A Prospective Six-Month Study of Chronic Pain Sufferers: A Novel OTC Neuromodulation Therapy.

Objective: To assess the durability of treatment over various chronic pain conditions of an emerging, nonprescription electromagnetic neuromodulation device that uses pulsed shortwave therapy. Methods: A 6-month prospective study, involving 240 chronic pain sufferers, 94% of whom reported using pain pills and 98% reported using pain therapies prior to entering the study. Their average baseline pain was 8.2 VAS points before treatment; they had a pain duration of 6.5 years, and they were positive responders to pulsed shortwave therapy in an initial 7-day trial. Prospective assessments were obtained at intervals of 3, 4, and 6 months following a retrospective 7-day assessment. Longitudinal analyses were conducted to determine pain relief trends after the initial 7-day device use. Results: Seven days after initial treatment, the average pain was reduced to 2.9, a 65% pain reduction for the study subjects. At the 6-month measurement, the average pain was 3.3, a 60% pain reduction from baseline. Only 17% of the subjects saw their pain level increase although this new level was still lower than baseline pain. Pain relief translated into improved quality of life and reduced medication use for the majority of the subjects. There were no significant adverse side effects reported over the 6 months of use. Conclusion: Ninety-seven percent of the recruited subjects, all of whom had previously reported clinically significant pain relief using the 7-day PSWT device, sustained this relief for 6 months by using the device on an as-needed basis.

Chronic pain intervention using pulsed shortwave therapy: the relationship between pain demographics and central sensitization inventory.

Aim: The central sensitization inventory (CSI) is a validated, patient-reported questionnaire that quantifies symptoms of hypersensitivity disorders such as chronic pain, for which central sensitization (CS) may be the etiology. Objective: To investigate the analgesic effectiveness of ActiPatch and analyze the relationship between baseline CSI scores and demographics of chronic pain sufferers. Methods: Upon completing a 7-day ActiPatch trial, baseline CSI scores along with other assessment measures were obtained via e-mail from 174 chronic pain sufferers. Conclusion: CSI scores were positively correlated with gender (higher for women), baseline visual analog scale scores and pain duration. ActiPatch was found to be effective in reducing baseline pain for all subjects by an average of 4.3 visual analog scale points.

An over-the-counter central sensitization therapy: a chronic back pain registry study of pain relief, medication use and their adverse effects.

AIM: Back pain, the most prevalent musculoskeletal chronic pain condition, is usually treated with analgesic medications of questionable efficacy and frequent occurrence of adverse side effects. OBJECTIVE: The objective was to determine the effectiveness of the ActiPatch medical devices in reducing chronic back pain, document medication related adverse side effects and establish their impact on quality of life. METHODS: Upon completing a 7-day trial, subjects were contacted via email with an assessment form using the Constant Contact email program. A total of 1394 responses were collected from subjects who used the device for back pain. CONCLUSION: Medication adverse effects are common and impact quality of life in the lay population. ActiPatch is an effective intervention for the majority of subjects for treating chronic back pain, although this requires further investigation in randomized clinical trials.

A UK registry study of the effectiveness of a new over-the-counter chronic pain therapy.

BACKGROUND: The ActiPatch(®) (BioElectronics Corporation, MD, USA) pulsed shortwave therapy device has been shown to be clinically effective in three double-blind randomized controlled pain studies. However, the effectiveness of this device in a broader population of chronic musculoskeletal pain sufferers, affected by a variety of etiologies in different regions of the body, has not been studied. AIM: The objective of this registry study was to assess the effectiveness and satisfaction of the ActiPatch device in the general population of chronic pain sufferers. METHODS: A total of 44,000 subjects completed the trial, with 5000 assessments of the device collected. CONCLUSION: The ActiPatch device appears to provide a clinically meaningful reduction of chronic musculoskeletal pain affecting different locations of the body caused by a variety of etiologies.

The case for over-the-counter shortwave therapy: safe and effective devices for pain management.

Pulsed shortwave diathermy, an electromagnetic therapy, has been in clinical use for acute and chronic musculoskeletal pain for many decades. Innovation, miniaturization and advances in technology have allowed for the development of a new generation of shortwave devices that deliver a localized, low fixed dose of shortwave therapy. Clinical research has shown that these novel shortwave devices can be used safely in order to reduce acute and chronic pain, as well as the need for pain medications. Their ease of use and safety profile make low-dose shortwave devices an attractive alternative, or adjunct therapy, to pharmacological-based pain therapies.

Discovery of putative salivary biomarkers for Sjögren's syndrome using high resolution mass spectrometry and bioinformatics.

