Phantom pain reduction by low-frequency and low-intensity electromagnetic fields

Although various treatments have been presented for phantom pain, there is little proof supporting the benefits of pharmacological treatments, surgery or interventional techniques, electroconvulsive therapy, electrical nerve stimulation, far infrared ray therapy, psychological therapies, etc. Here, we report the preliminary results for phantom pain reduction by low-frequency and intensity electromagnetic fields under clinical circumstances. Our method is called as Electromagnetic-Own-Signal-Treatment (EMOST). Fifteen people with phantom limb pain participated. The patients were treated using a pre-programmed, six sessions. Pain intensity was quantified upon admission using a 0-10 verbal numerical rating scale. Most of the patients (n?=?10) reported a marked reduction in the intensity of phantom limb pain. Several patients also reported about improvement in their sleep and mood quality, or a reduction in the frequency of phantom pain after the treatments. No improvements in the reduction of phantom limb pain or sleep and mood improvement were reported in the control group (n?=?5). Our nonlinear electromagnetic EMOST method may be a possible therapeutic application in the reduction of phantom limb pain. Here, we also suggest that some of the possible effects of the EMOST may be achieved via the redox balance of the body and redox-related neural plasticity.     

Phantom pain reduction by low-frequency and low-intensity electromagnetic fields

Although various treatments have been presented for phantom pain, there is little proof supporting the benefits of pharmacological treatments, surgery or interventional techniques, electroconvulsive therapy, electrical nerve stimulation, far infrared ray therapy, psychological therapies, etc. Here, we report the preliminary results for phantom pain reduction by low-frequency and intensity electromagnetic fields under clinical circumstances. Our method is called as Electromagnetic-Own-Signal-Treatment (EMOST). Fifteen people with phantom limb pain participated. The patients were treated using a pre-programmed, six sessions. Pain intensity was quantified upon admission using a 0–10 verbal numerical rating scale. Most of the patients (n = 10) reported a marked reduction in the intensity of phantom limb pain. Several patients also reported about improvement in their sleep and mood quality, or a reduction in the frequency of phantom pain after the treatments. No improvements in the reduction of phantom limb pain or sleep and mood improvement were reported in the control group (n = 5). Our nonlinear electromagnetic EMOST method may be a possible therapeutic application in the reduction of phantom limb pain. Here, we also suggest that some of the possible effects of the EMOST may be achieved via the redox balance of the body and redox-related neural plasticity.     

A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

A_2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A_2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A_2AAR stimulation in a rat model of arthritis. We investigated A_2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A_2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A_2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A_2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A_2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A_2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A_2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A_2AARs in lymphocytes from RA patients. The effectiveness of A_2AAR stimulation in a rat model of arthritis supported the role of A_2AAR agonists as potential pharmacological treatment for RA.     

Effects of cyclotronic ion resonance on human metabolic processes: a clinical trial and one case report

We studied the effects of ion cyclotron resonance (Seqex) magnetic therapy on the blood of thirty two healthy volunteers. They received 15 treatments each 27 minutes in length, distributed over 5 weeks. The concentrations of two blood components, malondialdehyde (MDA) and cholesterol were measured in each subject, immediately before and immediately after the 15 treatments as well as one month after the final treatment. Highly significant reductions in MDA concentrations, averaging 53.8% were noted just after the 15 treatments, tending to return to the original concentrations one month later. The effect on HDL and LDL cholesterol levels were not significant. The implication of this work is that this type of therapy may be useful in dealing with oxidative stress.     

Utilization of extremely low frequency (ELF) magnetic fields in chronic disease; five years experience: three case reports

We present three examples of the use of ELF magnetic therapy, two cases of multiple sclerosis and one of chronic pulmonary disease. In each of the two MS cases the Seqex device was applied as an adjunct to antioxidant medication two times a week for six weeks. Radiological and MRI examination indicated improvement in the two MS patients and stabilization in the patient with obstructive pulmonary disease following merely five treatments.     

Excitability changes in the sciatic nerve and triceps surae muscle after spinal cord injury in mice

Background

Ischemia reperfusion (I/R) is common in various pathological conditions like diabetic complication, rheumatic arthritis, necrotizing vascular occlusive disease and trauma.

