Sensory Function and Pain Experience in Arthritis, Complex Regional Pain Syndrome, Fibromyalgia Syndrome and Healthy Volunteers: A Cross-sectional Study Objectives: This study aimed to identify relationships between sensory function and pain in common pain conditions (Arthritis, Complex Regional Pain Syndrome (CRPS) and Fibromyalgia Syndrome (FMS)) and healthy participants. Sensory abnormalities are known to be concomitant with some types of chronic pain but comparison across pain conditions using existing research is difficult due to methodological differences. Pragmatic Quantitative Sensory Testing (QST) methods were used. Methods: Hot and cold sensitivity, light touch threshold (LTT), two-point discrimination (TPD) and pressure pain threshold (PPT) were assessed in 143 participants (n=37 Healthy, n=34 Arthritis, n=36 CRPS, n=36 FMS). Outcomes were assessed in the index (“affected” or right) and contralateral arm. Participants also completed the Brief Pain Inventory and McGill Pain Questionnaire. Results: There were statistically significant differences between groups for all QST outcomes except TPD. Relative to healthy participants, FMS displayed heat hyperesthesia in both arms and cold hyperesthesia in the contralateral arm. CRPS demonstrated no changes in thermal sensitivity. Both CRPS and FMS exhibited bilateral pressure hyperalgesia. LTT hypoesthesia was observed bilaterally for CRPS but only in the contralateral arm for FMS. CRPS and FMS had pressure hyperalgesia in the index arm relative to Arthritis patients. There were no differences between Arthritis and Healthy participants for any QST outcome. In CRPS there were significant correlations between LTT and pain outcomes bilaterally. Discussion: People with FMS and CRPS demonstrate extensive sensory dysfunction. Arthritis patients had sensory profiles closer to healthy participants. LTT may provide a clinically relevant and accessible assessment for CRPS. Address for reprints: as above. Sources of support: C McCabe was funded by a National Institute for Health Research Career Development Fellowship (CDF/2009/02). This paper presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Acknowledgements: The research team would like to thank Lindsay Davies for her administrative support for the project. The authors declare no conflict of interest. Reprints: Shea Palmer, PhD, University of the West of England, Glenside Campus, Blackberry Hill, Bristol BS16 1DD (e-mail: Shea.Palmer@uwe.ac.uk). Received March 12, 2019 Received in revised form July 5, 2019 Accepted July 27, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Subgroup of Chronic Low Back Pain Patients with Central Sensitization Background: Our knowledge of central sensitization (CS) in chronic low back pain (CLBP) is limited. 2011 fibromyalgia criteria and severity scales (2011 FM survey) has been used to determine FM positive as a surrogate of CS. The major features of CS including widespread hyperalgesia and dysfunction of the descending inhibitory pathways can be identified by pressure pain threshold (PPT) and conditioned pain modulation (CPM) tests. The purpose of the study was to examine neurophysiological characteristics and psychosocial symptoms in a subgroup of FM positive CLBP compared to FM negative CLBP patients. Methods: 46 participants with CLBP and 22 healthy controls completed outcome measures of the 2011 FM survey, PPT and CPM tests, and psychosocial questionnaires. Differences between FM positive and FM negative CLBP participants on these measures and correlations were analyzed. Results: The 2011 FM survey identified 22 (48%) participants with CLBP as FM positive. FM positive CLBP participants showed lower PPT values of the thumbnail (P=0.011) and lower back (P=0.003), lower CPM values of the thumbnail (P=0.002), and more severe pain catastrophizing, anxiety and depression symptoms (P<0.05) than FM negative CLBP participants. The 2011 FM scores were significantly correlated with the PPT and CPM values of the thumbnail and with psychosocial symptoms (P<0.001). Discussion: Our findings suggest a subgroup of CLBP patients exhibiting with signs and symptoms of CS. Associations between subjective and objective CS measures indicate that the 2011 FM survey can be utilized to identify the presence of CS in CLBP in clinical