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Journal Journal of Pain Research

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Published: 18 January 2019
Journal of Pain Research; doi:10.2147/jpr

Abstract:An international, peer reviewed, open access, online journal that welcomes laboratory and clinical findings in the fields of pain research and the prevention and management of pain. Original research, reviews, symposium reports, hypothesis formation and commentaries are all considered for publication.
Jan M Keppel Hesselink, David J Kopsky, Arun K Bhaskar
Journal of Pain Research, Volume 12, pp 345-352; doi:10.2147/jpr.s180792

Abstract:Ethical justification of single-blind and double-blind placebo-controlled response tests in neuropathic pain and N-of-1 treatment paradigm in clinical settings Jan M Keppel Hesselink,1 David J Kopsky,2 Arun K Bhaskar3 1Institute for Neuropathic Pain, Bosch en Duin, The Netherlands; 2Institute for Neuropathic Pain, Amsterdam, The Netherlands; 3Pain Management Centre, Charing Cross Hospital Imperial Healthcare NHS Trust, London, UK At our center in the Netherlands, patients, who very often are treatment resistant to the analgesics recommended in the guidelines, suffering from symmetrical peripheral neuropathic pain are treated exclusively. We have developed a number of compounded topical formulations containing classical co-analgesics such as ketamine, baclofen, amitriptyline, and phenytoin for the treatment of neuropathic pain in treatment-resistant patients. In order to identify putative responders and exclude an (initial) placebo-response, we developed single-blind and double-blind placebo-controlled response tests. The test can be performed when the patient has a symmetrical polyneuropathy with a pain score difference of not more than 1 point on the 11-point numerical rating scale (NRS) between bilateral pain areas. On one area (eg, left foot) the placebo cream and on the other area (eg, right foot) the active cream will be applied. Within a time frame of 30 minutes, patients are considered responders if they rate a pain difference of at least 2 points on the NRS between the bilateral areas on which the active cream and placebo cream are applied. Response tests can be easily conducted during the first consultation. In this paper, we explore the ethical context of using a placebo in clinical practice in a single-blind and double-blind fashion to improve and individualize treatment of neuropathic pain outside a context of a formal clinical trial. Keywords: ethics, trial, topical,treatment, enrichment
Ying-Shuang Chang, Hung-Wei Kan, Yu-Lin Hsieh
Journal of Pain Research, Volume 12, pp 317-326; doi:10.2147/jpr.s186699

Abstract:Activating transcription factor 3 modulates protein kinase C epsilon activation in diabetic peripheral neuropathy Ying-Shuang Chang,1 Hung-Wei Kan,2 Yu-Lin Hsieh1,3 1Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 2Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan; 3Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan Background: Skin denervation that develops in patients with diabetes mellitus as a neuropathic manifestation is known as diabetic peripheral neuropathy (DPN). Skin denervation is parallel to neuronal injuries that alter intracellular signaling. To date, the correlation between nerve injury and the activation of intracellular responses to neuropathic manifestations has not been elucidated; specifically, whether activating transcription factor 3 (ATF3) is responsible for neuronal injury and a critical molecule that modulates the activation of intracellular protein kinase C epsilon (p-PKCε) and pain development in DPN is a crucial question. Methods: To address, ATF3 knockout (atf3−/− group, C57/B6 genetic background) and wild-type mice (atf3+/+ group) received a single dose of streptozotocin (200 mg/kg) to generate a mouse model of DPN. Results: Both atf3+/+ and atf3−/− mice exhibited hyperglycemia and the same pathology of skin denervation at posttreatment month 2, but only atf3+/+ mice developed thermal hyperalgesia (P<0.001) and mechanical allodynia (P=0.002). The atf3+/+ group, but not the atf3−/− group, had preferential ATF3 upregulation on p-PKCε(+) neurons with a ratio of 37.7%±6.1% in p-PKCε(+):ATF3(+) neurons (P<0.001). In addition, B-cell lymphoma-extra large (Bcl-XL), an antiapoptotic Bcl2 family protein, exhibited parallel patterns to p-PKCε (ie, Bcl-XL upregulation was reversed in atf3−/− mice). These two molecules were colocalized and increased by approximately two-fold in the atf3+/+ group compared with the atf3−/− group (30.0%±3.4% vs 13.7% ± 6.2%, P=0.003). Furthermore, linear analysis results showed that the densities of p-PKCε and Bcl-XL had a reverse linear relationship with the degrees of thermal hyperalgesia and mechanical allodynia. Conclusion: Collectively, this report suggested that ATF3 is a critical upstream molecule that modulates p-PKCε and Bcl-XL expression, which consequently mediated the development of neuropathic manifestation in DPN. Keywords: activating transcription factor 3, diabetic peripheral neuropathy, protein kinase C epsilon, PKCε, neuropathic pain, B-cell lymphoma-extra large, Bcl-XL
Margarita Udall, Ian Kudel, Joseph C Cappelleri, Alesia Sadosky, Kristen King-Concialdi, Bruce Parsons, Patrick Hlavacek, Markay Hopps, P Arline Salomon, Marco D DiBonaventura, et al.
Journal of Pain Research, Volume 12, pp 243-253; doi:10.2147/jpr.s160504

