Clinical proof-of-concept results with a novel TRPA1 antagonist (LY3526318) in 3 chronic pain states.

Transient receptor potential ankyrin 1 (TRPA1) is implicated in physiological and pathological nociceptive signaling, but the clinical benefit of TRPA1 antagonists in chronic pain is not clearly demonstrated. LY3526318 is an oral, potent, and selective novel TRPA1 antagonist. The Chronic Pain Master Protocol was used to evaluate the safety and efficacy of LY3526318 in 3 randomized, placebo-controlled, proof-of-concept studies in knee osteoarthritis pain (OA), chronic low back pain (CLBP), and diabetic peripheral neuropathic pain (DPNP).

Long-term efficacy of high-frequency (10 kHz) spinal cord stimulation for the treatment of painful diabetic neuropathy: 24-Month results of a randomized controlled trial.

Aims: To evaluate the long-term efficacy of high-frequency (10 kHz) spinal cord stimulation (SCS) for treating refractory painful diabetic neuropathy (PDN).

Methods: The SENZA-PDN study was a prospective, multicenter, randomized controlled trial that compared conventional medical management (CMM) alone with 10 kHz SCS plus CMM (10 kHz SCS+CMM) in 216 patients with refractory PDN. After 6 months, participants with insufficient pain relief could cross over to the other treatment.

Effect of High-frequency (10-kHz) Spinal Cord Stimulation in Patients With Painful Diabetic Neuropathy: A Randomized Clinical Trial.

Importance: Many patients with diabetic peripheral neuropathy experience chronic pain and inadequate relief despite best available medical treatments.

Objective: To determine whether 10-kHz spinal cord stimulation (SCS) improves outcomes for patients with refractory painful diabetic neuropathy (PDN).

Design, Setting, And Participants: The prospective, multicenter, open-label SENZA-PDN randomized clinical trial compared conventional medical management (CMM) with 10-kHz SCS plus CMM.

Effects of synaptic and myelin plasticity on learning in a network of Kuramoto phase oscillators.

Models of learning typically focus on synaptic plasticity. However, learning is the result of both synaptic and myelin plasticity. Specifically, synaptic changes often co-occur and interact with myelin changes, leading to complex dynamic interactions between these processes.

Increased frequency of urine drug testing in chronic opioid therapy: rationale for strategies for enhancing patient adherence and safety.

Objective: To determine the average amount of time required to detect opioid aberrancy based upon varying frequencies of urine drug testing (UDT) in a community-based, tertiary care pain management center.

Subjects: This study was a retrospective analysis of 513 consecutive patients enrolled in a medication management program, receiving chronic opioid therapy between January 1, 2018 and December 31, 2018.

Methods: Data were extracted from medical records including age at start of the study period, sex, ethnicity, marital status, and smoking status.

The World Health Organization Disability Assessment Schedule-2.0 (WHODAS 2.0) in a chronic pain population being considered for chronic opioid therapy.

Purpose: To examine the validity of the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) for the assessment of function in a community-based sample of patients with chronic pain conditions undergoing evaluation for chronic opioid therapy.

Relationships Between Opioid Dosing, Pain Severity, and Disability in a Community-Based Chronic Pain Population: An Exploratory Retrospective Analysis.

Objective: To determine the relationship between opioid dose change, pain severity, and function in patients with chronic pain.

Design: Retrospective cohort study.

Setting: Community interdisciplinary pain management practice.

10 kHz spinal cord stimulation: a retrospective analysis of real-world data from a community-based, interdisciplinary pain facility.

Objective: To evaluate clinical outcomes and health care utilization at 12 months post spinal cord stimulator (SCS) implantation compared with baseline and a matched sample of patients receiving conventional medical management (CMM) for the treatment of low back and lower extremity pain.

Patients: A retrospective study of patients with at least 24 months of active treatment at an interdisciplinary community pain center between December 1, 2014 and December 31, 2017. Thirty-two patients receiving implantation of a high-frequency (10 kHz) SCS and 64 patients receiving CMM were identified through propensity matching at a ratio of 2:1.

The Association Between Cannabis Use and Aberrant Behaviors During Chronic Opioid Therapy for Chronic Pain.

Objective: Health care providers are likely to see an increase in the concomitant use of cannabis and opioids, particularly with the increased liberalization and ongoing research into the possible role of medical marijuana for chronic pain. Recent literature reports a prevalence of concurrent use ranging from 8.9% to 31.

Cannabis for the Treatment of Chronic Pain in the Era of an Opioid Epidemic: A Symposium-Based Review of Sociomedical Science.

Objective: This manuscript reviews medical literature published pertaining to the management of chronic pain with medical marijuana therapy (MMJ), with an emphasis on the social, medical, and legal aspects of therapy.

Design: Narrative review of peer-reviewed literature.

Methods: The 3rd Symposium on Controlled Substances and Their Alternatives for the Treatment of Pain was held in Boston on February 27, 2016, with a focus on MMJ for the treatment of chronic pain.

Conformational ensemble of human α-synuclein physiological form predicted by molecular simulations.

We perform here enhanced sampling simulations of N-terminally acetylated human α-synuclein, an intrinsically disordered protein involved in Parkinson's disease. The calculations, consistent with experiments, suggest that the post-translational modification leads to the formation of a transient amphipathic α-helix. The latter, absent in the non-physiological form, alters protein dynamics at the N-terminal and intramolecular interactions.

Structural predictions of neurobiologically relevant G-protein coupled receptors and intrinsically disordered proteins.

G protein coupled receptors (GPCRs) and intrinsic disordered proteins (IDPs) are key players for neuronal function and dysfunction. Unfortunately, their structural characterization is lacking in most cases. From one hand, no experimental structure has been determined for the two largest GPCRs subfamilies, both key proteins in neuronal pathways.

A molecular dynamics simulation-based interpretation of nuclear magnetic resonance multidimensional heteronuclear spectra of α-synuclein·dopamine adducts.

Multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy provides valuable structural information about adducts between naturally unfolded proteins and their ligands. These are often highly pharmacologically relevant. Unfortunately, the determination of the contributions to observed chemical shifts changes upon ligand binding is complicated.