practice. Author contributions: Study concept, design, and protocol development: KA, DC and NS. Data collection and statistical analyses: KA. Interpretation of the data and drafting of the manuscript: KA, JH and NS. Discussion of the results, revising the drafts and final approval of the manuscript: All authors. Conflict of interest disclosure and source of funding: The authors have no conflict of interest to declare. This work was partially supported by the T32 Program (T32HD057850; PI: Randolph Nudo) to Andrew D and J Vaughan and by the Department of Physical Therapy and Rehabilitation Science to NK Sharma. A Nicol has received research funding from National Institute of General Medical Sciences of the National Institutes of Health (NIH #K23GM123320) and served as a consultant for Heron Therapeutics and on an advisory board of Sandoz International. Reprints: Neena Sharma, PT, PhD, 3901 Rainbow Blvd, Kansas City, KS 66160 (e-mail: nsharma@kumc.edu). Received March 13, 2019 Received in revised form June 13, 2019 Accepted July 27, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Letter to the Editor in Response to “The Impact of Female Chronic Pelvic Pain Questionnaire (IF-CPPQ)”: A Validation Study No abstract available

Comparison of Effectiveness of Etoricoxib and Diclofenac On Pain and Perioperative Sequelae After Surgical Avulsion of Mandibular Third Molars: A Randomized, Controlled, Clinical Trial Objectives: The objective of this analysis was to compare the efficacy of etoricoxib and diclofenac in the management of perioperative sequelae following impacted mandibular third molar surgery. Materials and Methods: Ninety-seven patients who needed surgical avulsion of an impacted mandibular third molar were chosen for the study. All patients were randomly allocated to receive one of the following treatments, twice a day for 5 days after surgery: placebo (n=33), diclofenac (n=32), or etoricoxib (n=32). The primary outcome evaluated was postoperative pain, recorded by each patient and evaluated using the visual analogue scale (VAS) score. The secondary outcomes chosen were, compared to preoperative ones, changes in postoperative swelling and maximum mouth opening. Results: Compared to placebo, treatment with etoricoxib and diclofenac determined an enhancement in the primary outcome. Furthermore, when compared to the other groups, patients which undergone etoricoxib presented a significant median reduction in postoperative pain at 2 hours (P<0.001), 12 hours (P=0.025), and at 48 hours (P=0.018) after surgery. Moreover, the linear regression analysis showed that diclofenac and etoricoxib determined a significant influence on VAS at 2,6,12,24,48 hours and at 10 days after surgery. There were no differences in swelling and maximum mouth opening values between groups. Discussion: This study demonstrated that both treatment were effective. However, treatment with etoricoxib determine a better decrease in the incidence and severity of postoperative pain following third molar surgery compared to diclofenac and placebo. Sources of support: This work was carried out with funding from the Department Department of General Surgery and Surgical-Medical Specialties of the University of Catania. Funding: This work was carried out with funding from the Department of Biomedical, Odontostomatological Sciences and of Morphological and Functional Images of the University of Messina. Ethical approval: This study followed the Declaration of Helsinki on medical protocol. The Institutional Review Board of the University of Messina approved the study protocol (#35-17). Patient consent: Written informed consent was obtained from the patient for publication. Author Contributions: G.I. and G.M. conceived the idea of the work, and planned and performed the experimental procedures. AA performed the statistical analysis. G.I., M.M., D.D., E.P. and E.R. analysed and summarized the experimental results. G.I. wrote the paper. Competing interests: The authors declare that they have no conflict of interest or other benefits in the manuscript. Reprints: Gaetano Isola, DDS, PhD, Pg. Oral Surg., Department of General Surgery and Surgical-Medical Specialties, University of Catania. Via Plebiscito 628, 15a Building, Catania, 95124 Italy (e-mail: gaetano.isola@unict.it). Received January 