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https://www.readbyqxmd.com/read/28324649/sulfonamides-as-selective-nav1-7-inhibitors-optimizing-potency-pharmacokinetics-and-metabolic-properties-to-obtain-atropisomeric-quinolinone-am-0466-that-affords-robust-in-vivo-activity
#1
Russell F Graceffa, Alessandro A Boezio, Jessica Able, Steven Altmann, Loren M Berry, Christiane M Boezio, John R Butler, Margaret Y Chu-Moyer, Melanie Cooke, Erin F DiMauro, Thomas A Dineen, Elma Feric Bojic, Robert S Foti, Robert T Fremeau, Angel Guzman-Perez, Hua Gao, Hakan Gunaydin, Hongbing Huang, Liyue Huang, Christopher Ilch, Michael Jarosh, Thomas Kornecook, Charles R Kreiman, Daniel S La, Joseph Ligutti, Benjamin Charles Milgram, Min-Hwa Jasmine Lin, Isaac E Marx, Hanh Nho Nguyen, Emily A Peterson, Gwen Rescourio, John Roberts, Laurie B Schenkel, Roman Shimanovich, Brian Andrew Sparling, John Stellwagen, Kristin Taborn, Karina R Vaida, Jean Wang, John T S Yeoman, Violeta L Yu, Dawn Zhu, Bryan D Moyer, Matthew M Weiss
Due to its strong genetic validation, NaV1.7 has attracted significant interest as a target for the treatment of pain. We have previously reported on a number of structurally distinct bicyclic heteroarylsulfonamides as NaV1.7 inhibitors that demonstrate high levels of selectivity over other NaV isoforms. Herein, we report the discovery and optimization of a novel series of atropisomeric quinolinone sulfonamide inhibitors of NaV1.7, which demonstrate nanomolar inhibition of NaV1.7 and exhibit high levels of selectivity over other sodium channel isoforms...
March 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28323713/efficacy-of-poly-d-l-lactic-acid-co-glycolic-acid-poly-ethylene-glycol-poly-d-l-lactic-acid-co-glycolic-acid-thermogel-as-a-barrier-to-prevent-spinal-epidural-fibrosis-in-a-postlaminectomy-rat-model
#2
Xiangqian Li, Lin Chen, Hong Lin, Luping Cao, Ji'an Cheng, Jian Dong, Lin Yu, Jiandong Ding
STUDY DESIGN: Experimental animal study. OBJECTIVE: The authors conducted a study to determine the efficacy and safety of the poly(D,L-lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(D,L-lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) thermogel to prevent peridural fibrosis in an adult rat laminectomy model. SUMMARY OF BACKGROUND DATA: Peridural fibrosis often occurs after spinal laminectomy. It might cause persistent back and/or leg pain postoperatively and make a reoperation more difficult and dangerous...
April 2017: Clinical Spine Surgery
https://www.readbyqxmd.com/read/28323703/biomechanical-effects-of-human-lumbar-discography-in-vitro-experiments-and-their-finite-element-validation
#3
Kristen E Lipscomb, Nesrin Sarigul-Klijn, Eric Klineberg, Vivek Mohan
STUDY DESIGN: An experimental and computational finite element analysis of human lumbar spine discography and its resulting effects on disk biomechanics. OBJECTIVE: To characterize the changes in stress and displacement of the human lumbar spine disks after puncture due to discography. SUMMARY OF BACKGROUND DATA: Discography of the intervertebral disk (IVD) may be used to diagnose pathology of the disk and determine whether it may be a source for chronic back pain...
April 2017: Clinical Spine Surgery
https://www.readbyqxmd.com/read/28323508/nefopam-hydrochloride-loaded-microspheres-for-post-operative-pain-management-synthesis-physicochemical-characterization-and-in-vivo-evaluation
#4
Neelam Sharma, Sandeep Arora, Jitender Madan
Once-daily oral dosage of nefopam hydrochloride loaded sustained release microspheres (NPH-MS) was investigated as novel therapeutic strategy for post-operative pain management. Microspheres were synthesized using poly-3-hydroxybutyrate and poly-(ɛ-caprolactone) by double emulsion solvent evaporation technique. NPH-MS were characterized through FTIR, PXRD and SEM. In-vitro drug release study revealed sustained behavior till 24 h. Haemolysis was <5% which signified haemocompatibility of formulation. ED50 in rat tail-flick anti-nociceptive test was found ∼18...
