The American Society of Pain and Neuroscience (ASPN) practical guidelines to study design and scientific manuscript preparation in neuromodulation

Background: Healthcare clinical and even policy decisions are progressively made based on research-based evidence. The process by which the appropriate trials are developed and well-written manuscripts by means of evidence-based medicine recommendations has resulted in unprecedented necessity in evidence-based medicine in neuromodulation. Methods: The essential considerations in the planning of neuromodulation research are discussed in the light of available scientific literature as well as the authors\u27 scientific expertise regarding research study design and scientific manuscript preparation. Conclusion: This article should enable the reader to understand how to appropriately design a clinical research study and prepare scientific manuscripts. The high-quality and well-designed studies, when performed and reported effectively, support evidence-based medicine and foster improved patient outcomes

Characterizing Abdominal Pain in Patients With Gastroparesis Into Neuropathic and Nociceptive Components.

INTRODUCTION: The cause of abdominal pain (AP) in gastroparesis (Gp) is often not known; hence, its treatment can be challenging. Preoccupation with or increased attention (hypervigilance) to pain is associated with perceived pain severity and psychosocial disability. The aims of this study were to (1) characterize AP in Gp patients into neuropathic and nociceptive pain components; (2) assess these patients for hypervigilance to pain. MATERIALS AND METHODS: Gp patients with AP as an important symptom, seen from June 2017 to November 2017 were given validated questionnaires to characterize their AP. Carnett\u27s sign (worsened AP/tenderness on head/shoulder lift and/or leg lift) was assessed on examination. RESULTS: Of 32 patients (87% females), 20 had idiopathic Gp, and 9 had diabetic Gp. AP severity using Patient Assessment of Gastrointestinal Symptoms averaged 4.3±0.2 (standard error of mean) for upper AP and 2.3±0.3 for lower AP. AP was typically located in epigastrium (53.1%), and described as sharp (75%). Eleven patients (35.5%) met criteria for neuropathic pain on Neuropathic Pain Questionnaire. Twenty patients (62.5%) had positive Carnett\u27s sign suggesting somatic pain. Fifteen patients (48.4%) were hypervigilant to pain on Pain Vigilance and Awareness Questionnaire. CONCLUSIONS: Of Gp patients with AP, over one third have a neuropathic component to their pain whereas nearly two thirds have characteristics of somatic pain. Almost half of the Gp patients with AP are hypervigilant to pain. Determining the underlying cause of AP and hypervigilance to pain in Gp patients may assist in devising appropriate treatment strategies

Serum uric acid in U.S. adolescents: distribution and relationship to demographic characteristics and cardiovascular risk factors.

BACKGROUND: Despite being associated with multiple disease processes and cardiovascular outcomes, uric acid (UA) reference ranges for adolescents are lacking. We sought to describe the distribution of UA and its relationship to demographic, clinical, socioeconomic, and dietary factors among U.S. adolescents. METHODS: A nationally representative subsample of 1,912 adolescents aged 13-18 years in NHANES 2005-2008 representing 19,888,299 adolescents was used for this study. Percentiles of the distribution of UA were estimated using quantile regression. Linear regression models examined the association of UA and demographic, socioeconomic, and dietary factors. RESULTS: Mean UA level was 5.14 ± 1.45 mg/dl. Mean UA increased with increasing age and was higher in non-Hispanic white race, male sex, higher body mass index (BMI) Z-score, and with higher systolic blood pressure. In fully adjusted linear regression models, sex, age, race, and BMI were independent determinants of higher UA. CONCLUSIONS: This study defines serum UA reference ranges for adolescents. Also, it reveals some intriguing relationships between UA and demographic and clinical characteristics that warrant further studies to examine the pathophysiological role of UA in different disease processes

Development of an Educational Curriculum for Spinal Cord Stimulation.

BACKGROUND: Spinal cord stimulators (SCSs) are used for treating chronic pain. The number of SCSs implanted each year is on the increase. The North American Neuromodulation Society (NANS) education committee aimed to develop a SCS curriculum as a tool to guide physicians at different training levels, based on the most recent evidence. MATERIAL AND METHODS: A multidisciplinary (anesthesiology, physical medicine, neurosurgery, and neurology), taskforce representing the education committee of the NANS met to develop a SCS curriculum following the Accreditation Council for Graduate Medical Education (ACGME) milestones. The task force used the best available evidence and knowledge to develop the curriculum. Once developed, the SCS curriculum was then approved by the NANS board. RESULTS: The task force developed a SCS training curriculum. Milestones included patient care and procedural skills, system-based practice, medical knowledge, interpersonal communication, practice based learning and professionalism. Each milestone was defined for three categories, early learner, advanced learner, and practitioner. CONCLUSION: A multidisciplinary task force of the NANS education committee developed a SCS training curriculum that defines ACGME milestones for basic learners, advanced learners, and practitioners

Plasma kallikrein promotes epidermal growth factor receptor transactivation and signaling in vascular smooth muscle through direct activation of protease-activated receptors.