24, 2019 Received in revised form June 25, 2019 Accepted July 14, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Efficacy and Safety of Low-dose Codeine Containing Combination Analgesics for Pain: Systematic Review and Meta-analysis Objective: To investigate the efficacy and safety of combination analgesic products containing low-dose codeine (up to 30▒mg per dose) for pain. Methods: We used electronic databases to identify eligible placebo-controlled RCTs. Two authors extracted data and assessed risk of bias. Data were pooled using a random effects model with strength of evidence assessed using GRADE. The primary outcome was immediate pain relief (3-hours post-administration) on a 0-100 pain scale. Results: Ten RCTs were eligible. There is low quality evidence (4 RCTs, n=211 participants) that a single dose of a combination analgesic product (with an NSAID) containing low-dose codeine (15▒mg to 30▒mg) provides small pain relief for acute dental pain; mean difference (MD) [95% CI] −12.7 [−18.5, −6.9] and moderate quality evidence (1 RCT, n=93) of small pain relief for post-episiotomy pain and orthopaedic surgery pain; MD [95% CI] −10.0 [−19.0, −1.0] and −11.0 [−20.7, −1.3] respectively. There is low quality evidence (1 RCT, n=80) that a multiple dose regimen provides small pain relief for acute pain following photorefractive keratectomy; MD [95% CI] −16.0 [−24.5, −7.5] and moderate quality evidence of moderate pain relief for certain chronic pain conditions; −19.0 [−31.2, −6.8] for hip osteoarthritis and −26.0 [−44.5, −7.5] for temporomandibular joint pain. Two studies reported a higher incidence of drowsiness in the treatment group compared with the placebo group; RR [95%CI] 8.50 [1.96, 36.8] to 19.3 [1.2, 306.5]. Discussion: There is low to moderate level evidence that combination analgesic products containing low-dose codeine provide small to moderate pain relief for acute nociceptive and chronic pain conditions in the immediate short term with limited trial data on use beyond 24-hours. Further research examining regular use of these medicines is needed with more emphasis on measuring potential harmful effects. Funding: This research was funded by the Therapeutic Goods Administration, Australia. Funding/Support: This research was supported by the Therapeutic Goods Administration, Australia. The authors declare no conflict of interest. Reprints: Christina Abdel Shaheed, PhD, Faculty of Medicine and Health, Sydney School of Public Health, University of Sydney, Sydney, Australia, Level 10 North, King George V Building, Royal Prince Alfred Hospital (C39) PO Box 179, MISSENDEN ROAD NSW 2050 (e-mail: Christina.Abdelshaheed@sydney.edu.au). Received August 31, 2018 Received in revised form June 23, 2019 Accepted June 30, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Brief Cognitive Behavioral Therapy for Chronic Pain: Results from a Clinical Demonstration Project in Primary Care Behavioral Health Objectives: Although cognitive behavioral therapy is an effective intervention for chronic pain, it is a lengthy treatment typically applied only in specialty care settings. The aim of this project was to collect preliminary effectiveness data for Brief Cognitive Behavioral Therapy for Chronic Pain (Brief CBT-CP), an abbreviated, modular form of treatment designed for use in primary care. Methods: A clinical demonstration project was conducted in which Brief CBT-CP was delivered to primary care patients by 22 integrated care providers practicing in the Primary Care Behavioral Health model of Veterans Health Administration primary care clinics. Brief measures were used at each appointment to collect patient reported clinical outcomes. Results: One hundred eighteen patients provided sufficient data for analysis (male, 75%; mean age, 51.4▒y). Multi-level modeling suggested that a composite measure of pain intensity and functional limitations showed statistically significant improvements by the third appointment (Cohen’s D=0.65). Pain-related self-efficacy outcomes showed a similar pattern of results but of smaller effect size (Cohen’s D=0.22). Exploratory analysis identified that Brief CBT-CP modules addressing psychoeducation and goal setting, pacing, and relaxation training were associated with the most significant gains in treatment outcomes. Discussion: These findings provide early support for the effectiveness of Brief CBT-CP when delivered by providers in every day Primary Care Behavioral Health settings. Results are discussed in relation to the need for additional research regarding the potential value of employing safe, population-based, non-pharmacologic approaches to pain management in primary care. This material is the result of work supported with resources and the use of facilities at the VA Center for Integrated Healthcare at the VA Western New York Healthcare System. The information provided in this study does not represent the views of the Department of Veterans Affairs or the United States Government. Disclosure and Acknowledgements: There are no known conflicts of interest for reasons financial or otherwise, no known competing interests, and no companies or products are being featured in this research. Reprints: Gregory P. Beehler, PhD, MA, VA Center for Integrated Healthcare (116N), VA WNY Healthcare System, 3495 Bailey Ave, Buffalo, NY 14215 (e-mail: gregory.beehler@va.gov). Received January 22, 2019 Received in revised form June 26, 2019 Accepted July 2, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Letter to the Editor for Article Titled Dexmedetomidine as an Adjuvant to Local Anesthetics in Transversus Abdominis Plane Block: A Systematic Review and Meta-analysis No abstract available

Non-specific Low Back Pain: Inflammatory Profiles of Patients with Acute and Chronic Pain Background: The pathogenesis of low back pain (LBP) remains unclear. However, recent studies suggest that the inflammatory response may be inherent in spinal pain. Purpose: To discern inflammatory profiles in patients with non-specific acute and chronic low back pain (LBP) in relation to those in asymptomatic subjects. Methods: Peripheral blood samples were obtained from asymptomatic subjects and patients with non-specific acute and chronic LBP reporting a minimum pain score of 3 on a 10-point visual analogue scale (VAS). The levels of in vitro production of pro-inflammatory (TNFα, IL-1β, IL-6, IL-2, IFN[Latin Small Letter Gamma]) and anti-inflammatory (IL-1 RA, sTNFR2 and IL-10) mediators were determined by specific immunoassays. Results: The mean VAS scores were comparable between the acute and chronic LBP patient groups. Compared to asymptomatic subjects, the production of TNFα, IL-1β, IL-6 and their ratios to IL-10 levels were significantly elevated in both patient groups (P=0.0001-0.003). In acute LBP group, the ratio of IL-2: IL-10 was also significantly increased (P=0.02). In contrast, the production of IFN[Latin Small Letter Gamma] was significantly reduced compared with the other study groups (P=0.005-0.01), nevertheless, it was positively correlated (P=0.006) with pain scores. In chronic LBP patients, the production of TNFα, IL-1RA and sTNFR2 was significantly increased (P=0.001-0.03) in comparison with the control and acute LBP groups, and TNFα and IL-1β levels were positively correlated (P<0.001) with VAS scores. Conclusion: The inflammatory profiles of patients with acute and chronic LBP are distinct. Nonetheless, in both patient groups, an imbalance between pro- and anti-inflammatory mediator levels favors the production of pro-inflammatory components. ACKNOWLEDGMENTS: We wish to express our appreciation and gratitude to Dr. A. Teitelbaum for performing phlebotomy. The excellent technical assistance of Ms. A. Corless is deeply appreciated. Conflict of Interest and Source of Funding: All authors declare that they have no conflict of interest to disclose regarding this manuscript. The study was supported by funds from Canadian Memorial Chiropractic College. Reprints: H. Stephen Injeyan, PhD, DC, Canadian Memorial Chiropractic College, 6100 Leslie Street, Toronto, Ontario, M2H 3J1, Canada (e-mail: sinjeyan@cmcc.ca). Received December 27, 2018 Received in revised form May 15, 2019 Accepted June 14, 2019 This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/ Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Validity of the Budapest Criteria for Post-stroke Complex Regional Pain Syndrome Objectives: Complex regional pain syndrome-1 (CRPS-1) is a chronic neuropathic disorder, and post-stroke CRPS (PS-CRPS) is not a rare complication. There is a lack of study implementing the Budapest