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Acti patch relieves delayed onset muscle soreness


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Acti patch relieves delayed onset muscle soreness

  1. 1. 1 Pulsed electromagnetic field therapy reduces delayed onset muscle soreness in marathon runners. A double-blind randomized placebo- controlled study. 1 Christina Haugaard Rasmussen, 1 Michael Skovdal Rathleff, 1 Camilla Rams Knudsen, 1 Søren Thorgaard Skou, 2 Martin Grønbech Jørgensen, 3 Jens Lykkegaard Olesen, 1 Vesal Khalid, 1 Sten Rasmussen Affiliations: 1: Orthopeadic Surgery Research Unit, Aalborg Hospital - Aarhus University Hospital, Denmark 2: Department of Geriatrics, Aalborg Hospital - Aarhus University Hospital, Denmark 3: Department of Rheumatology, Aalborg Hospital – Aarhus University Hospital, Denmark Corresponding author: Sten Rasmussen Associate Professor Director of Research + 45 99 32 23 67 + 45 25 52 04 62 (mobile) AARHUS UNIVERSITY HOSPITAL - AALBORG HOSPITAL Orthopaedic Surgery Research Unit Research and Innovation Center 15 Soendre Skovvej DK-9000 Aalborg Keywords: pain, delayed onset muscle soreness, pulsed electromagnetic field, marathon 18 pages 5 tables (2 demography, daily running, AUC, Vas scores) and 2 figures (Flow diagram, Vas scores)
  2. 2. 2 Abstract (150 ord ud af 250 tilladte) Objective: To investigate the efficacy of pulsed electromagnetic fields (PEMF) in reducing delayed onset muscle soreness (DOMS) in marathon runners. Design: Double-blind, randomized, placebo-controlled trial Methods: 133 marathon runners aged 18 or above were randomly assigned to either PEMF or a placebo device. Both the active group (n=69) and the placebo group (n=64) were instructed to use the device 20 minutes per session, four times a day in the five days after a completed marathon. Primary treatment outcome was pain assessed by visual analog scale (VAS) during a 90° squat three times a day in the five days after the completed marathon. These VAS scores were then described with area under curve (AUC). Results: Subjects randomized to active treatment had significantly lower pain than the placebo group with AUC 568 (IQR: 192-1198) and 848 (IQR: 478-2220), p=0.024. (p = 0.024). Conclusion: PEMF reduced DOMS in runners completing a marathon run. Nyt Abstract: Pulsed Electromagnetic Field Therapy (PEMF) is a bioelectromagnetics that induces small electrical currents and has been shown to reduce pain in different indications. However inconsistencies exist and not all studies are conclusive. Delayed onset muscle soreness (DOMS) is a frequent phenomenon seen in marathon runners and is a defined acute sensation of pain and discomfort after strenuous exercise. The objective of this double blind randomized trial was to investigate the efficacy of PEMF in reducing DOMS in marathon runners. A total of 133 marathon runners aged 18 or above were randomly assigned to either PEMF or a placebo device. Both the active group (n=69) and the placebo group (n=64) were instructed to use the device 20 minutes per session, four times a day in the five days after a completed marathon. Primary treatment outcome was pain assessed by visual analog scale (VAS) during a 90° squat three times a day in the five days after the completed marathon. These VAS scores were then described with area under curve (AUC).Subjects randomized to active treatment had significantly lower pain than the placebo group with AUC 568 (IQR: 192-1198) and 848 (IQR: 478-2220), p=0.024. (p = 0.024). PEMF reduces DOMS in runners completing a marathon run.
