TY - JOUR
T1 - The Effect of Duloxetine on Mechanistic Pain Profiles, Cognitive Factors, and Clinical Pain in Patients with Painful Knee Osteoarthritis – A Randomized, Double-Blind, Placebo-Controlled, Crossover Study
AU - Petersen, Kristian Kjær-Staal
AU - Drewes, Asbjørn Mohr
AU - Olesen, Anne Estrup
AU - Ammitzbøll, Nadia
AU - Bertoli, Davide
AU - Brock, Christina
AU - Arendt-Nielsen, Lars
N1 - Center for Neuroplasticity and Pain (CNAP) is supported by the Danish National Research Foundation (DNRF121). The Aalborg University Talent Management Programme (j.no. 771126), The Danish Rheumatism Association (grant number: A6579), The Shionogi Science Program, and the TaNeDS Daiichi Sankyo Science Center Europe grant funded the study.
© 2022 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.
PY - 2022/9
Y1 - 2022/9
N2 - Background: Duloxetine is indicated in the management of pain in osteoarthritis. Evidence suggests that duloxetine modulates central pain mechanisms and cognitive factors, and these factors are assumed contributing to the analgesic effect. This proof-of-mechanism, randomized, placebo-controlled, crossover, double-blinded trial evaluated the effect of duloxetine on quantitative sensory testing (QST), cognitive factors and clinical pain in patients with osteoarthritis and to predict the analgesic effect. Methods: Twenty-five patients completed this cross-over study with either 18-week duloxetine (maximum 60 mg/daily) followed by placebo or vice-versa. Pressure pain thresholds, temporal summation of pain and conditioned pain modulation were assessed using cuff algometry. The Hospital Anxiety and Depression Scale and the Pain Catastrophizing Scale evaluated cognitive factors. Clinical pain was assessed using Brief Pain Inventory and Western Ontario and McMaster Universities Osteoarthritis Index. Linear regression models were used to predict the analgesic effect of duloxetine. Results: Depending on the clinical pain outcome, 40%–68% of patients were classified as responders to duloxetine. Linear regression models predicted the analgesic effect (predictive value of 45%–75% depending on clinical pain outcome parameter) using a combination of pretreatment QST parameters, cognitive factors and clinical pain. No significant changes were found for QST, cognitive factors or clinical pain on a group level when comparing duloxetine to placebo. Conclusion: A combination of pretreatment QST, cognitive factors and clinical pain was able to predict the analgesic response of duloxetine. However, in this relatively small study, duloxetine did not selectively modulate QST, cognitive factors or clinical pain intensity when compared with placebo. Significance: Duloxetine is proposed as a treatment for chronic pain. Pre-clinical trials suggest that duloxetine provides analgesia through modulation of descending pain inhibitory pathways or through improvements in cognitive factors. The current study demonstrates that pretreatment mechanistic pain profiling, cognitive factors and clinical pain can predict the analgesic effect of duloxetine and that only a subset of patients might benefit from duloxetine treatment.
AB - Background: Duloxetine is indicated in the management of pain in osteoarthritis. Evidence suggests that duloxetine modulates central pain mechanisms and cognitive factors, and these factors are assumed contributing to the analgesic effect. This proof-of-mechanism, randomized, placebo-controlled, crossover, double-blinded trial evaluated the effect of duloxetine on quantitative sensory testing (QST), cognitive factors and clinical pain in patients with osteoarthritis and to predict the analgesic effect. Methods: Twenty-five patients completed this cross-over study with either 18-week duloxetine (maximum 60 mg/daily) followed by placebo or vice-versa. Pressure pain thresholds, temporal summation of pain and conditioned pain modulation were assessed using cuff algometry. The Hospital Anxiety and Depression Scale and the Pain Catastrophizing Scale evaluated cognitive factors. Clinical pain was assessed using Brief Pain Inventory and Western Ontario and McMaster Universities Osteoarthritis Index. Linear regression models were used to predict the analgesic effect of duloxetine. Results: Depending on the clinical pain outcome, 40%–68% of patients were classified as responders to duloxetine. Linear regression models predicted the analgesic effect (predictive value of 45%–75% depending on clinical pain outcome parameter) using a combination of pretreatment QST parameters, cognitive factors and clinical pain. No significant changes were found for QST, cognitive factors or clinical pain on a group level when comparing duloxetine to placebo. Conclusion: A combination of pretreatment QST, cognitive factors and clinical pain was able to predict the analgesic response of duloxetine. However, in this relatively small study, duloxetine did not selectively modulate QST, cognitive factors or clinical pain intensity when compared with placebo. Significance: Duloxetine is proposed as a treatment for chronic pain. Pre-clinical trials suggest that duloxetine provides analgesia through modulation of descending pain inhibitory pathways or through improvements in cognitive factors. The current study demonstrates that pretreatment mechanistic pain profiling, cognitive factors and clinical pain can predict the analgesic effect of duloxetine and that only a subset of patients might benefit from duloxetine treatment.
UR - http://www.scopus.com/inward/record.url?scp=85131741621&partnerID=8YFLogxK
U2 - 10.1002/ejp.1988
DO - 10.1002/ejp.1988
M3 - Journal article
C2 - 35638317
SN - 1090-3801
VL - 26
SP - 1650
EP - 1664
JO - European Journal of Pain
JF - European Journal of Pain
IS - 8
ER -