), 100µA (G100), 500µA (G500) and 900µA (G900) were applied to the cells (n=3) once a day for three minutes, for a period of one (T1), two (T2) and three days (T3). The MTT assay method was used to evaluate cell proliferation. For the quantification of the inflammatory markers by flow cytometry, the group and time that presented the best results were selected.

Results: The ideal plating density was established as 1x10 cells/well and M2 as the best application method. An increase in cell viability was observed at all intensities from T1 to T2, but with no significant differences. From T2 to T3, there was a decrease in viability in all groups, with a significant difference only in G500 (p<0.05). Flow cytometry was performed in the GC and G900 groups at T2. It was possible to observe an increase of 0.56pg/ml in Interleukin (IL)-17 and a decrease of 5.45pg/ml in IL-2.

Conclusion: This study showed that two applications of microcurrent increases cell proliferation and modulates the inflammatory response, aiding tissue regeneration and playing a key role in rehabilitation.