Abstract:Epidemiology of physician-diagnosed neuropathic pain in Brazil Margarita Udall,1 Ian Kudel,2 Joseph C Cappelleri,3 Alesia Sadosky,1 Kristen King-Concialdi,2 Bruce Parsons,1 Patrick Hlavacek,1 Markay Hopps,1 P Arline Salomon,4 Marco DiBonventura,2 Patricia Clark,5,6 João Batista Santos Garcia7 1Pfizer Inc, New York, NY, USA; 2Health Outcomes Practice, Kantar Health, New York, NY, USA; 3Pfizer Inc, Groton, CT, USA; 4Pfizer Inc, Bosques de las Lomas, Mexico; 5Clinical Epidemiology Unit, Hospital Infantil de México Federico Gómez, Mexico City, Mexico; 6Faculty of Medicine UNAM, Mexico City, Mexico; 7Pain and Palliative Care Department, Federal University of Maranhão, Maranhão, Brazil Objectives: Estimate the prevalence of neuropathic pain (NeP) among chronic pain patients attending Brazilian hospitals and pain clinics in São Paulo, Ceara, and Bahia and explore clinical characteristics by subtypes: painful diabetic peripheral neuropathy (pDPN), central neuropathic pain (CNP), chronic low back pain with a neuropathic component (CLBP-NeP), postherpetic neuralgia (PHN), post-traumatic neuropathic pain (PTN), and post-surgical neuropathic pain (PSN).Methods: Physicians screened patients reporting chronic pain for ≥3 months (n=2,118) for probable NeP, using the Douleur Neuropathique 4 questionnaire and physician assessment, and reported their NeP subtype(s), symptoms, and medications. Identified NeP patients completed a questionnaire including treatment experiences, quality of life EuroQol 5 Dimensions [EQ-5D]), pain severity and interference (Brief Pain Inventory [BPI]), and Work Productivity and Activity Impairment scales. Descriptive analyses were performed by NeP subtype.Results: The prevalence of probable NeP was 14.5% (n=307). NeP patients were mostly female (80.5%), middle-aged (mean [M]=52.5, SD=13.9), and Pardo (44.3%). Of those diagnosed with an NeP subtype (n=209), the largest proportions were CLBP-NeP (36.8%), followed by pDPN (18.7%), CNP (17.7%), PTN (17.2%), PSN (13.4%), and PHN (3.3%). Across subtypes, the most widely reported symptoms were numbness (range: 62.2%–89.7%) and hyperalgesia (range: 32.1%–76.9%) and the most commonly prescribed pain analgesics were NSAID (range: 18.2%–57.1%), opioids (range: 0.0%–39.3%), and antiepileptics (range: 18.2%–57.1%). PTN and PSN patients reported the least favorable EQ-5D index scores (M=0.42, SD=0.19) and BPI-Pain Severity scores (M=7.0, SD=1.9), respectively. Those diagnosed with CNP had the least favorable BPI-Pain Interference scores (M=6.0, SD=2.7). Patients with PHN reported the least impairment based on EQ-5D index scores (M=0.60, SD=0.04). Those with pDPN had the most favorable BPI scores (BPI-Pain Severity: M=4.6, SD=2.3; BPI-Pain Interference: M=4.7, SD=2.7).Conclusion: Evaluation of chronic pain patients in Brazil yielded a 14.5% probable NeP prevalence. NSAIDs and opioids were commonly used, and there was a high incidence of NeP-related symptoms with varying levels...
Ian Kudel, Markay Hopps, Joseph C Cappelleri, Alesia Sadosky, Kristen King-Concialdi, Ryan Liebert, Bruce Parsons, Patrick Hlavacek, Andrea H Alexander, Marco D DiBonaventura, et al.
Journal of Pain Research, Volume 12, pp 255-268; doi:10.2147/jpr.s160513

