Naohiro Itoh1, Toshinaga Tsuji2, Mitsuhiro Ishida3, Toshimitsu Ochiai4, Shinichi Konno5, Yuji Uchio6. 1. Medical Affairs Department, Shionogi & Co., Ltd., Osaka, Japan. 2. Medical Affairs Department, Shionogi & Co., Ltd., Osaka, Japan. Electronic address: toshinaga.tsuji@shionogi.co.jp. 3. Project Management Development Department, Shionogi & Co., Ltd., Osaka, Japan. 4. Biostatistics Center, Shionogi & Co., Ltd., Osaka, Japan. 5. Department of Orthopaedic Surgery, Fukushima Medical University, Fukushima, Japan. 6. Department of Orthopaedic Surgery, Shimane University School of Medicine, Shimane, Japan.
Abstract
BACKGROUND: Central sensitization, including dysfunction of descending inhibitory pain pathways, may contribute to multisite pain in patients with chronic musculoskeletal conditions. Duloxetine is a centrally acting analgesic that effectively reduces pain in patients with knee osteoarthritis. Here we assessed the efficacy of duloxetine (60 mg/day) in Japanese patients (N = 353) with pain due to knee osteoarthritis based on the number of painful body sites, determined using the Michigan Body Map. METHODS: Post hoc analysis of a phase 3, randomized, placebo-controlled trial (ClinicalTrials.gov; NCT02248480). RESULTS: At Week 14, the change from baseline in Brief Pain Inventory-Severity average pain score ("pain reduction") was significantly greater with duloxetine compared with placebo in patients with 3, 4, or ≥5 painful sites, but not in patients with 1 or 2 painful sites. In patients with ≥3 painful sites (57% of patients), pain reduction was significantly greater with duloxetine (n = 100) compared with placebo (n = 101) throughout the study (least squares mean change from baseline to Week 14: -2.68 vs -1.68). Greater pain reduction with duloxetine (n = 77) than placebo (n = 75) also occurred in patients with ≤2 painful sites, although the between-group difference was significant only at Week 4. CONCLUSIONS: These results are consistent with duloxetine enhancing the activity of descending inhibitory pain pathways that are dysfunctional in patients with central sensitization and multisite pain. In addition, these results suggest that duloxetine may be an effective choice of analgesic for patients with knee osteoarthritis and multisite pain.
RCT Entities:
BACKGROUND: Central sensitization, including dysfunction of descending inhibitory pain pathways, may contribute to multisite pain in patients with chronic musculoskeletal conditions. Duloxetine is a centrally acting analgesic that effectively reduces pain in patients with knee osteoarthritis. Here we assessed the efficacy of duloxetine (60 mg/day) in Japanese patients (N = 353) with pain due to knee osteoarthritis based on the number of painful body sites, determined using the Michigan Body Map. METHODS: Post hoc analysis of a phase 3, randomized, placebo-controlled trial (ClinicalTrials.gov; NCT02248480). RESULTS: At Week 14, the change from baseline in Brief Pain Inventory-Severity average pain score ("pain reduction") was significantly greater with duloxetine compared with placebo in patients with 3, 4, or ≥5 painful sites, but not in patients with 1 or 2 painful sites. In patients with ≥3 painful sites (57% of patients), pain reduction was significantly greater with duloxetine (n = 100) compared with placebo (n = 101) throughout the study (least squares mean change from baseline to Week 14: -2.68 vs -1.68). Greater pain reduction with duloxetine (n = 77) than placebo (n = 75) also occurred in patients with ≤2 painful sites, although the between-group difference was significant only at Week 4. CONCLUSIONS: These results are consistent with duloxetine enhancing the activity of descending inhibitory pain pathways that are dysfunctional in patients with central sensitization and multisite pain. In addition, these results suggest that duloxetine may be an effective choice of analgesic for patients with knee osteoarthritis and multisite pain.