The purpose of the current study was to determine if saliva contains biomarkers that can be used as diagnostic tools for Sjögren's syndrome (SjS). Twenty seven SjS patients and 27 age-matched healthy controls were recruited for these studies. Unstimulated glandular saliva was collected from the Wharton's duct using a suction device. Two µl of salvia were processed for mass spectrometry analyses on a prOTOF 2000 matrix-assisted laser desorption/ionization orthogonal time of flight (MALDI O-TOF) mass spectrometer. Raw data were analyzed using bioinformatic tools to identify biomarkers. MALDI O-TOF MS analyses of saliva samples were highly reproducible and the mass spectra generated were very rich in peptides and peptide fragments in the 750-7,500 Da range. Data analysis using bioinformatic tools resulted in several classification models being built and several biomarkers identified. One model based on 7 putative biomarkers yielded a sensitivity of 97.5%, specificity of 97.8% and an accuracy of 97.6%. One biomarker was present only in SjS samples and was identified as a proteolytic peptide originating from human basic salivary proline-rich protein 3 precursor. We conclude that salivary biomarkers detected by high-resolution mass spectrometry coupled with powerful bioinformatic tools offer the potential to serve as diagnostic/prognostic tools for SjS.

Pulsed radiofrequency electromagnetic field therapy: a potential novel treatment of plantar fasciitis.

Plantar fasciitis is a common cause of heel pain, and although treatments are usually conservative, they can take up to 2 years to achieve resolution. A double-blind, multicenter, randomized, placebo-controlled study was used to evaluate a small, wearable, extended-use pulsed radiofrequency electromagnetic field (PRFE) device as a treatment of plantar fasciitis. A total of 70 subjects diagnosed with plantar fasciitis were enrolled in the present study. The subjects were randomly assigned a placebo or active PRFE device. The subjects were instructed to wear the PRFE device overnight, record their morning and evening pain using a 0- to 10-point visual analog scale (VAS), and log any medication use. The primary outcome measure for the present study was morning pain, a hallmark of plantar fasciitis. The study group using the active PRFE device showed progressive decline in morning pain. The day 7 AM-VAS score was 40% lower than the day 1 AM-VAS score. The control group, in comparison, showed a 7% decline. A significantly different decline was demonstrated between the 2 groups (p = .03). The PM-VAS scores declined by 30% in the study group and 19% in the control group, although the difference was not significant. Medication use in the study group also showed a trend downward, but the use in the control group remained consistent with the day 1 levels. PRFE therapy worn on a nightly basis appears to offer a simple, drug-free, noninvasive therapy to reduce the pain associated with plantar fasciitis.

The use of a portable, wearable form of pulsed radio frequency electromagnetic energy device for the healing of recalcitrant ulcers: a case report.

Pulsed radio frequency energy (PRFE) has successfully been used to treat diabetic and venous stasis ulcers. In this case report, a lightweight wearable form of a PFRE device was evaluated and used to treat three diabetic foot ulcers and one venous stasis ulcer. The ulcers were present on the four patients for more than 3 months and had failed to heal after conventional treatment. A lightweight battery-powered, wearable form of PRFE device was introduced as a treatment and used 6-8 hours per day for a period of 6 weeks. All patients after 1 week of therapy showed improvement and wound size was seen to decrease. Patient 1 had a venous stasis ulcer, and reported significant pain relief after 2 weeks treatment. Patients 2 and 3 achieved complete healing after 3 weeks treatment, and patients 1 and 4 had a 95% and 88% reduction in wound size, respectively, after the 6-week study period. Both these patients continued to complete healing using the PRFE device after the 6-week study period. PRFE treatment delivered in the form of a wearable lightweight patch appears to offer promise in the treatment of recalcitrant chronic wounds.

Control of postoperative pain with a wearable continuously operating pulsed radiofrequency energy device: a preliminary study.

BACKGROUND: Pulsed radiofrequency energy (PRFE) has long been reported to have a therapeutic effect on postoperative pain. In this study, a portable, wearable, low-energy-emitting PRFE therapy device was used to determine the control of postoperative pain after breast augmentation surgery. METHODS: The study enrolled 18 healthy women who underwent breast augmentation purely for aesthetic considerations. Postoperative pain after surgery was assessed with a 0- to 10-point visual analog scale (VAS). Baseline pain scores were taken at completion of the operation, and the patients were randomly assigned coded PRFE devices that were either active or placebo devices. For 7 days, VAS scores were recorded twice daily (a.m. and p.m.). Medication use also was logged for 7 days. The PRFE devices were left in place and in continuous operation for the 7 days of the study. RESULTS: All the patients tolerated the PRFE therapy well, and no side effects were reported. The VAS scores for the active group were significantly lower on postoperative day 1. By day 7, the baseline VAS remaining in the active group was 7.9% versus 38% in the placebo group. Together with lower VAS scores, narcotic pain medication use was lower in the patient group that received PRFE therapy. CONCLUSION: Postoperative pain is significantly lower with PRFE therapy. According to the findings, PRFE therapy in this form is an excellent, safe, drug-free method of postoperative pain control.