Methods

We have evaluated the effect of tacrolimus (1, 2 and 3 mg/kg, p.o. for 10 consecutive days) on femoral arterial ischemic reperfusion (I/R) induced neuropathic pain in rats. Behavioral parameters (i.e. hot plate, radiant heat, acetone drop, tail heat hyperalgesia, tail flick and tail cold allodynia tests) were assessed at different time intervals (i.e. 0, 1, 4, 7, 10, 13 and 16^th day) and biochemical analysis in serum and tissue samples were also performed along with histopathological studies.

Results

Behavioral pain assessment revealed increase in the paw and tail withdrawal threshold in tacrolimus treated groups against hyperalgesic and allodynic stimuli as compared to the sham control group. We observed a decrease in the serum nitrate and thiobarbituric acid reactive substance (TBARS) levels along with reduction in tissue myeloperoxidase (MPO) and total calcium levels, whereas, rise in tissue reduced glutathione levels in tacrolimus treated groups. However, significant results were obtained in medium and high dose treated group as compared to sham control group. Histopathological study had revealed the increase in the neuronal edema and axonal degeneration in the I/R group whereas, tacrolimus ameliorate these effects.

Conclusion

Our results indicate the anti-oxidative, anti-inflammatory and calcium modulatory actions of tacrolimus. Therefore, it can be used as a therapeutic agent for the treatment of vascular inflammatory related neuropathic pain.     

SOME RECENT ADVANCES IN THE SYMPTOMATIC TREATMENT OF OSTEOARTHRITIS

In over 400 treatments with procaine intravenously, moderate to good improvement was noted in about 60 per cent of patients with osteoarthritis and radiculitis. Definite improvement after a single treatment was noted occasionally, but more often relief was not obtained until six to eight treatments had been given. Symptoms due to osteoarthritic changes in peripheral joints did not respond as well as did those due to spinal arthritis.Curare relieves some of the pain of arthritis due to muscle spasm, but does not bring improvement in motion of the small joints, such as those of the fingers.Preliminary experience with a new synthetic drug, 3-ortho-toloxy-1, 2-propanediol (Tolserol®), which produces muscular relaxation differing from that induced by curare, suggests further clinical trial.Intra-articular acidification by injection relieved pain in about 50 per cent of patients with osteoarthritis of the knee.     

Substance P and Acute Pain in Patients Undergoing Orthopedic Surgery

Objective

There is a limited information about the role of Substance P (SP) in acute pain nociception following surgical stimulation in patients with a chronic inflammatory state not to mention the link between this neuropeptide level changes and intensity of pain. The goal of the research was to find the correlation between SP level changes and acute pain intensity in patients with rheumatoid arthritis undergoing elective orthopedic surgery.

Material and Methods

Patients with rheumatoid arthritis (RA) were enrolled in the study. The correlation between acute pain intensity and concentration of SP in serum as well as in drainage fluid from postoperative wound was assessed in patients with RA who underwent Total Knee Replacement (TKA) under spinal anesthesia.

Results

In patients with RA a correlation between intensity of acute pain and serum SP was found postoperatively, whereas there was no correlation between intensity of acute pain and concentration of SP in drainage fluid.

Conclusions

1. The correlation between acute pain intensity and SP serum concentration was found postoperatively in patients with RA. 2. The correlation between acute pain intensity and SP concentration in drainage fluid was not found postoperatively in patients with RA.     

The autistic syndrome and endogenous ion cyclotron resonance: state of the art

The autistic syndrome is a multigenic disease whose expression is different according to the level of involvement of different structures in the central nervous system. The pathogenesis is unknown. No completely effective medical therapy has yet been demonstrated. Accepting the request of the families of eight autistic children in Lomazzo, Milan and Naples, we used ion cyclotron resonance (Seqex therapy) therapeutic support after many other therapies had been already carried out on these patients. After regimens consisting of 20-30 treatments with ICR, improvements were noted in all cases.     

Risk factors for bone loss in patients with rheumatoid arthritis treated with biologic disease-modifying anti-rheumatic drugs

Objective

Osteoporosis is a complication of rheumatoid arthritis. We examined the risk factors for bone loss in rheumatoid arthritis patients receiving biological disease-modifying anti-rheumatic drugs. Lumbar spine and femoral neck bone mineral density was measured at two time points in 153 patients with rheumatoid arthritis managed with biological disease-modifying anti-rheumatic drugs. We examined patients’ variables to identify risk factors for least significant reduction of bone mineral density.

