Neuromodulation as a Potential Disease-Modifying Therapy for Osteoarthritis.

PURPOSE OF REVIEW: The following review discusses the therapeutic potential of targeting the autonomic nervous system (ANS) for osteoarthritis (OA) treatment and encourages the field to consider the candidacy of bioelectronic medicine as a novel OA treatment strategy. RECENT FINDINGS: The study of OA pathogenesis has focused on changes occurring at the joint level. As such, treatments for OA have been aimed at the local joint environment, intending to resolve local inflammation and decrease pain. However, OA pathogenesis has shown to be more than joint wear and tear. Specifically, OA-related peripheral and central sensitization can prompt neuroplastic changes in the nervous system beyond the articular joint. These neuroplastic changes may alter physiologic systems, like the neuroimmune axis. In this way, OA and related comorbidities may share roots in the form of altered neuroimmune communication and autonomic dysfunction. ANS modulation may be able to modify OA pathogenesis or reduce the impact of OA comorbidities. Moreover, blocking chronic nociceptive drive from the joint may help to prevent maladaptive nervous system plasticity in OA.

Partial high frequency nerve block decreases neuropathic signaling following chronic sciatic nerve constriction injury.

Objective.High frequency (HF) block can quickly and reversibly stop nerve conduction. We hypothesized HF block at the sciatic nerve would minimize nociception by preventing neuropathic signals from reaching the central nervous system.Approach.Lewis rats were implanted with a constriction cuff and a distal cuff electrode around their right sciatic nerve. Tactile sensitivity was evaluated using the 50% paw withdrawal threshold (PWT) determined using Chaplan's method for von Frey monofilaments. Over the course of 49 d, the 50% PWT was measured (1) before HF block, (2) during HF block (50 kHz, 3Vpp), and (3) after HF block. Gait was observed and scored before and during block. At end point, HF block efficacy was directly evaluated using additional cuff electrodes to elicit and record compound neural action potentials across the HF blocking cuff.Main results.At days 7 and 14 d post-operation, tactile sensitivity was significantly lower during HF block compared to before and after block (p< 0.005). Additionally, an increase in gait disability was not visually observed during HF block.Significance.HF block can reduce tactile sensitivity in a limb with a neuropthic injury in a rapidly reversible fashion.

Innovations in Worksite Diagnosis of Urinary Tract Infections and the Occupational Health Nurse.

Occupational health nurses play a key role in evaluating innovative technologies that can aid in providing safe and rapid care and reduce lost work time. A nurse-led employee health clinic participated in a validation study of a novel pathogen detection technique developed by GeneCapture, Inc. Their proposed portable urinary tract infection (UTI) in vitro diagnostic test was challenged with discarded, deidentified urine samples from patients presenting with typical UTI symptoms collected at two university clinics and two multiphysician practices. GeneCapture's panel for this study was designed to rapidly identify the genetic signature of seven organisms: gram-negative Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa; gram-positive Enterococcus faecalis and Staphylococcus aureus; and fungal Candida species. The results from 40 clinical samples were in 95% agreement (90% specificity, 100% sensitivity) with traditional urine culture results from routine analysis. This successful occupational health nursing collaboration and validation study shows promise for point-of-care diagnoses and earlier treatment for workers with UTIs.

A novel zebrafish-based model of nociception.

Chronic pain affects the lives of millions yearly, but few new treatments are available. Due to decreasing budgets and increasing costs of preclinical research, alternatives are sought with high translatability and low cost. Here we demonstrate the utility of a zebrafish-based model of nociception to serve as a novel screening tool for analgesic drugs. Zebrafish swimming behavior was measured following administration of various algogens including histamine, cinnamaldehyde, mustard oil, acetic acid and complete Freund's adjuvant. All compounds reduce distance traveled, thought to be an expression of nociception. Additionally, the suppression of swimming was attenuated by administration of the common analgesic, morphine. Together these data provide support for the use of zebrafish as a cost-effective and translatable model of nociception.

Efficacy of Common Analgesics for Postsurgical Pain in Rats.

Each year, millions of rats undergo surgery for research purposes and receive analgesics to alleviate pain. We sought to evaluate the efficacy of common analgesics in tests of hot-plate nociception and postsurgical pain by using the Rat Grimace Scale. Rats received a single dose of one of several drug-dose combinations and were tested by using the hot-plate test (acute pain) or after laparotomy (with either prophylactic or intraoperative analgesic). The efficacy of analgesics for hot-plate pain was generally not predictive of efficacy for surgical pain. Carprofen and ketoprofen were rarely effective in any of the conditions tested. With the exception of the opioid buprenorphine, several of the drugs we tested required higher-than-recommended doses to alleviate pain. Taken together, our data suggest that current analgesic use frequently is insufficient, and many rats may experience significant postsurgical pain even when analgesics are used in commonly recommended doses.