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Dora Janela,1 Fabíola Costa,1 Maria Molinos,1 Robert G Moulder,2 Jorge Lains,3,4 Gerard E Francisco,5 Virgílio Bento,1 Steven P Cohen,6,7 Fernando Dias Correia1,8 1SWORD Health Technologies, Inc, Clinical Validation, Draper, UT, USA; 2Institute for Cognitive Science, University of Colorado Boulder, Boulder, CO, USA; 3Rovisco Pais Medical and Rehabilitation Centre, Tocha, Portugal; 4Faculty of Medicine, Coimbra University, Coimbra, Portugal; 5Department of Physical Medicine and Rehabilitation, The University of Texas Health Science Center McGovern Medical School, and TIRR Memorial Hermann, Houston, TX, USA; 6Departments of Anesthesiology & Critical Care Medicine, Physical Medicine and Rehabilitation, Neurology, and Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA; 7Departments of Anesthesiology and Physical Medicine and Rehabilitation and Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA; 8Neurology Department, Centro Hospitalar e Universitário do Porto, Porto, PortugalCorrespondence: Fernando Dias CorreiaSWORD Health Technologies, Inc, Clinical Validation, 65 E Wadsworth Park Dr Ste 230, Draper, UT, 84020, USATel +1 385-308-8034Fax +1 801-206-3433Email fcorreia@swordhealth.comBackground: Chronic shoulder pain (SP) is responsible for significant morbidity, decreased quality of life and impaired work ability, resulting in high socioeconomic burden. Successful SP management is dependent on adherence and compliance with effective evidence-based interventions. Digital solutions may improve accessibility to such treatments, increasing convenience, while reducing healthcare-related costs.Purpose: Present the results of a fully remote digital care program (DCP) for chronic SP.Patients and Methods: Interventional, single-arm, cohort study of individuals with chronic SP applying for a digital care program. Primary outcome was the mean change between baseline and 12 weeks on the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) questionnaire. Secondary outcomes were change in pain (NPRS), analgesic consumption, intention to undergo surgery, anxiety (GAD-7), depression (PHQ-9), fear-avoidance beliefs (FABQ-PA), work productivity (WPAI) and engagement.Results: From 296 patients at program start, 234 (79.1%) completed the intervention. Changes in QuickDASH between baseline and end-of-program were both statistically (p < 0.001) and clinically significant, with a mean reduction of 51.6% (mean − 13.45 points, 95% CI: 11.99; 14.92). Marked reductions were also observed in all secondary outcomes: 54.8% in NPRS, 44.1% ceased analgesics consumption, 55.5% in surgery intent, 37.7% in FABQ-PA, 50.3% in anxiety, 63.6% in depression and 66.5% in WPAI overall. Higher engagement was associated with higher improvements in disability. Mean patient satisfaction score was 8.7/10.0 (SD 1.6).Conclusion: This is the first real-world cohort study reporting the results of a multimodal remote digital approach for chronic SP rehabilitation. High completion and engagement rates were observed, which were associated with clinically significant improvement in all health-related outcomes, as well as marked productivity recovery. These promising results support the potential of digital modalities to address the global burden of chronic musculoskeletal pain.Keywords: chronic pain, physical therapy, telerehabilitation, digital therapeutic, eHealth

David E Jamison,1,2 Steven P Cohen1–6 1Department of Anesthesiology, Walter Reed National Military Medical Center (WRNMMC), Bethesda, MD, USA; 2Department of Anesthesiology, Uniformed Services University of Health Sciences (USUHS), Bethesda, MD, USA; 3Department of Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA; 4Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA; 5Department of Physical Medicine and Rehabilitation, Johns Hopkins School of Medicine, Baltimore, MD, USA; 6Department of Physical Medicine and Rehabilitation, USUHS, Bethesda, MD, USA Background: The use of radiofrequency ablation (RFA) procedures to treat chronic knee pain has surged in the past decade, though many questions remain regarding anatomical targets, selection criteria, and evidence for effectiveness. Methods: A comprehensive literature review was performed on anatomy, selection criteria, technical parameters, results of clinical studies, and complications. Databases searched included MEDLINE and Google Scholar, with all types of clinical and preclinical studies considered. Results: We identified nine relevant clinical trials, which included 592 patients, evaluating knee RFA for osteoarthritis and persistent postsurgical pain. These included one randomized, placebo-controlled trial, one randomized controlled trial evaluating RFA as add-on therapy, four comparative-effectiveness studies, two randomized trials comparing different techniques and treatment paradigms, and one non-randomized, controlled trial. The results of these studies demonstrate significant benefit for both reduction and functional improvement lasting between 3 and 12 months, with questionable utility for prognostic blocks. There was considerable variation in the described neuroanatomy, neural targets, radiofrequency technique, and selection criteria. Conclusion: RFA of the knee appears to be a viable and effective treatment option, providing significant benefit to well-selected patients lasting at least 3 months. More research is needed to better identify neural targets, refine selection criteria to include the use of prognostic blocks, optimize treatment parameters, and better elucidate relative effectiveness compared to other treatments. Keywords: Knee pain, osteoarthritis, radiofrequency, ablation, denervation, genicular nerve

