Time since onset might be of essence: a recommendation to assess the effects of combination of non-pharmacological neuromodulatory approaches at early stage since symptoms onset

In the past decade researchers began to assess the potential beneficial effects of non-invasive brain stimulation (NIBS) combined with a behavioral task as a treatment approach for various medical conditions. Transcranial direct current stimulation (tDCS) applied to the motor cortex combined with another treatment approach has been assessed as analgesic treatment in neuropathic and non-neuropathic pain conditions, and was found to exert only modest pain relief. Our group results show that combined tDCS and mirror therapy dramatically reduced acute phantom limb pain intensity with long-lasting effects, potentially preventing pain chronification. A review of the scientific literature indicates that our approach differs from that of others: We applied the intervention at the acute stage of the disease, whereas other studies applied the intervention in patients whose disease had already been established. We suggest that the timing of administration of the combined intervention is critical. Unlike in patients with chronic painful condition, in which the maladaptive plasticity associated with pain chronification and chronicity is well-consolidated, early treatment at the acute pain stage may be more successful in counterbalancing the not-yet consolidated maladaptive plasticity. We encourage the research community to test our hypothesis, both in the treatment of pain, and beyond.info:eu-repo/semantics/publishedVersio

Non-invasive Transcranial Magnetic Stimulation (TMS) of the Motor Cortex for Neuropathic Pain—At the Tipping Point?

The term “neuropathic pain” (NP) refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation) was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain’s surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS). Repeated sessions of many TMS pulses (rTMS) can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include “frameless stereotactic” neuronavigation systems, in which patients’ head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials

No relationships between the within-subjects' variability of pain intensity reports and variability of other bodily sensations reports

Purpose: The subjective nature of pain assessment and its large variance negatively affect patient-health care provider communication and reduce the assay sensitivity of pain clinical trials. Given the lack of an objective gold standard measure, identifying the source (true or error) of the within-subject variability of pain reports is a challenge. By assessing the within-subjects variability of pain and taste reports, alongside with interoceptive measures, the current study is aimed to investigate if the ability to reliably report bodily sensations is a cross-modal characteristic. Patients and Methods: This prospective study enrolled healthy volunteers from local universities. After consenting, subjects underwent the Focus Analgesia Selection Task (FAST), to assess within-subjects variability of pain reports in response to experimental noxious stimuli; a taste task, which similarly assesses within-subjects variability of tastes (salty and sweet) intensity reports; and the heartbeat perception task, an interoceptive task aimed to assess how accurate subjects are in monitoring and reporting their own heartbeat. In addition, all subjects completed the Multidimensional Assessment of Interoceptive Awareness (MAIA), the Perceived Stress Scale (PSS), and Hospital Anxiety and Depression Scale (HADS). Spearman's correlations were used to assess relations between all measures. Results: Sixty healthy volunteers were recruited. Variability of intensity reports of different modalities were independent of each other (P > 0.05 for all correlations). The only correlation found was within modality, between variability of intensity reports of salt and sweet tastes (Spearman's r = 0.477, P < 0.001). No correlations were found between any of the task results and questionnaire results. Conclusion: Within-subjects variability of pain reports do not relate to variability of reports of other modalities or to interoceptive awareness. Further research is ongoing to investigate the clinical relevance of within-subjects' variability of pain reports.info:eu-repo/semantics/publishedVersio

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134867/1/ajad12459.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134867/2/ajad12459_am.pd

Relations between short-term memory and the within-subject variability of experimental pain intensity reports

While factors contributing to between-subjects differences in pain have been studied extensively, factors contributing to the within-subjects variability of pain reports are yet unexplored. The aim of this investigation was to assess possible associations between short-term memory and the within-subjects variability of pain reports in healthy and chronic pain patients. Healthy participants were recruited at the University of Haifa, Israel, and Fibromyalgia patients were recruited at a rheumatology department in a central hospital in Lisbon, Portugal. Following consent, both cohorts underwent the same procedures, including the digit-span test, assessing short-term memory, and the FAST procedure, assessing within-subject variability of pain intensity reports in response to experimental pain. One-hundred twenty-one healthy volunteers and 29 Fibromyalgia patients completed the study. While a significant correlation was found between the within-subjects variability and the total score of the short-term memory task (Spearman’s r = 0.394, P = 0.046) in the Fibromyalgia group, a marginal correlation emerged in the healthy cohort (r = 0.174, P = 0.056). A possible interpretation of these results is that in the patients’ group, at least some of the within-subjects variability of pain intensity reports might be due to error measurement derived by poorer short-term memory, rather than true fluctuations in perception.info:eu-repo/semantics/publishedVersio

Pain Intensity Recognition Rates via Biopotential Feature Patterns with Support Vector Machines

Background: The clinically used methods of pain diagnosis do not allow for objective and robust measurement, and physicians must rely on the patient’s report on the pain sensation. Verbal scales, visual analog scales (VAS) or numeric rating scales (NRS) count among the most common tools, which are restricted to patients with normal mental abilities. There also exist instruments for pain assessment in people with verbal and / or cognitive impairments and instruments for pain assessment in people who are sedated and automated ventilated. However, all these diagnostic methods either have limited reliability and validity or are very time-consuming. In contrast, biopotentials can be automatically analyzed with machine learning algorithms to provide a surrogate measure of pain intensity. Methods: In this context, we created a database of biopotentials to advance an automated pain recognition system, determine its theoretical testing quality, and optimize its performance. Eighty-five participants were subjected to painful heat stimuli (baseline, pain threshold, two intermediate thresholds, and pain tolerance threshold) under controlled conditions and the signals of electromyography, skin conductance level, and electrocardiography were collected. A total of 159 features were extracted from the mathematical groupings of amplitude, frequency, stationarity, entropy, linearity, variability, and similarity. Results: We achieved classification rates of 90.94% for baseline vs. pain tolerance threshold and 79.29% for baseline vs. pain threshold. The most selected pain features stemmed from the amplitude and similarity group and were derived from facial electromyography. Conclusion: The machine learning measurement of pain in patients could provide valuable information for a clinical team and thus support the treatment assessment