March 21, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28323403/discovery-of-potent-antiallodynic-agents-for-neuropathic-pain-targeting-p2x3-receptors
#5
Young-Hwan Jung, Yong-Chul Kim, Yeo Ok Kim, Hai Lin, Joong-Heui Cho, Jin-Hee Park, So-Deok Lee, Jinsu Bae, Koon Mook Kang, Yoon Gyoon Kim, Ae Nim Pae, Hyojin Ko, Chul-Seung Park, Myung Ha Yoon
Antagonism of the P2X3 receptor is one of the potential therapeutic strategies for the management of neuropathic pain because P2X3 receptors are predominantly localized on small to medium diameter C- and Aδ-fiber primary afferent neurons, which are related to the pain-sensing system. In this study, 5-hydroxy pyridine derivatives were designed, synthesized, and evaluated for their in vitro biological activities by two-electrode voltage clamp assay at hP2X3 receptors. Among the novel hP2X3 receptor antagonists, intrathecal treatment of compound 29 showed parallel efficacy with pregabalin (calcium channel modulator) and higher efficacy than AF353 (P2X3 receptor antagonist) in the evaluation of its antiallodynic effects in spinal nerve ligation rats...
March 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28320059/effects-of-treadmill-exercise-on-advanced-osteoarthritis-pain-in-rats
#6
Joshua Allen, Ian Imbert, Joshua Havelin, Terry Henderson, Glenn Stevenson, Lucy Liaw, Tamara King
OBJECTIVE: Exercise is commonly recommended for patients with osteoarthritis (OA) pain. However, whether exercise is beneficial in ameliorating persistent NSAID-resistant ongoing pain associated with advanced OA is unknown. METHODS: Rats treated with intra-articular monosodium iodoacetate (MIA) or saline underwent treadmill exercise or remained sedentary starting 10 days post-injection. Tactile sensory thresholds and weight bearing were assessed followed by radiographs at weekly intervals...
March 20, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28320048/dynamic-effects-of-depressive-symptoms-on-osteoarthritis-knee-pain
#7
Alan M Rathbun, Elizabeth A Stuart, Michelle Shardell, Michelle S Yau, Mona Baumgarten, Marc C Hochberg
OBJECTIVE: To estimate the dynamic causal effects of depressive symptoms on osteoarthritis (OA) knee pain. METHODS: Marginal structural models were used to examine dynamic associations between depressive symptoms and pain over 48 months among older adults (n=2,287) with radiographic knee OA (Kellgren-Lawrence grade=2 or 3) in the Osteoarthritis Initiative. Depressive symptoms at each annual visit were assessed (threshold = ≥ 16) using the Center for Epidemiological Studies Depression Scale...
March 20, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28320042/calcium-channel-modulation-as-a-target-in-chronic-pain-control
#8
REVIEW
Ryan Patel, Carlota Montagut-Bordas, Anthony H Dickenson
Neuropathic pain remains poorly treated for large numbers of patients and little progress has been made in developing novel classes of analgesics. To redress this issue, ziconotide (Prialt(TM) ) was developed and approved as a first in class synthetic version of ω-conotoxin MVIIA, a Cav 2.2 peptide blocker. Unfortunately, the impracticalities of intrathecal delivery, low therapeutic index and severe neurological side effects associated with ziconotide has restricted its use to exceptional circumstances. Ziconotide exhibits no state or use dependent block of Cav 2...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28319517/effects-of-a-lidocaine-loaded-poloxamer-alginate-cacl2-mixture-on-postoperative-pain-and-adhesion-in-a-rat-model-of-incisional-pain
#9
Geun Joo Choi, Hyun Kang, Min Eui Hong, Hwa Yong Shin, Chong Wha Baek, Yong Hun Jung, Younsuk Lee, Jeong Wook Kim, I L Kyu Park, Wan Jin Cho
BACKGROUND: Pain and adhesion are problematic issues after surgery. Lidocaine has analgesics and anti-inflammatory properties, and poloxamer/alginate/CaCl2 (PACM) is a known antiadhesive agent. We hypothesized that the novel combination of lidocaine as chemical barrier and PACM as physical barrier would be beneficial for both postoperative pain and adhesion. The purpose of this study was to investigate the effects of lidocaine-loaded PACM in a rat model of incisional pain. Primary outcome was to evaluate between-group differences for the mechanical withdrawal threshold (MWT) measured by von Frey filament in various concentrations of lidocaine-loaded PACM applied, PACM applied, and sham-operated groups...