Results

Least significant reduction of lumbar spine bone mineral density (≤ ? 2.4%) was seen in 13.1% of patients. Least significant reduction of femoral neck bone mineral density (≤ ? 1.9%) was seen in 34.0% of patients. Multiple logistic regression analysis showed that a risk factor for least significant reduction of the lumbar spine was high-dose methylprednisolone use. Multiple regression analysis showed that a risk factor for least significant reduction of the femoral neck was short disease duration. Our findings showed that a risk factor for femoral neck bone mineral density reduction was a short disease duration. These findings suggest that rheumatoid arthritis patients receiving treatment with biological disease-modifying anti-rheumatic drugs may benefit from earlier osteoporosis treatments to prevent femoral neck bone loss.

     

Comparison between penicillamine and sulphasalazine in rheumatoid arthritis: Leeds-Birmingham trial.

Sulphasalazine was first formulated by Svartz in the early 1940s, specifically for use as a remission inducing drug in rheumatoid arthritis. After the publication of an unfavourable trial, however, the drug was restricted to patients with ulcerative colitis. In the late 1970s sulphasalazine was re-examined in rheumatoid arthritis and favourable results reported in "open" trials. A double blind controlled trial was therefore conducted comparing enteric coated sulphasalazine and D-penicillamine in patients with active rheumatoid arthritis. A total of 63 patients were recruited in two centres; 31 were treated with sulphasalazine and 32 received penicillamine. After 16 weeks'' treatment both drugs had produced significant improvements in clinical score, pain score measured on a visual analogue scale, grip strength, Ritchie articular index, erythrocyte sedimentation rate, and serum C reactive protein concentration. Nausea was the major side effect in the sulphasalazine treated group. No potentially dangerous effects of sulphasalazine were encountered in contrast with those seen in the penicillamine group. The results suggest that sulphasalazine is an effective and safe drug capable of producing remissions in active rheumatoid arthritis. They also lend confidence to the use of preliminary "open" trials as a means of screening for remission inducing drugs in rheumatoid arthritis.     

A cetylated fatty acid topical cream with menthol reduces pain and improves functional performance in individuals with arthritis

This investigation was an extension of a previous study conducted in our laboratory in which we showed that 1 month of treatment with a topical cream (Celadrin) consisting of cetylated fatty acids was effective for reducing pain and improving functional performance in individuals with osteoarthritis (OA) of the knee (Kraemer et al., Journal of Rheumatology, 2004). We wanted to verify that the addition of menthol to the compound would produce a similar percentage of improvement in therapeutic effects. We used a single treatment group with a pre-post experimental design to examine % treatment changes. Individuals diagnosed with OA of the knee (N = 10; age, 66.4 +/- 11.5 years) and severe pain (e.g., OA, rheumatoid arthritis) of the elbow (N = 8; age, 59.1 +/- 18.2 years) and wrist (N = 10; age, 60.3 +/- 16.8 years) were tested for pain and functional performance before and after 1 week of treatment with a topical cream consisting of cetylated fatty acids and menthol applied twice per day. In individuals with knee OA, significant improvements in stair-climbing ability (about 12%), "up-and-go" performance (about 12%), balance and strength (about 16.5%), and range of motion (about 3.5%) were observed, as were reductions in pain. In individuals with severe pain of the elbow and wrist, significant improvements in dynamic (about 22 and 24.5%, respectively) and isometric (about 33 and 42%, respectively) local muscular endurance were observed, as was a reduction in pain. Neither group demonstrated significant changes in maximal grip strength or maximal force production. One week of treatment with a topical cream consisting of cetylated fatty acids and menthol was similarly effective for reducing pain and improving functional performance in individuals with arthritis of the knee, elbow, and wrist. The % changes were consistent with our prior work on the compound without menthol. Further work is needed to determine the impact of menthol in such a cream. Nevertheless, our data support the use of a topical cream consisting of cetylated fatty acids (with or without menthol) for enhancing the potential for exercise training in this population.     

Rheumatoid arthritis: A study of relaxation and temperature biofeedback training as an adjunctive therapy

Rheumatoid arthritis (RA) is a painful systemic disease and is believed to be exacerbated by stress. Relaxation and biofeedback strategies have demonstrated utility in alleviating both pain and stress-related symptomatology, and therefore were tested for efficacy with this disease in a two-phase study. First, 24 patients were taught a relaxation technique and then trained in either temperature elevation or reduction. Second, a group of 15 patients thus trained was compared with 8 others who received traditional physiotherapy modalities. Psychological tests, functional/physical evaluations, as well as measurements related to pain, sleep, and other activities were carried out. Results of the first study revealed significant and positive changes following treatment that were primarily related to pain, tension, and sleep patterns for both groups, but no differential effects were noted between temperature elevation or reduction conditions. This was attributed to both groups having maintained temperature above baseline during biofeedback training. The results of the second study consistently favored the relaxation and biofeedback over the physiotherapy group on the physical/functional indices. The psychological measures tended to remain constant throughout both studies, leading to the conclusion that the effectiveness of treatment was specific to physical functioning rather than to a psychological enhancement of well-being.This work was conducted in partial fulfillment of the doctoral requirements at North Texas State University by Phillip McGraw. This work was also performed pursuant to Institutional Grant No. 5-S07-RR05426-12 and NIAMDD No. 5 P60 AM20628-02.     