David S Chang,1 Eugene Hsu,2 Daniel G Hottinger,1 Steven P Cohen1,3–5 1Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 2Clinical Excellence Research Center, Stanford University School of Medicine, Stanford, CA, 3Department of Anesthesiology, 4Department of Physical Medicine and Rehabilitation, Uniformed Services University of the Health Sciences, Bethesda 5Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: There continues to be an unmet need for safe and effective pain medications. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) dominate the clinical landscape despite limited effectiveness and considerable side-effect profiles. Although significant advancements have identified myriad potential pain targets over the past several decades, the majority of new pain pharmacotherapies have failed to come to market. The discovery of nerve growth factor (NGF) and its interaction with tropomyosin receptor kinase A (trkA) have been well characterized as important mediators of pain initiation and maintenance, and pharmacotherapies targeting this pathway have the potential to be considered promising methods in the treatment of a variety of nociceptive and neuropathic pain conditions. Several methodologic approaches, including sequestration of free NGF, prevention of NGF binding and trkA activation, and inhibition of trkA function, have been investigated in the development of new pharmacotherapies. Among these, NGF-sequestering antibodies have exhibited the most promise in clinical trials. However, in 2010, reports of rapid joint destruction leading to joint replacement prompted the Food and Drug Administration (FDA) to place a hold on all clinical trials involving anti-NGF antibodies. Although the FDA has since lifted this hold and a number of new trials are under way, the long-term efficacy and safety profile of anti-NGF antibodies are yet to be established. Keywords: nociceptive pain, neuropathic pain, drug discovery, tanezumab, fulranumab, fasinumab

Eugene Hsu,1 Steven P Cohen21Johns Hopkins School of Medicine, Baltimore, MD, USA; 2Johns Hopkins School of Medicine and Uniformed Services, University of the Health Sciences, Bethesda, MD, USAAbstract: Postamputation pain (PAP) is highly prevalent after limb amputation but remains an extremely challenging pain condition to treat. A large part of its intractability stems from the myriad pathophysiological mechanisms. A state-of-art understanding of the pathophysiologic basis underlying postamputation phenomena can be broadly categorized in terms of supraspinal, spinal, and peripheral mechanisms. Supraspinal mechanisms involve somatosensory cortical reorganization of the area representing the deafferentated limb and are predominant in phantom limb pain and phantom sensations. Spinal reorganization in the dorsal horn occurs after deafferentation from a peripheral nerve injury. Peripherally, axonal nerve damage initiates inflammation, regenerative sprouting, and increased "ectopic" afferent input which is thought by many to be the predominant mechanism involved in residual limb pain or neuroma pain, but may also contribute to phantom phenomena. To optimize treatment outcomes, therapy should be individually tailored and mechanism based. Treatment modalities include injection therapy, pharmacotherapy, complementary and alternative therapy, surgical therapy, and interventions aimed at prevention. Unfortunately, there is a lack of high quality clinical trials to support most of these treatments. Most of the randomized controlled trials in PAP have evaluated medications, with a trend for short-term efficacy noted for ketamine and opioids. Evidence for peripheral injection therapy with botulinum toxin and pulsed radiofrequency for residual limb pain is limited to very small trials and case series. Mirror therapy is a safe and cost-effective alternative treatment modality for PAP. Neuromodulation using implanted motor cortex stimulation has shown a trend toward effectiveness for refractory phantom limb pain, though the evidence is largely anecdotal. Studies that aim to prevent PAP using epidural and perineural catheters have yielded inconsistent results, though there may be some benefit for epidural prevention when the infusions are started more than 24 hours preoperatively and compared with nonoptimized alternatives. Further investigation into the mechanisms responsible for and the factors associated with the development of PAP is needed to provide an evidence-based foundation to guide current and future treatment approaches.Keywords: phantom pain, stump pain, residual limb pain

Five groups of subjects, two monolingual in English or French, three bilingual in French and English, but one native in English, the second native in French, and the third native in both languages, were measured for their accuracy in perceiving initial phoneme sequences. All groups were most accurate in perceiving sequences that occurred in both languages and least accurate with sequences occurring in neither language. Sequences occurring in one of the two languages fell between these extremes with French sequences yielding significantly higher accuracy than English sequences. The bilinguals who were native in English or native in both languages were superior to the other three groups on the tasks. Errors tended to be distortions in the direction of the subject's native language. The most common error was a replacement of the initial phoneme accompanied by accurate perception of the second phoneme.