March 17, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28319509/a-high-preoperative-pain-and-symptom-profile-predicts-worse-pain-outcomes-for-children-after-spine-fusion-surgery
#10
Terri Voepel-Lewis, Michelle S Caird, Alan R Tait, Shobha Malviya, Frances A Farley, Ying Li, Matthew D Abbott, Tara van Veen, Afton L Hassett, Daniel J Clauw
BACKGROUND: Preoperative pain predicts persistent pain after spine fusion, yet little is understood about the nature of that pain, related symptoms, and how these symptoms relate to postoperative pain outcomes. This prospective study examined children's baseline pain and symptom profiles and the association between a high symptom profile and postoperative outcomes. METHODS: Seventy children (aged 10-17 years) scheduled for correction of idiopathic scoliosis completed pain and symptom surveys during their preoperative visit (ie, pain intensity [0-10 numeric rating scores], a pediatric version of the 2011 fibromyalgia survey criteria [including pain locations and symptom severity scale], neuropathic pain symptoms [painDETECT], and Patient-Reported Outcome Measurement System measures of fatigue, depression, function, pain interference, and pain catastrophizing)...
March 17, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28319162/risk-of-acute-myocardial-infarction-in-patients-with-gastroesophageal-reflux-disease-a-nationwide-population-based-study
#11
Wei-Yi Lei, Jen-Hung Wang, Shu-Hui Wen, Chih-Hsun Yi, Jui-Sheng Hung, Tso-Tsai Liu, William C Orr, Chien-Lin Chen
OBJECTIVE: Gastroesophageal reflux disease (GERD) is a common disease which can cause troublesome symptoms and affect quality of life. In addition to esophageal complications, GERD may also be a risk factor for extra-esophageal complications. Both GERD and coronary artery disease (CAD) can cause chest pain and frequently co-exist. However, the association between GERD and acute myocardial infarction (AMI) remain unclear. The purpose of the study was to compare the incidence of acute myocardial infarction in GERD patients with an age-, gender-, and comorbidity matched population free of GERD...
2017: PloS One
https://www.readbyqxmd.com/read/28319133/effects-of-sudden-walking-perturbations-on-neuromuscular-reflex-activity-and-three-dimensional-motion-of-the-trunk-in-healthy-controls-and-back-pain-symptomatic-subjects
#12
Juliane Mueller, Tilman Engel, Steffen Mueller, Josefine Stoll, Heiner Baur, Frank Mayer
BACKGROUND: Back pain patients (BPP) show delayed muscle onset, increased co-contractions, and variability as response to quasi-static sudden trunk loading in comparison to healthy controls (H). However, it is unclear whether these results can validly be transferred to suddenly applied walking perturbations, an automated but more functional and complex movement pattern. There is an evident need to develop research-based strategies for the rehabilitation of back pain. Therefore, the investigation of differences in trunk stability between H and BPP in functional movements is of primary interest in order to define suitable intervention regimes...
2017: PloS One
https://www.readbyqxmd.com/read/28318987/a-clinical-evaluation-of-the-pharmacokinetics-and-pharmacodynamics-of-intravenous-alfaxalone-in-cyclodextrin-in-male-and-female-rats-following-a-loading-dose-and-constant-rate-infusion
#13
Kate L White, Stuart Paine, John Harris
OBJECTIVE: To characterise, as a clinical study, the pharmacokinetics and pharmacodynamics and describe the hypnotic effect of the neurosteroid alfaxalone (3α-hydroxy-5 α-pregnane-11, 20-dione) formulated with 2-hydroxypropyl-β-cyclodextrin in male and female rats. STUDY DESIGN: Prospective, experimental laboratory study. ANIMALS: A total of 12 (six male and six female) adult, aged-matched Sprague Dawley rats. METHODS: Surgery and instrumentation was performed under isoflurane anaesthesia in an oxygen/nitrous oxide mixture (1:2) and local anaesthetic infiltration...
February 1, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28318850/safety-and-efficacy-of-hyperosmolar-irrigation-solution-in-shoulder-arthroscopy
#14
Nicholas M Capito, James L Cook, Bernardo Yahuaca, Marie D Capito, Seth L Sherman, Matthew J Smith
BACKGROUND: A hyperosmolar irrigation solution has been reported to be safe and have potential benefits for use during shoulder arthroscopy in an animal model study. In this study, the clinical effects of a hyperosmolar solution were compared with a standard isotonic solution when used for shoulder arthroscopy. METHODS: A prospective, double-blind, randomized controlled trial was performed to compare isotonic (273 mOsm/L) and hyperosmolar (593 mOsm/L) irrigation solutions used for arthroscopic rotator cuff repair...