  3. 3. 3 1. Introduction ( 309 (med overskrifter) ud af 500 tilladte) Pulsed Electromagnetic Field Therapy (PEMF) belongs to the field of bioelectromagnetics. It differs from other bio magnetics because it emits a sub threshold, low-power, low-frequency electromagnetic waveform (1). The PEMF devices induce small electrical Faraday currents in the tissue because of a constant changing magnetic flux (2). There is a growing body of clinical evidence that PEMF have analgesic effects on humans. PEMF has also been shown to reduce pain in patients with osteoarthritis (3,4), rheumatoid arthritis (5,6), diabetic neuropathy (7), fibromyalgia (1,8), distal radius fractures (9), pelvic pain (10) and postoperative pain (11-13). However inconsistencies exist and not all studies find a positive effect on pain reduction (2,3,14-16) and some are inconclusive (17,18). However no one has yet investigated the effect of PEMF on post exercise delayed onset muscle soreness (DOMS). Delayed onset muscle soreness (DOMS) is a frequent phenomenon seen in marathon runners in the days after completing a marathon run (19-21). Completing a marathon results in a significant load on the human body. Physiologic effects of a marathon involves muscular and connective tissue damage which initiates an inflammatory response as well as release of metabolic factors like lactate and free radicals, intracellular metabolites and by- products of proteolysisThese are effects proposed to explain DOMS(20,21). DOMS is defined as the sensation of pain and discomfort in skeletal muscles that occurs after eccentric muscle actions or strenuous exercise. The soreness increases in intensity in the first 24 to 72 hours after the exercise and remains for up to 5 days. (22-24). DOMS may delay a speedy return to normal daily living and normal weekly running mileage why a reduction of DOMS are warranted. The objective of this study is to investigate the efficacy of pulsed electromagnetic field compared with placebo in reducing DOMS in runners completing a marathon. We hypothesized that PEMF will reduce DOMS in marathon runners. 2. Methods 2.1 Description of the studied volunteers Subjects were recruited from three marathons in the summer of 2011; Aabenraa Bjergmarathon, Randers Flodmarathon and Rold Skov Marathon. Eligibility criteria were age 18 years or more, completed the marathon and able to speak and read Danish. We emailed the 439 subjects prior to the marathon to tell them about the project and that we would contact them at the finish line if they completed the marathon. A total of 94 did not complete the marathon and 212 declined to participate. At baseline were 133 subjects (114 men and 19 women) were included. The questionnaire was not returned by 39 subjects and therefore 94 subjects were left for the final data analysis (70,7%) (Figure 1). Baseline characteristics of participants indicated no differences between the two randomized groups. Characteristics of the 39 participants lost to follow-up were similar to those completing the study (Table 1) 2.2 Intervention One group received two active PEMF devices and the other group received two sham devices. The subjects were asked to attach one device to the most painful area on each thigh and activate the devices 20 minutes four times a day in the five days following the marathon. The pulsed electromagnetic field signal was delivered from a small (2,5 cm diameter, 1 cm thick) battery-powered generator to a single-turn 12-cm-diameter electrical coil. Inside of the circle and several cms outside the circle a fairly uniform magnetic field of the order 0.1 µTesla normal to the plane of the loop was established, generated by a current of the order 6 mA. The magnetic field in turn generates an electric field of the order 1 V/m rotationally symmetric around the axis of the loop. Both fields
  4. 4. 4 are largest near the loop, the electric field being zero on the axis (Figure 2).. The device emitted 0.1 ms wide rectangular bursts with a repetition rate of 1 kHz, and a carrier frequency of 27 MHz. Peak magnetic field intensity had an effect of 7.3 mW/cm 3 . 2.3 Outcome measurements The observation period was 5 days starting the first day following the marathon. Self-report questionnaires were given to all subjects after inclusion. The subjects were told to return the questionnaires in provided post-marked envelopes. Primary outcome measure was thigh muscle pain measured on a 10 cm visual analog scale during a 90° squat three times a day; when they woke up, at 12 pm and 8 pm. On the VAS the subjects were asked to draw a line somewhere between the left extreme (no pain) and the right extreme (worst possible pain). VAS has well accepted clinimetric properties and has been used to measure DOMS (25-29). On the day of inclusion height, weight, age, BMI, gender, marathon result and current injuries