Calpain activation in experimental glaucoma.

PURPOSE: Glaucoma is a neurodegenerative disease in which elevated intraocular pressure (IOP) leads to progressive loss of retinal ganglion cells (RGCs) and blindness. Calcium dyshomeostasis has been suggested to play a role in the pathologic events that lead to RGC loss, though the details of these events are not well understood. Calcium-induced activation of calpain has been shown to contribute to neuronal death in a wide variety of neurodegenerative diseases. The authors hypothesize that similar events occur in glaucoma. METHODS: The authors used a well-established rat model of experimental glaucoma. Retinal tissues were harvested after 5 or 10 days of elevated IOP and were subjected to immunoblot analysis, immunoprecipitation, and MALDI-ProTOF/MS peptide fingerprint mapping. Immunohistochemistry was used to localize calpain activation. RESULTS: The authors present four independent lines of evidence that calpain is activated in experimental glaucoma. First, they showed that a 55-kDa autocatalytic active form of calpain is detected on immunoblot analysis. Second, they demonstrated the cleavage of two well-established calpain substrates, spectrin and calcineurin, only in eyes with elevated IOP. Third, they used MALDI-ProTOF to analyze cleaved calcineurin and immunoblot analysis of spectrin cleavage products and showed that both substrates were cleaved by calpain in experimental glaucoma. Fourth, they used immunohistochemistry to show that calpain-mediated spectrin cleavage occurs in RGCs under conditions of elevated IOP. CONCLUSIONS: These data support the hypothesis that calpain is activated under conditions of elevated intraocular pressure and provide further details of the pathologic events leading to RGC loss in glaucoma.

Colocalization of increased transforming growth factor-beta-induced protein (TGFBIp) and Clusterin in Fuchs endothelial corneal dystrophy.

PURPOSE: To investigate the differential expression of TGFBIp in normal human and Fuchs endothelial corneal dystrophy (FECD) endothelial cell-Descemet's membrane (HCEC-DM) complex, and to asses the structural role of TGFBIp and clusterin (CLU) in guttae formation. METHODS: HCEC-DM complex was dissected from stroma in normal and FECD samples. Proteins were separated by 2-D gel electrophoresis and subjected to proteomic analysis. N-terminal processing of TGFBIp was detected by Western blot analysis with two separate antibodies against the N- and C-terminal regions of TGFBIp. Expression of TGFBI mRNA was compared by using real-time PCR. Subcellular localization of TGFBIp and CLU in corneal guttae was assessed by fluorescence confocal microscopy. RESULTS: A major 68-kDa fragment and a minor 39-kDa fragment of TGFBIp were identified on 2-D gels. Western blot analysis revealed an age-dependent proteolytic processing of the TGFBIp N terminus resulting in the increased formation of 57-kDa (P = 0.04) and 39-kDa (P = 0.03) fragments in older donors. FECD HCEC-DM showed a significant increase in the 68-kDa (P = 0.04), 57-kDa (P = 0.01), and 39- kDa (P = 0.03) fragments of TGFBIp. Real-time PCR analysis revealed that TGFBI mRNA was significantly increased (P = 0.04) in FECD samples. TGFBIp formed aggregates at the lower portions of guttae, next to Descemet's membrane, whereas CLU localized mostly on top of the TGFBIp-stained areas at the level of the endothelial cell nuclear plane. CONCLUSIONS: The overexpression of proaggregative protein CLU, and proadhesive protein TGFBIp, have been colocalized in the guttae. Such findings provide us with a better understanding of the major contributors involved in the aberrant cell-extracellular matrix interactions seen in the guttae of patients with FECD.

Differential protein expression in human corneal endothelial cells cultured from young and older donors.

PURPOSE: To establish a baseline protein fingerprint of cultured human corneal endothelial cells (HCEC), to determine whether the protein profiles exhibit age-related differences, and to identify proteins differentially expressed in HCEC cultured from young and older donors. METHODS: Corneas were obtained from five young (<30 years old) and five older donors (>50 years old). HCEC were cultured, and protein was extracted from confluent passage 3 cells. Extracts from each age group were pooled to form two samples. Proteins were separated on two-dimensional (2-D) gels and stained with SyproRuby. Resultant images were compared to identify protein spots that were either similarly expressed or differentially expressed by at least twofold. Protein spots were then identified by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. RESULTS: Protein spots were well resolved, and patterns were reproducible on 2-D gels using either pH 3-10 or pH 4-7 IPG strips. Two-dimensional gels prepared with pH 4-7 IPG strips were used for differential display analysis, which was reproduced on three separate pairs of gels. MALDI-TOF identified 58 proteins with similar expression; 30 proteins were expressed twofold higher in HCEC from young donors; five proteins were expressed twofold higher in cells from older donors; and 10 proteins were identified in gels from young donors that did not match in gels from older donors. Several proteins expressed at higher levels in younger donors support metabolic activity, protect against oxidative damage, or mediate protein folding or degradation. CONCLUSIONS: This is the first proteomic comparison of proteins expressed in HCEC cultured from young and older donors. Although restricted to proteins with isoelectric points between pH 4.0 and pH 7.0, the data obtained represent an initial step in the investigation of molecular mechanisms that underlie physiologically important age-related differences in cultured HCEC, including differences that may affect proliferative capacity. Results indicate that HCEC from older donors exhibit reduced expression of proteins that support important cellular functions such as metabolism, antioxidant protection, protein folding, and protein degradation. These differences may affect the ability to consistently obtain a sufficient number of healthy cultured HCEC for use in preparing bioengineered endothelium as an alternative method for the treatment of endothelial dysfunction.