The kallikrein-kinin system, along with the interlocking renin-angiotensin system, is a key regulator of vascular contractility and injury response. The principal effectors of the kallikrein-kinin system are plasma and tissue kallikreins, proteases that cleave high molecular weight kininogen to produce bradykinin. Most of the cellular actions of kallikrein (KK) are thought to be mediated by bradykinin, which acts via G protein-coupled B1 and B2 bradykinin receptors on VSMCs and endothelial cells. Here, we find that primary aortic vascular smooth muscle but not endothelial cells possess the ability to activate plasma prekallikrein. Surprisingly, exposing VSMCs to prekallikrein leads to activation of the ERK1/2 mitogen-activated protein kinase cascade via a mechanism that requires kallikrein activity but does not involve bradykinin receptors. In transfected HEK293 cells, we find that plasma kallikrein directly activates G protein-coupled protease-activated receptors (PARs) 1 and 2, which possess consensus kallikrein cleavage sites, but not PAR4. In vascular smooth muscles, KK stimulates ADAM (a disintegrin and metalloprotease) 17 activity via a PAR1/2 receptor-dependent mechanism, leading sequentially to release of the endogenous ADAM17 substrates, amphiregulin and tumor necrosis factor-α, metalloprotease-dependent transactivation of epidermal growth factor receptors, and metalloprotease and epidermal growth factor receptor-dependent ERK1/2 activation. These results suggest a novel mechanism of bradykinin-independent kallikrein action that may contribute to the regulation of vascular responses in pathophysiologic states, such as diabetes mellitus

The American Society of Pain and Neuroscience (ASPN) Practical Guidelines to Study Design and Scientific Manuscript Preparation in Neuromodulation.

BACKGROUND: Healthcare clinical and even policy decisions are progressively made based on research-based evidence. The process by which the appropriate trials are developed and well-written manuscripts by means of evidence-based medicine recommendations has resulted in unprecedented necessity in evidence-based medicine in neuromodulation. METHODS: The essential considerations in the planning of neuromodulation research are discussed in the light of available scientific literature as well as the authors\u27 scientific expertise regarding research study design and scientific manuscript preparation. CONCLUSION: This article should enable the reader to understand how to appropriately design a clinical research study and prepare scientific manuscripts. The high-quality and well-designed studies, when performed and reported effectively, support evidence-based medicine and foster improved patient outcomes

Educational Curriculum for Peripheral Nerve Stimulation Developed by the North American Neuromodulation Society.

BACKGROUND: Peripheral nerve stimulation (PNS) is an effective neuromodulation therapy for chronic neuropathic and nociceptive pain. Although the total number of PNS implantations has increased over the last decade, no curriculum exists to guide training and learning of this therapy. The goal of the North American Neuromodulation Society (NANS) education committee is to develop a series of competency-based curriculums for neuromodulation therapies. The PNS curriculum is the latest part of such series, following the curriculums for spinal cord stimulation and intrathecal drug delivery system. MATERIALS AND METHODS: A multidisciplinary task force (anesthesiology, physical medicine and rehabilitation, neurosurgery, preventive medicine and public health, and neurology) was created by the educational committee of NANS to develop a PNS curriculum in accordance with the Accreditation Council for Graduate Medical Education (ACGME) milestones. The curriculum was created based on the best available evidence and expert knowledge (from our task force members) of available PNS systems. The final PNS curriculum was approved by the NANS board. RESULTS: A PNS curriculum was developed by the task force. Milestones included professionalism, practice-based learning, interpersonal communication, medical knowledge, systems-based practice, procedural skills, and patient care. Each milestone was defined into three categories: early learner, advanced learner, and practitioner. CONCLUSIONS: This manuscript provides a PNS training curriculum developed by a multidisciplinary task force of the NANS educational committee in accordance with the milestones described by ACGME for basic learners, advanced learners, and practitioners. This curriculum will help provide a structured training and evaluation process for obtaining proficiency in PNS treatment(s)