were recorded. In the self-report questionnaire subjects were asked about daily activity (minutes); use of PEMF (minutes); use of pain killers (yes/no). On the fifth day, subjects were asked if they thought they received an active (yes/no/do not know) . On the sixth day following the marathon all subjects received a mail to thank them for participation and to remind them to return of the questionnaire. If the questionnaire was not received within one week of this date, participants were emailed again and telephoned and asked to mail it as quickly as possible. If participant did not send as agreed, they were once again emailed and called to remind them to send back the questionnaire. Study participant was told to contact the responsible investigator if they felt side effect that could be attributed to the use of PEMF. 2.4 Sample size, ethics, randomization and statistical analysis A pilot study was conducted before the current trial. Based on data from the pilot study we needed 116 runners to detect a difference of 15mm on a VAS using a standard deviation of 25mm and 90 % power at a 5 % significance level. Written informed consent was obtained from all participants prior to enrolment. The study was approved by the local ethics committee (N-20100021), and the Danish Data Protection Agency (2008-58-0028). The study was registered in Clin Trial Gov () All runners were contacted at the finish line of the marathon and asked to participate in the study. After inclusion and written informed consent the runners were randomly allocated into receiving device A or device B. A six block randomization procedure stratified into gender was used. The design was a double blind randomized placebo- controlled trial. A person not involved in the study prepared two batches of PEMF-devices (ActiPatch TM , Bioelectronic). One batch was marked as A and one was marked as B. Only this person was aware of which batch contained active devices. All personnel in the study and participants remained blinded until all possible self-report questionnaires had been returned. The sham devices did not differ from the active devices in shape, color or weight. Neither the active nor the sham devices caused any sensations. To assess if blinding of participants was successful all participant was asked to state in the questionnaire which group they thought they were assigned to. Data were analyzed with a per protocol analysis. Intention to treat analysis were not possible since only participants who completed the entire clinical trial and sent back the questionnaire provided VAS score data to analyses. All analyses were done using Stata Version 11 and p-values of less than 0.05 were considered significant. Parametric data was analyzed with un-paired Student t-test and non-parametric data with Fisher’s exact test and Wilcoxon rank-sum test. Primary outcome was described with the area under a curve (AUC). This area was calculated by addition of two
  5. 5. 5 consecutive vas scores divided by the time interval between the two VAS scores. This was done with all 15 VAS scores for each single participant and addition of the fractions resulted in the AUC. Bang's and James' indexes was used to asses the success of blinding. 3. Results 3.1. Outcome The between group difference for the primary outcome of thigh pain during semi-squat during 5 days following the marathon showed a significantly lower pain among the group receiving an active device compared to the placebo group AUC 568 (IQR: 192-1198) and 848 (IQR: 478-2220), p=0.024). The secondary outcome showed that the group receiving active PEMF ran for a significantly longer time on the first day following the marathon (running time 61 min vs. 27 min, p=0.017), table X. 3.2 Adherence, adverse events and cointerventions. The mean duration of daily PEMF use during the 5 days following the marathon was 360 minutes in the placebo group and 320 minutes in the active group (p=0.66). No adverse effects of the PEMF-device were reported during the study. Use of analgesics was reported by 3/69 in the sham group and 0/64 in the active group. 3.3 Drop out analysis No significant differences were found between drop outs and the participants who completed the study in terms of age, gender and marathon time. 3.4 Blinding analysis A blinding index was calculated from outcome about whether the subjects believed they had received an active device, a placebo device or did not know. James’ method showed a successful blinding (p=0.997) whereas Bang’s method showed a successful blinding in the active treated group (p=1.00) and an unsuccessful blinding in the placebo treated group (p=0.00001) 4. Discussion (2064 ud af 1500 tilladte) nu 1499 ord The results from this double-blind, randomized, placebo-controlled study, demonstrated that PEMF had a significant effect on reducing DOMS in marathon runners