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      Relationship Between Pain Reduction and Improvement in Health-Related Quality of Life in Patients with Knee Pain Due to Osteoarthritis Receiving Duloxetine: Exploratory Post Hoc Analysis of a Japanese Phase 3 Randomized Study

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          This post hoc analysis of a Japanese phase 3 randomized study (ClinicalTrials.gov identifier: NCT02248480) investigated relationships between changes in pain severity and changes in health-related quality of life (HRQoL) in duloxetine-treated patients with knee osteoarthritis (OA).

          Patients and Methods

          Patients with knee OA and Brief Pain Inventory (BPI) average pain score ≥4 received duloxetine 60 mg/day or placebo for 14 weeks. Spearman rank correlation coefficients were calculated for change in pain severity, as assessed by the BPI, and change in HRQoL, as assessed by the items of the (i) 36-item Short-Form Health Survey (SF-36; a generic measure of HRQoL) and (ii) Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; an OA-specific measure of HRQoL).


          After 14 weeks of treatment, there was a significantly greater improvement (p<0.001) for duloxetine (n=177) vs placebo (n=176) in BPI average pain severity score and significantly greater improvements (p<0.01) for duloxetine vs placebo for 5 of the 8 SF-36 domains (including the Role-Physical, Bodily Pain, and Physical Functioning domains) and all 24 individual WOMAC items. The correlation between BPI change from baseline and SF-36 item change from baseline was statistically significant (p<0.05) for 2 of the 8 SF-36 items (Bodily Pain, Physical Functioning) in duloxetine-treated patients. The correlation between BPI change from baseline and WOMAC item change from baseline was statistically significant for 22 of the 24 WOMAC items in duloxetine-treated patients.


          This post hoc analysis suggested that the pain reduction observed in duloxetine-treated patients with knee OA was associated with improvements in OA-specific aspects of HRQoL, ie, pain and physical functioning.

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          Most cited references 19

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          Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain

          Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain.
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            Reward and motivation in pain and pain relief.

            Pain is fundamentally unpleasant, a feature that protects the organism by promoting motivation and learning. Relief of aversive states, including pain, is rewarding. The aversiveness of pain, as well as the reward from relief of pain, is encoded by brain reward/motivational mesocorticolimbic circuitry. In this Review, we describe current knowledge of the impact of acute and chronic pain on reward/motivation circuits gained from preclinical models and from human neuroimaging. We highlight emerging clinical evidence suggesting that anatomical and functional changes in these circuits contribute to the transition from acute to chronic pain. We propose that assessing activity in these conserved circuits can offer new outcome measures for preclinical evaluation of analgesic efficacy to improve translation and speed drug discovery. We further suggest that targeting reward/motivation circuits may provide a path for normalizing the consequences of chronic pain to the brain, surpassing symptomatic management to promote recovery from chronic pain.
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              Individual differences in reward responding explain placebo-induced expectations and effects.

              Expectations, positive or negative, are modulating factors influencing behavior. They are also thought to underlie placebo effects, impacting perceptions and biological processes. Using healthy human subjects, we examined the role of the nucleus accumbens (NAC), a region centrally involved in the encoding of reward expectation, in the formation of placebo responses. Employing functional molecular imaging, activation of NAC dopamine (DA) release was observed during placebo administration and related to its anticipated effects, perception-anticipation mismatches, and placebo effect development. In additional functional MRI studies, the expectation of monetary gain increased NAC synaptic activity in a manner proportional to placebo-induced DA release, anticipated effects, perception-anticipation differentials, and actual placebo effects. Individual variations in NAC response to reward expectation accounted for 28% of the variance in the formation of placebo analgesia.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                20 January 2020
                : 13
                : 181-191
                [1 ]Medicines Development Unit Japan, Eli Lilly Japan K.K ., Tokyo 107-0052, Japan
                [2 ]Medicines Development Unit Japan, Eli Lilly Japan K.K ., Kobe 651-0086, Japan
                [3 ]Medical Affairs Department, Shionogi & Co., Ltd., Shibata , Osaka 530-0012, Japan
                [4 ]Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo , Tokyo, Japan
                Author notes
                Correspondence: Hiroyuki Enomoto Medicines Development Unit Japan, Eli Lilly Japan K.K ., 4-15-1-13F, Akasaka, Minato-Ku, Tokyo107-0052, JapanTel +81 3 5574 9143Fax +81 3 5574 9979 Email enomoto_hiroyuki@lilly.com
                © 2020 Enomoto et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Tables: 4, References: 28, Pages: 11
                Funded by: Shionogi & Co., Ltd., Eli Lilly Japan K.K., and Eli Lilly and Company
                Funded by: Eli Lilly Japan K.K. ProScribe’s services
                This study was sponsored by Shionogi & Co., Ltd., Eli Lilly Japan K.K., and Eli Lilly and Company. Medical writing assistance was provided by Justine Southby, PhD, CMPP, and Tania Dickson, PhD, CMPP, of ProScribe – Envision Pharma Group, and was funded by Eli Lilly Japan K.K. ProScribe’s services complied with international guidelines for Good Publication Practice (GPP3).
                Original Research


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