criteria for PS-CRPS diagnosis. Thus, the present study investigated the validity of the Budapest criteria for PS-CRPS diagnosis and assessed the PS-CRPS-related factors in stroke patients with an affected upper extremity. Methods: The study included 72 patients with first-ever stroke resulting in hemiplegia. The prevalence of PS-CRPS and diagnostic validity were compared among the Budapest clinical criteria, Budapest research criteria, modified Budapest criteria (removal of the motor factor from the motor/trophic category), and International Association for the Study of Pain (IASP) criteria in patients diagnosed with PS-CRPS according to the Budapest clinical criteria. Results: PS-CRPS was diagnosed in 6 (8.3%), 1 (1.4%), 6 (8.3%), and 11 patients (15.3%) according to the Budapest clinical criteria, Budapest research criteria, modified Budapest criteria, and IASP criteria, respectively. The Budapest criteria and IASP criteria had sensitivities of 0.99 and 1.00, respectively, and specificities of 0.68 and 0.41, respectively, for PS-CRPS diagnosis. There were no differences in risk factors between PS-CRPS patients and non-PS-CRPS patients when the diagnosis was based on the Budapest clinical criteria. However, there were differences in muscle strength and Brunnstrom stage between PS-CRPS patients and non-PS-CRPS patients when the diagnosis was based on the IASP criteria. Discussion: Our findings indicate that the diagnostic validity of the current Budapest clinical criteria for PS-CRPS is low. Thus, the current Budapest criteria might not be appropriate for PS-CRPS diagnosis. Acknowledgments: We would like to thank Editage (http://www.editage.co.kr) for English language editing. There are no conflicts of interest. Conflicts of Interest and Source of Funding: We would like to thank Editage (http://www.editage.co.kr) for English language editing. Reprints: Joon-Ho Shin, MD, MS, Department of Rehabilitation Medicine, National Rehabilitation Center, 58, Samgaksan-ro, Gangbuk-gu, Seoul, 01022, Republic of Korea (e-mail: asfreelyas@gmail.com). Received January 17, 2019 Accepted June 17, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Mandatory Pain Assessment in a Pediatric Emergency Department: Failure or Success? A Retrospective Study Objective: Pain control is a priority in patient evaluation. Despite the proliferation of guidelines, pain is still under assessed and undertreated, especially in children. To improve efficiency and to adhere to best medical practice, our triage software was upgraded; it included mandatory pain scoring for the admission of a child to the pediatric emergency service, thereby limiting the chances of overlooking a child experiencing pain. We conducted this study to verify the effect of routine versus mandatory pain scoring on pain management under the hypothesis that mandatory pain assessment would improve re-evaluation and pain treatment. Methods: This retrospective case-control study was conducted in our Pediatric Emergency Department. We collected data regarding pain assessment and reassessment at triage and during the entire stay in the ED, as well as the drugs eventually administered. We reviewed the charts of 1274 patients admitted with the older triage software and of 1262 patients admitted with the newer triage software (intervention group). Results: Pain was evaluated significantly more frequently in the intervention group at triage, during medical evaluation, and at discharge. In the intervention group, a smaller percentage of patients were treated for pain at both triage and during their stay in the ED (P=0.078 and P=0.048). Pain re-assessment resulted worse in the intervention group (P<<0.001). Discussion: Mandatory pain assessment improved the pain evaluation rate. This did not, however, translate into better treatment and management of pain in the pediatric emergency setting. No funding sources were provided for this study. DISCLOSURE: The authors declare no conflict of interest. Reprints: Federico Marzona, MD, University of Udine, Department of Medicine (DAME), “S. Maria della Misericordia” Academic Hospital, 33100, Udine, Italy (e-mail: federico.marzona@asuiud.sanita.fvg.it). Received December 11, 2018 Received in revised form June 4, 2019 Accepted June 24, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.