compared to placebo. Furthermore there was a strong trend towards subjects receiving the active PEMF-device were more active in the days following the marathon race This is the first study that has found a positive pain reducing effect of PEMF on DOMS. Earlier research has indicated a strong analgesic effect of PEMF working through the inflammatory processes, opioid pathways, change in neural and brain activity and impact on membrane potentials, ion exchange and permeability of cells. Two double-blind, placebo- controlled, randomized studies found up to 300 percent decrease in pain scores in postoperative breast reduction patients (12,13). The analgesia was suggested to result from an effect of PEMF on inflammation. Rohde et al. did not find significant differences for TNF-α, VEGF and FGF-2, but demonstrated that IL-1β levels in the wound exudates of actively treated patients were significantly reduced. Another study showed disruption of IL-1 signaling reduced wound fibrosis and scar formation, improved skin architecture and increased tensile strength (32). The results of these studies showed that PEMF reduced pain and furthermore that PEMF’s reduction of IL-1 both reduced inflammation and improved tissue regeneration. Shupak et al suggested that pain reducing effect of PEMF acted through an opioid pathway. First they demonstrated an analgesic effect of PEMF on mice that were later replicated in a study on humans (33,34). Their work suggested
  6. 6. 6 that PEMF did not affect the human perception in general, but increased pain thresholds indicative of an analgesic response (34). Their work was further supported by other studies which showed that the use of PEMF changed opioid receptor densities in the brain (35) and that the PEMF effect was mediated by endogenous opioids in the central nervous system (36,37). The attenuation of PEMF induced analgesia by the opioid antagonist naloxone as well as other opioid receptor antagonists supported these arguments (38,39). A PEMF study on snails found PEMF to increase enkephalinase inhibitor and induce opioid analgesia (38). These findings suggested the analgesic effects of PEMF somehow involved an augmentation of endogenous opioids (1). Some studies have shown that helmets with PEMF can change brain wave activity, suggesting that the effects of PEMF are the result of a direct effect on central nervous function (1) Robertson et al. found significant correlations between the changes in neural activation and field strength for both the anterior cingulated cortex and insula, which are brain areas involved in pain perception. Increased PEMF strength exposure induces less post-exposure processing of pain indicating a dose-dependent effect (40). Ryczko et al. suggest PEMF influence the firing patterns of thalamic neurons to cause analgesia (41). One of the most popular explanations to explicate the positive effect of electromagnetic fields on the body is their influence on the membrane potential of body cells. Canapp et al. suggested damaged or diseased cells have an altered cellular resting membrane potential, which in turn alters the cellular ion exchange and oxygen utilization of the cell. Altered oxygen utilization has been found in delayed healing tissues and arthritic joints. PEMF stabilized the membrane potential and improved ion exchange and therefore oxygen utilization according to this article (42). Bachl et al. have made calculations and do not think it is realistic to affect the membrane potential with a weak electromagnetic intervention. They think it is more likely that electromagnetic fields interfere with the Ca 2+ signaling pathway of cells (43). It has also been suggested, but still not proven that PEMF reduces the permeability of cell membranes and therefore the number of action potentials (2). Since muscular and connective tissue inflammation is a consequence of a marathon and results in DOMS the analgesic effect of PEMF working through the inflammatory processes is very plausible to this study. Further PEMF working on membrane potentials, ion exchange or permeability of cells are all local mechanisms which may be the reason to the less inflammation at the PEMF site and thus involved in the analgesia of this study. DOMS was measured on a self-reported pain VAS. Other methods to measure pain are pain threshold assessment and neurophysiological assessment. These methods would not be feasible on a large scale basis 5 days following the marathon. VAS is a standard tool in clinical trials to assess the efficacy of analgesic treatments. VAS allows a maximum sensitivity and comparisons of pain intensities and between-patient scores. It also eliminates the potential bias arising from memorization of responses given on previous questionnaires, which is often the case with descriptive scales. The only other study found to investigate