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      Preventive Analgesic Efficacy of Nefopam in Acute and Chronic Pain After Breast Cancer Surgery : A Prospective, Double-Blind, and Randomized Trial

      research-article
      , MD, PhD, , MD, PhD, , MD, PhD, , MD, , MD, PhD, , MD
      Medicine
      Wolters Kluwer Health

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          Abstract

          Breast cancer surgery is known to cause severe acute postoperative pain, which can persist for a long time. We administered nefopam preventively to patients undergoing lumpectomy with axillary lymph node dissection or sentinel lymph node biopsy, and evaluated its efficacy on acute and chronic postoperative pain.

          Enrolled patients were assigned to the nefopam (n = 41) or the control (n = 42) group. Before initiating the operation, 20 mg of nefopam was given to the patients of the nefopam group, and normal saline was used in the control group. Ketorolac was given at the end of surgery, and meloxicam was prescribed in the postoperative period to all patients in both groups. Pain was assessed using a numerical rating scale (NRS), and the rescue analgesic drug was given when the NRS was >5. Implementation of postoperative chemotherapy, radiotherapy (RT), or hormone therapy was evaluated.

          The NRS of postoperative pain was significantly lower in the nefopam than in the control group in the postanesthetic care unit (4.5 ± 2.2 vs 5.7 ± 1.5, respectively; P = 0.01), at postoperative 6 h (3.0 ± 1.6 vs 4.5 ± 1.3, respectively; P < 0.001), and at postoperative 24 h (3.1 ± 1.1 vs 3.8 ± 1.5, respectively; P = 0.01) with reduced use of rescue analgesic drugs. Significantly fewer patients suffered from chronic postoperative pain in the nefopam than in the control group at postoperative 3 months (36.6% vs 59.5%, P = 0.04). Considering only the cohort without postoperative adjuvant RT, the difference in the proportion of patients reporting chronic pain increased (23.5% in the nefopam group vs 61.5% in the control group, P = 0.04).

          Preventive nefopam was helpful in reducing the acute postoperative pain, with reduced use of rescue analgesic drugs, and it contributed to reduced occurrence of chronic pain at postoperative 3 months after breast cancer surgery.

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          The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review.

          There is accumulating evidence to implicate the importance of N-methyl-D-aspartate (NMDA) receptors to the induction and maintenance of central sensitization during pain states. However, NMDA receptors may also mediate peripheral sensitization and visceral pain. NMDA receptors are composed of NR1, NR2 (A, B, C, and D), and NR3 (A and B) subunits, which determine the functional properties of native NMDA receptors. Among NMDA receptor subtypes, the NR2B subunit-containing receptors appear particularly important for nociception, thus leading to the possibility that NR2B-selective antagonists may be useful in the treatment of chronic pain.
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            Acute pain after thoracic surgery predicts long-term post-thoracotomy pain.

            Long-term pain is a common sequela of thoracotomy, occurring in approximately 50% of patients 2 years after thoracic surgery. Despite this alarming statistic, little is known about the factors responsible for the transition of acute to chronic pain. The aim of the present study is to identify predictors of long-term post-thoracotomy pain. Follow-up was for 1.5 years for patients who had participated in a prospective, randomized, controlled trial of preemptive, multimodal analgesia. Subjects were recruited from a tertiary care center. Thirty patients who had undergone lateral thoracotomy were followed up by telephone, administered a structured interview, and classified according to long-term pain status. Present pain status was measured by a verbal rating scale (VAS). Measures obtained within the first 48 h after surgery were compared between patients with and without pain 1.5 years later. These include VAS pain scores at rest and after movement, McGill Pain Questionnaire data, patient-controlled morphine consumption (mg), and pain thresholds to pressure applied to a rib contralateral to the thoracotomy incision. Fifty-two percent of patients reported long-term pain. Early postoperative pain was the only factor that significantly predicted long-term pain. Pain intensity 24 h after surgery, at rest, and after movement was significantly greater among patients who developed long-term pain compared with pain-free patients. A significant predictive relationship was also found at 24 and 48 h using the McGill Pain Questionnaire. Cumulative morphine was comparable for the two groups. Pain thresholds to pressure applied to a rib contralateral to the incision did not differ significantly between the groups. Aggressive management of early postoperative pain may reduce the likelihood of long-term post-thoracotomy pain.
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              Preoperative assessment enables the early diagnosis and successful treatment of lymphedema.

              The incidence of breast cancer (BC)-related lymphedema (LE) ranges from 7% to 47%. Successful management of LE relies on early diagnosis using sensitive measurement techniques. In the current study, the authors demonstrated the effectiveness of a surveillance program that included preoperative limb volume measurement and interval postoperative follow-up to detect and treat subclinical LE. LE was identified in 43 of 196 women who participated in a prospective BC morbidity trial. Limb volume was measured preoperatively and at 3-month intervals after surgery. If an increase>3% in upper limb (UL) volume developed compared with the preoperative volume, then a diagnosis of LE was made, and a compression garment intervention was prescribed for 4 weeks. Upon reduction of LE, garment wear was continued only during strenuous activity, with symptoms of heaviness, or with visible swelling. Women returned to the 3-month interval surveillance pathway. Statistical analysis was a repeated-measures analysis of variance by time and limb (P
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                May 2016
                20 May 2016
                : 95
                : 20
                : e3705
                Affiliations
                From the Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam (H-SN, A-YO, B-WK, J-HR, J-WH); Department of Anesthesiology and Pain Medicine, Yonsei Barun Orthopedic Clinic, Yongin (D-JL), Gyeonggi; and Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul (A-YO, J-HR), Republic of Korea.
                Author notes
                Correspondence: Ah-Young Oh, Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam-si, Gyeonggi-do 13620, Republic of Korea (e-mail: oay1@ 123456snubh.org)
                Article
                03705
                10.1097/MD.0000000000003705
                4902427
                27196485
                3b9d08c6-959e-4e0c-8682-e36fcc7222d6
                Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

                This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 5 April 2016
                : 14 April 2016
                : 21 April 2016
                Categories
                3300
                Research Article
                Clinical Trial/Experimental Study
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