Potential economic impact of using a proprietary willow bark extract in outpatient treatment of low back pain:An open non-randomized study

An open, non-randomised, study (postmarketing surveillance) was carried out on three groups of patients aged 18 to 80 presenting over an 18 month period with acute exacerbations of low back pain. The objective was to assess the possible economic impact of including a regular dose of proprietary willow bark extract (Assalix) in the treatment provided. A first group of 115 patients, presenting to 3 general practitioners in the first 3 months, was prescribed a daily dose of extract containing 120 mg of salicin (group W120). They also had access, if necessary, to the range of conventional treatments allowed for in the general practitioners' budgets. A second group of 112 patients presenting to the same general practitioners over the next 15 months, was prescribed extract equivalent to 240 mg salicin per day (group W240). A third "control" or "comparator" group of 224 patients, presenting to 3 orthopedists (specialists in physical medicine) over the whole 18 month period, received only the conventional therapeutic options allowed in the orthopedists' budgets (Group C). In the group C patients, the exacerbations had been shorter but the pain had been more intense as judged by Arhus Index and Total Pain Index. After 4 weeks of treatment, about 40% of group W240 patients were free of pain whether or not they had to resort to supplementary treatments. In group W120 as a whole, about 19% of patients were pain-free at 4 weeks, but only 8% of those who did not resort to supplementary treatment. In group C, 18% of patients were painfree. These findings were reflected reasonably well in the changes in the Arhus Index and Total Pain Index, and the findings in group W240 were consistent with those in a previous randomised controlled trial. Multivariable modelling to examine for possible confounding effects tended to identify membership of group W240 as an independent explanator of better pain relief than membership of group C. Though the measures of effect tended to be similar in group W120 as a whole and group C, the avoidance of more expensive conventional treatments in group W120 meant that the average cost per patient of treatment was reduced by about 35-50% (health service and private costings respectively). The better pain relief in group W240 was accompanied by an even smaller reliance on supplementary conventional treatments than in group W120 but the extra savings on these were outweighed by the extra cost of the additional Assalix so that the average cost per patient was reduced by 14-40% of the costs in group C. The possibility is discussed that, if orthopedists had relied more on regular full dosing with NSAIDs, they might have increased the effectiveness and reduced the cost of their treatment, though with the possibility of more side effects. Substituting established NSAIDs with COX-2 inhibitors might reduce the side effects, but at greater cost than with the Assalix.     

A rat model of bone cancer pain induced by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells

This study described a modified rat model of bone cancer pain. Syngeneic Walker 256 mammary gland carcinoma cells were injected into the tibia medullary cavity via intercondylar eminence. Series of tests were carried out including bone radiology, bone histology, ambulatory pain, thermal hyperalgesia, mechanical allodynia, weight bearing ability, and electrophysiological recording from primary afferent fibers. The rats inoculated with carcinoma cells showed significant ambulatory pain, mechanical allodynia, and reduction in weight bearing, as well as increased incidence of spontaneous activity in Abeta fibers in affected limb, whereas PBS (vehicle) or heat-killed cells (sham) injected rats showed no significant difference in comparison to normal rats. The pain hypersensitive behaviors were aggravated with time and destruction of bone. Interestingly, mechanical allodynia was also observed in the contralateral limb, indicating the involvement of 'mirror image' pain in bone cancer pain. In summary, the present study provided a useful and easily established rat model of bone cancer pain which will contribute to further study of the mechanisms underlying cancer pain.     

Raised circulating tenascin-C in rheumatoid arthritis

Introduction

The aim of this study was to examine whether circulating levels of the pro-inflammatory glycoprotein tenascin-C (TNC) are elevated in musculoskeletal disorders including rheumatoid arthritis (RA) and to assess in RA whether levels are related to clinical disease status and/or patient response to treatment.

