Use of spinal cord stimulation for the treatment of post total knee arthroplasty pain.

Total knee arthroplasty (TKA), a common elective surgical procedure, is indicated in patients with knee pain that becomes refractory to nonsurgical interventions, such as weight loss, physical activity, physical therapy, and pharmacologic treatment. However, postoperative chronic pain is frequently reported and may lead to opioid use and dependence. Due to the increasing concern of the overuse of opioids in medical treatments, a search for other viable options is recognized. As a consequence, alternative therapies, such as transcutaneous electrical nerve stimulation (TENS), pulsed radiofrequency (PRF), and spinal cord stimulation (SCS) are being tried to potentially replace traditional opioid use in treating persistent postsurgical pain (PPSP), thus reducing opioid dependence across the nation. Here, we provide a brief overview of persistent pain following TKA procedures, with a particular emphasis on the role of promising therapies, such as TENS, PRF, and SCS for the treatment of post-TKA pain.

Predicting and validating a model of suppressor of IKKepsilon through biophysical characterization.

Suppressor of IKKepsilon (SIKE) is a 207 residue protein that is implicated in the TLR3-TANK-binding kinase-1-mediated response to viral infection. SIKE's function in this pathway is unknown, but SIKE forms interactions with two distinct cytoskeletal proteins, α-actinin and tubulin, and SIKE knockout reduces cell migration. As structure informs function and in the absence of solved structural homologs, our studies were directed toward creating a structural model of SIKE through biochemical and biophysical characterization to probe and interrogate SIKE function. Circular dichroism revealed a primarily (73%) helical structure of minimal stability ( =32°C) but reversibly denatured. Limited proteolysis (LP) and chemical modification identified the N-terminal 2/3 of the protein as dynamic and accessible, whereas size exclusion chromatography (SEC) confirmed three homo-oligomeric species. SEC coupled to chemical crosslinking characterized the primary species as dimeric, a secondary hexameric species, and a higher order aggregate/polymer. Fluorescence polarization using intrinsic tryptophan fluorescence contextualized the anisotropy value for the SIKE dimer (molecular weight 51.8 kDa) among proteins of known structure, bovine serum albumin (BSA; 66 kDa), and glutamate dehydrogenase (GDH; 332 kDa). Radii of gyration for BSA and GDH provided exclusionary values for SIKE tertiary and dimeric quaternary models that otherwise conformed to secondary structure, LP, and modification data. Dimeric quaternary models were further culled using acrylamide quenching data of SIKE's single tryptophan that showed a single, protected environment. The low cooperativity of folding and regions of dynamic and potentially disordered structure advance the hypothesis that SIKE forms a conformational ensemble of native states that accommodate SIKE's interactions with multiple, distinct protein-binding partners.