Abstract:Characteristics of patients with neuropathic pain syndromes screened by the painDETECT questionnaire and diagnosed by physician exam Ian Kudel,1 Markay Hopps,2 Joseph C Cappelleri,3 Alesia Sadosky,2 Kristen King-Concialdi,1 Ryan Liebert,1 Bruce Parsons,2 Patrick Hlavacek,2 Andrea H Alexander,2 Marco DiBonaventura,4 John D Markman,5 John T Farrar,6 Brett R Stacey7 1Health Outcomes Practice, Kantar Health, New York, NY, USA; 2Pfizer Inc, New York, NY, USA; 3Pfizer Inc, Groton, CT, USA; 4Pfizer Inc, New York, NY, USA; 5University of Rochester Medical Center School of Medicine and Dentistry, Rochester, NY, USA; 6Department of Biostatistics and Epidemiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 7UW Center for Pain Relief, University of Washington, Seattle, WA, USA Background: The aim of this study was to identify the clinical characteristics, treatment usage, and health outcomes of US adults diagnosed with neuropathic pain (NeP) by experienced physicians. Methods: Adults with scores exceeding the threshold for probable NeP (painDETECT ≥19) and diagnosed with NeP by a qualified physician completed a questionnaire that included comorbid conditions, pain symptoms and experiences, medication use, health status (3-level EuroQol 5 Dimensions (EQ-5D-3L]: health utilities index and visual analog scale), pain severity and interference with functioning (Brief Pain Inventory), and work and activity impairment (Work Productivity and Activity Impairment questionnaire). Descriptive analyses were performed for each NeP subtype. Results: Participants (n=295) were predominantly female (64.4%), middle-aged (53.9%), and white (51.5%). Chronic low back pain was the most frequently diagnosed major NeP syndrome (n=166), followed by diabetic peripheral neuropathy (n=58), post-trauma neuropathy (n=47), post-surgical neuropathy (n=28), and central NeP (n=23). An additional 45 participants were diagnosed, but did not meet the criteria for the aforementioned subtypes. Participants could be diagnosed with multiple subtypes. Across each NeP subtype, patients reported high rates of comorbid disease, including arthritis (range: 39.1%–64.3%) and high blood pressure (range: 26.1%–69.0%), as well as symptomology that included numbness (range: 68.1%–91.4%) and changes in muscular strength (range: 24.1%–65.2%). The majority of patients reported back pain (range: 77.8%–95.7%) and arthritis/joint pain (range: 68.1%–78.6%). The most commonly reported types of NeP pain medication were non-steroidal anti-inflammatory drugs (range: 43.1%–70.2%), weak opioids (range: 22.2%–39.3%), and strong opioids (range: 8.7%–28.6%). All six NeP groups generally reported similar levels of dysfunction on all self-report measures. The most notable finding was that the EuroQol-5D-3L health utilities index scores for each of the six groups were lower than the US norms by a clinically important amount. Conclusion: These exploratory findings...
Seyed Hamid Reza Faiz, Nader D. Nader, Soraya Niknejadi, Sina Davari-Farid, Geoffrey G. Hobika, Poupak Rahimzadeh
Journal of Pain Research, Volume 12, pp 201-207; doi:10.2147/jpr.s179506