Decreased expression of peroxiredoxins in Fuchs' endothelial dystrophy.

PURPOSE: To compare the relative expression of peroxiredoxin (Prx) proteins in normal human corneal endothelium with endothelium in corneas affected by Fuchs' endothelial dystrophy (FED) and between normal human endothelium and epithelial/stromal tissue. METHODS: Human corneal endothelial cell-Descemet's membrane (HCEC-DM) complexes from normal and FED corneal buttons were dissected from the epithelium/stroma. For proteomic analysis, HCEC-DM protein extracts were separated by using two-dimensional gel electrophoresis. Relative differences in protein spot density was analyzed. Proteins of interest, including Prx isoforms, were identified by MALDI-TOF (matrix-assisted desorption ionization-time of flight) mass spectrometry. Western blot analysis compared the relative expression of Prx isoforms in normal and FED endothelium and between normal endothelium and normal epithelium/stroma. Expression of Prx-2 mRNA was compared by using real-time PCR. RESULTS: Proteomic analysis identified differences in the relative expression of Prx isoforms between normal and FED endothelium. Western blot analysis confirmed that expression of Prx-2, -3, and -5 was significantly decreased (P < 0.05) in FED cells. Normal HCECs expressed significantly (P < 0.05) higher levels of Prx-2 and -3 than did the epithelium/stroma. Expression of Prx-5 was not significantly different (P > 0.05) in the endothelium versus the epithelium/stroma. Real-time PCR analysis revealed that Prx-2 mRNA was significantly decreased (P = 0.027) in FED samples. CONCLUSIONS: Prx proteins were identified in human corneal endothelium. The fact that Prx-2 and -3 were expressed at significantly higher levels in HCEC-DM compared with the epithelium/stroma reflects the different physiologic activities of individual corneal cell types. Significantly decreased expression of Prx-2, -3, and -5 in FED may suggest an alteration in the ability of endothelial cells to withstand oxidant-induced damage and may be closely related to the pathogenesis of this disease.

Increased clusterin expression in Fuchs' endothelial dystrophy.

PURPOSE: To investigate the differential expression of the glycoprotein clusterin/apoJ (CLU) in normal and Fuchs' endothelial dystrophy (FED) corneal endothelium and to compare the expression of various forms of CLU in normal and FED tissue. METHODS: FED and pseudophakic bullous keratopathy (PBK) corneal buttons were removed during transplantation, and normal corneas were obtained from tissue banks. Human corneal endothelial cells and Descemet's membrane (HCEC-DM) complex was dissected from the stroma. Proteins were separated on 2-D gels and subjected to comparative proteomic analysis. Relative expression of presecretory CLU (pre-sCLU), secretory (s)CLU, and nuclear (n)CLU were compared between normal and FED HCEC-DM by Western blot analysis. Expression of CLU mRNA was compared by using RT-PCR. Subcellular localization of CLU was compared in corneal wholemounts from normal eyes and eyes with FED by immunocytochemistry followed by confocal microscopy. RESULTS: Proteomic analysis revealed an apparent increase in CLU expression in FED HCEC-DM compared with the normal control. Western blot analysis demonstrated that pre-sCLU protein expression was 5.2 times higher in FED than in normal samples (P = 3.52E-05), whereas the mature form modified for secretion (sCLU) was not significantly elevated (P = 0.092). Expression of nCLU protein was significantly elevated in FED (P = 0.013). RT-PCR analysis revealed that CLU mRNA was significantly increased (P = 0.002) in FED samples, but not in PBK samples. CLU also had a distinctive localization in FED samples with enhanced intracellular staining around the guttae and in the nuclei of endothelial cells. CONCLUSIONS: CLU expression is markedly elevated in FED-affected tissue, pointing to a yet undiscovered form of dysregulation of endothelial cell function involved in FED pathogenesis.