Methods

TNC in serum or plasma was quantified by ELISA. Samples from 4 cohorts of RA patients were examined and compared to normal human subjects and to patients with other inflammatory diseases.

Results

Circulating TNC levels were significantly raised in patients with RA, as well as patients with systemic lupus erythematosus, idiopathic inflammatory myositis, psoriatic arthritis and ankylosing spondylitis, whilst patients with Sjogren''s syndrome displayed levels similar to healthy controls. The highest levels of TNC were observed in RA patients with late stage disease. In early disease TNC levels correlated positively with ultrasound determined erosion scores. Treatment of early RA patients with infliximab plus methotrexate (MTX) resulted in a transient decrease in circulating TNC over the first year of therapy. In contrast, TNC levels increased over time in RA patients receiving MTX alone. In patients treated with infliximab plus MTX, baseline TNC levels significantly correlated with tender joint counts (TJC) at 18 and 54 weeks after initiation of infliximab therapy.

Conclusions

Raised circulating TNC levels are detected in specific inflammatory diseases. Levels are especially high in RA where they may act as a biomarker of bone erosion and a predictor of the effect of infliximab on RA patient joint pain.     

Method for Assessing Therapeutic Potential of Anti-inflammatory Antirheumatic Drugs in Rheumatoid Arthritis

A 14-day, single-blind trial of prednisone, aspirin, and placebo was carried out in 128 patients suffering from rheumatoid arthritis, using subjective criteria only (severity of pain daily on a pain chart and assessment of the drug for effectiveness). The average treated pain rating, mean patient satisfaction rating, and mean number of days withdrawn from each drug all showed significant differences between prednisone, aspirin, and placebo. Of various pretreatment observations, only the initial pain score and articular index of joint tenderness were significantly related to the average treated pain rating.The trial method is simple and allows many patients to participate without being time consuming for patient or physician. The method seems to have potential in comparing the comparative effectiveness of anti-inflammatory analgesics used in the treatment of patients with rheumatoid arthritis.     

Defining Immunological Impact and Therapeutic Benefit of Mild Heating in a Murine Model of Arthritis

Traditional treatments, including a variety of thermal therapies have been known since ancient times to provide relief from rheumatoid arthritis (RA) symptoms. However, a general absence of information on how heating affects molecular or immunological targets relevant to RA has limited heat treatment (HT) to the category of treatments known as “alternative therapies”. In this study, we evaluated the effectiveness of mild HT in a collagen-induced arthritis (CIA) model which has been used in many previous studies to evaluate newer pharmacological approaches for the treatment of RA, and tested whether inflammatory immune activity was altered. We also compared the effect of HT to methotrexate, a well characterized pharmacological treatment for RA. CIA mice were treated with either a single HT for several hours or daily 30 minute HT. Disease progression and macrophage infiltration were evaluated. We found that both HT regimens significantly reduced arthritis disease severity and macrophage infiltration into inflamed joints. Surprisingly, HT was as efficient as methotrexate in controlling disease progression. At the molecular level, HT suppressed TNF-α while increasing production of IL-10. We also observed an induction of HSP70 and a reduction in both NF-κB and HIF-1α in inflamed tissues. Additionally, using activated macrophages in vitro, we found that HT reduced production of pro-inflammatory cytokines, an effect which is correlated to induction of HSF-1 and HSP70 and inhibition of NF-κB and STAT activation. Our findings demonstrate a significant therapeutic benefit of HT in controlling arthritis progression in a clinically relevant mouse model, with an efficacy similar to methotrexate. Mechanistically, HT targets highly relevant anti-inflammatory pathways which strongly support its increased study for use in clinical trials for RA.     

Substance P and Chronic Pain in Patients with Chronic Inflammation of Connective Tissue

Objective

Evidence suggests that substance P (SP) is involved in chronic joint inflammation, such as the pathogenesis of rheumatoid arthritis and osteoarthritis. The goal of the research was to evaluate the correlation between chronic pain and changes in the SP level in patients with chronic inflammation of the connective tissue.

Methods

Patients with osteoarthritis and rheumatoid arthritis were enrolled in this study. The relationship between chronic pain intensity and the serum SP concentration was evaluated in these groups of patients with osteoarthritis and rheumatoid arthritis.

Results

The results showed a positive correlation between the serum SP concentrations and chronic pain intensity.

Conclusions

1. The SP serum concentration was significantly different between the groups of patients with OA and RA. 2. There was a positive correlation between the serum SP concentration and chronic pain intensity in OA and RA patients.