March 15, 2017: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/28318363/sexual-orientation-and-college-students-reasons-for-nonmedical-use-of-prescription-drugs
#15
Faedra R Dagirmanjian, Anne E McDaniel, Richard Shadick
BACKGROUND: Nonmedical use of prescription pain medications, sedatives, and stimulants is a well-documented problem among college students. Research has indicated that students who identify as lesbian, gay, or bisexual are at elevated risk. However, little is known about students' reasons for use. OBJECTIVES: (1) To replicate findings that sexual minority students report higher nonmedical use than heterosexual students, moving from a campus-specific to a multicampus sample and (2) to test for an association between sexual orientation and reasons for use...
March 20, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28318085/inflammatory-double-hit-model-of-temporomandibular-joint-disorder-with-elevated-ccl2-cxcl9-cxcl10-rantes-and-behavioural-hypersensitivity-in-tnfr1-r2-mice
#16
S L McIlwrath, R Nesemeier, F Ma, H S Oz, L Zhang, K N Westlund
BACKGROUND: Patients with temporomandibular joint disorders (TMD), reactive arthritis and rheumatoid arthritis often have combined etiology of hereditary and microenvironmental factors contributing to joint pain. Multiple clinical and animal studies indicate 'double-hit' inflammatory insults can cause chronic inflammation. The first inflammatory insult primes the immune system and subsequent insults elicit amplified responses. The present 'double hit' study produced a chronic orofacial pain model in mice with genetic deletion of both TNFα receptors (TNFR1/R2-/-), investigating the main nociceptive signalling pathways in comparisons to wild type mice...
March 20, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28318068/helicid-alleviates-pain-and-sleep-disturbances-in-a-neuropathic-pain-like-model-in-mice
#17
Meng-Qi Zhang, Tian-Xiao Wang, Rui Li, Zhi-Li Huang, Wu-Jian Han, Xiao-Chang Dai, Yi-Qun Wang
Natural helicid (4-formylphenyl-O-β-d-allopyranoside), a main active constituent from seeds of the Chinese herb Helicia nilagirica, has been reported to exert a sedative, analgesic and hypnotic effect, and is used clinically to treat neurasthenic syndrome, vascular headaches and trigeminal neuralgia. In the current study, mechanical allodynia tests, electroencephalograms, electromyogram recordings and c-Fos expression in neuropathic pain-like model mice of partial sciatic nerve ligation were used to investigate the effect of helicid on neuropathic pain and co-morbid insomnia...
March 20, 2017: Journal of Sleep Research
https://www.readbyqxmd.com/read/28316278/high-risk-obstetrical-call-center-a-model-for-regions-with-limited-access-to-care
#18
Sarah J Rhoads, Hari Eswaran, Christian E Lynch, Songthip T Ounpraseuth, Everett F Magann, Curtis L Lowery
PURPOSE: High-risk obstetrical care can be challenging for women in rural states with limited access. MATERIALS AND METHODS: Data were evaluated from 62,342 obstetrical calls from pregnant and postpartum patients within rural Arkansas to a nurse call center. Call center nurses provided triage using evidence-based guidelines to patients across the state. Data were extracted and analyzed using retrospective data collection and descriptive statistical methods. RESULTS: Women had an average maternal age of 28 years old, average weeks gestation was 27...
March 19, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28316166/-analgesic-effect-and-related-mechanism-of-peripheral-acupoints-electroacupuncture-on-superficial-partial-thickness-burn-rats
#19
X Sun, Z R Wei, Z Xiao
Objective: To observe the analgesic effect and related mechanism of peripheral acupoints electroacupuncture on superficial partial-thickness burn rats. Methods: Eighty SD rats were divided into sham injury group (SI), pure burn group (PB), electroacupuncture group (E), and sham electroacupuncture group (SE) according to the random number table, with 20 rats in each group. Right posterior leg of rats in group SI were sham injured, while superficial partial-thickness scald (hereinafter referred to as burn) model was reproduced on the right posterior leg of rats in the latter three groups...
March 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/28315479/biopsychosocial-influence-on-shoulder-pain-rationale-and-protocol-for-a-pre-clinical-trial
#20
Steven Z George, Roland Staud, Paul A Borsa, Samuel S Wu, Margaret R Wallace, Warren H Greenfield, Lauren N Mackie, Roger B Fillingim
BACKGROUND: Chronic musculoskeletal pain conditions are a prevalent and disabling problem. Preventing chronic musculoskeletal pain requires multifactorial treatment approaches that address its complex etiology. Prior cohort studies identified a high risk subgroup comprised of variation in COMT genotype and pain catastrophizing. This subgroup had increased chance of heightened pain responses (in a pre-clinical model) and higher 12month post-operatives pain intensity ratings (in a clinical model)...
March 14, 2017: Contemporary Clinical Trials
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