Abstract:A clinical trial comparing ultrasound-guided ilioinguinal/iliohypogastric nerve block to transversus abdominis plane block for analgesia following open inguinal hernia repair Seyed Hamid Reza Faiz,1 Nader D Nader,2 Soraya Niknejadi,1 Sina Davari-Farid,2 Geoffrey G Hobika,2 Poupak Rahimzadeh3 1Department of Anesthesiology, Iran University of Medical Sciences, Tehran, Iran; 2Department of Anesthesiology, University at Buffalo, Buffalo, NY, USA; 3Pain Research Center, Iran University of Medical Sciences, Tehran, Iran Objective: To compare the efficacy of ilioinguinal/iliohypogastric (IINB) nerve block to transversus abdominis plane (TAP) block in controlling incisional pain after open inguinal hernia repair. Patients and methods: This was a prospective randomized clinical trial of 90 patients who received either IINB (N=45) or TAP block (N=45) using 0.2% bupivacaine 15 mL under ultrasound (US) guidance based on a random assignment in the postanesthesia care unit after having an open repair of inguinal hernia. Numeric Rating Scale (NRS) scores were recorded immediately following, 4, 8, 12, and 24 hours after completion of the block. NRS scores at rest and during movement were recorded 24, 36, and 48 hours after surgery. Analgesic satisfaction level was also evaluated by a Likert-based patient questionnaire. Results: NRS scores were lower in the IINB group compared to the TAP block group both at rest and during movement. The difference in dynamic pain scores was statistically significant (P=0.017). In addition, analgesic satisfaction was significantly greater in the IINB group than the TAP block group (mean score 2.43 vs 1.84, P=0.001). Postoperative opioid requirements did not differ between the two groups. Conclusion: This study demonstrated that compared to TAP block, local blockade of ilioinguinal and iliohypogastric nerves provides better pain control after open repair of inguinal hernia when both blocks were administered under US guidance. Greater satisfaction scores also reflected superior analgesia in patients receiving IINB. Keywords: US-guided nerve block, transversus abdominis plane, ilioinguinal, iliohypogastric nerve, inguinal hernia surgery
Kanta Kido, Shinichi Toda, Yuki Shindo, Hitoshi Miyashita, Shigekazu Sugino, Eiji Masaki
Journal of Pain Research, Volume 12, pp 377-385; doi:10.2147/jpr.s177098

Abstract:Effects of low-dose ketamine infusion on remifentanil-induced acute opioid tolerance and the inflammatory response in patients undergoing orthognathic surgery
Mikito Kawamata, Masako Iseki, Mamoru Kawakami, Shoji Yabuki, Takuma Sasaki, Mitsuhiro Ishida, Atsushi Nishiyori, Hideaki Hida, Shin-Ichi Kikuchi
Journal of Pain Research, Volume 12, pp 363-375; doi:10.2147/jpr.s179110

Abstract:Efficacy and safety of controlled-release oxycodone for the management of moderate-to-severe chronic low back pain in Japan: results of an enriched enrollment randomized withdrawal study followed by an open-label extension study
Jianda Xu, Yuxing Qu, Huan Li, Tao Jiang, Chong Zheng, Bin Wang, Pengfei Shen
Journal of Pain Research, Volume 12, pp 417-422; doi:10.2147/jpr.s178413

Abstract:Effect of ketorolac in intra-articular injection analgesia for postoperative pain in patients undergoing shoulder arthroscopy: a pilot-controlled clinical study
Yue Zhou, Hong Dai, Juan Long, Xin-Guo Kang, Chun-Jing He
Journal of Pain Research, Volume 12, pp 387-394; doi:10.2147/jpr.s177585

Abstract:Effects of extracorporeal shock waves on neuralgia in diabetic rats
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