the effects of PEMF after physical exercise was a double-blind, randomized, placebo-controlled study carried out in a laboratory(31). In resemblance with our results they found an accelerated recovery after physical strain compared to placebo treatment. The physical exercise was a 4 min step test followed by a 20 min treament with either PEMF or placebo. The PEMF treatment resulted in a more rapid return of the heart rate to the initial state. They also found that subjects were not able to feel when PEMF was applied as PEMF had no effect on general feeling of well-being. Likewise a large percentage in both groups thought they had received placebo as they were not able to feel the current induced by the PEMF device. Most likely this is also the reason why the blinding appeared unsuccessful in placebo group of this study. PEMF provides a noninvasive, safe and easy method to treat the site of pain and inflammation and a variety of diseases and pathologies. Many studies show PEMF is useful in treatment of the musculoskeletal system as well as for pain relief. Furthermore PEMF is not systemic and not governed by pharmacokinetics. PEMF appears instantaneously in all compartments of the target tissue where endogenous anti-inflammatory and subsequent tissue repair processes
  7. 7. 7 can be modulated (12). Therefore PEMF may accelerate tissue regeneration reduce DOMS and counteract the strong physiological strain of the marathon. However PEMF could also induce a negative long term effect since PEMF modulates DOMS and gives the runners the possibility of a speedy return to weekly mileage. One might hypothesize that PEMF counteracts the human body`s normal response to a marathon run and this could lead to overuse injuries since the runner is not aware of the body`s normal pain response and continue running when he should be resting.Though skeletal muscles have a remarkable ability for regeneration and chronic effects of overuse can therefore probably be ignored {{102 Appell,H.J. 1992}}. The only major contraindications of PEMF are active hemorrhage and electrical implants. Pregnant patients should also avoid PEMF due to the lack of data (42). Finally it need to be emphasized that there were no reported side effects with the use of PEMF in either our or any of the above-mentioned trials (43,46). The strengths of this study were the rigorous study design and blinding of all personnel and participants. Furthermore we enrolled a high number of subjects from three yearly marathons. The marathons were not a set up for our study and the situation with DOMS following a marathon reflects reality. One of the primary weaknesses were the necessity of making a per protocol analysis instead of a intention to treat analysis. In addition the completion rate was lower than expected with a drop out rate of 29,3 %. We do not know how the drop outs would have affected our study if they had completed, but our drop out analysis does not show any differences between the subjects who completed and the subjects who dropped out. One of the main reasons for the high percentage of dropout could be that some of the runners did not have enough pain to find the motivation to complete the self-report questionnaires. These drop outs might be experienced marathon runners, ultra runners and the runners with fast marathon times since training attenuates pain {{123 Schwane,J.A. 1987}}. To avoid these drop outs we could have made thresholds for pain, marathon time and number of marathons as inclusion criteria. This experiment was conducted with PEMF intensity and pulse rate defined by the manufacturer. There is a possibility that other intensities and pulse rates could have changed the effects (30). There are only a few data available that discuss the choice of parameters. These data suggest a “window of response” exists within a specific PEMF setting, and the effect outside this range is negligent. Robertson et al. found increases or decreases in nociceptive sensitivity with different magnetic field exposure which argue for a specific “window of reponse”(40). This could explain the apparently conflicting findings in previous studies using different exposure profiles. Double-blind, randomized, placebo-controlled studies using a variety of PEMF exposure protocols are necessary to reach any conclusions regarding the potential benefits of PEMF in treatment of pain and to achieve the optimal values of parameters of magnetic fields. Future research should investigate the effect of PEMF on musculoskeletal disorders where accelerated tissue regeneration and pain relief is needed. Conclusion This double-blind, randomized, placebo-controlled study shows that active PEMF reduce DOMS in runners completing a marathon. This finding may lead to a quicker recovery after strenuous exercise.
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