Diane Reckziegel1,2, Pascal Tétreault2, Mariam Ghantous2, Kenta Wakaizumi1,3, Bogdan Petre2, Lejian Huang1,2, Rami Jabakhanji1,2,3, Taha Abdullah2, Etienne Vachon-Presseau2, Sara Berger2, Alexis Baria2, James W Griffith1,4, Marwan N Baliki1,3, Thomas J Schnitzer1,5,6, A Vania Apkarian7,8,9,10,11. 1. Center for Chronic Pain and Drug Abuse, Northwestern University Feinberg School of Medicine, Chicago, USA. 2. Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, USA. 3. Shirley Ryan AbilityLab, Chicago, USA. 4. Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, Chicago, USA. 5. Department of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, USA. 6. Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, USA. 7. Center for Chronic Pain and Drug Abuse, Northwestern University Feinberg School of Medicine, Chicago, USA. a-apkarian@northwestern.edu. 8. Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, USA. a-apkarian@northwestern.edu. 9. Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, USA. a-apkarian@northwestern.edu. 10. Department of Anesthesia, Northwestern University Feinberg School of Medicine, Chicago, USA. a-apkarian@northwestern.edu. 11. Physiology, Anesthesia, PM&R, Center for Translational Pain Research, Center of Excellence for Chronic Pain and Drug Abuse Research, Northwestern University, Feinberg School of Medicine, Tarry Bldg. 7-705, Chicago, IL, 60611, USA. a-apkarian@northwestern.edu.
Abstract
BACKGROUND: Preventing transition to chronic back pain (CBP) is a long-sought strategy that could rescue patients from prolonged suffering. Recent rodent and human brain imaging studies suggest involvement of sexually dimorphic, dopaminergic-motivational, mesolimbic circuits in the transition to chronic pain (tCBP), and hint that the combination of carbidopa/levodopa and naproxen (LDP + NPX) may block tCBP. Here we evaluated, in people with recent-onset back pain, whether a 3-month treatment with LDP + NPX is safe, blocks tCBP, and whether its efficacy is sex-dependent. METHODS: A total of 72 participants were enrolled and stratified by risk for tCBP using brain-imaging biomarkers. Low-risk participants entered a no-treatment arm. Others were randomized to placebo + naproxen or LDP + NPX for 3 months. RESULTS: Both treatments resulted in more than 50% pain relief for approximately 75% of participants. A strong sex by treatment interaction was observed for daily pain intensity (phone NRS, P = 0.007), replicated on 4-week average pain (Pain/4w, P = 0.00001), and in intent-to-treat analysis (Pain/4w, P = 0.000004). Nucleus accumbens functional connectivity with medial prefrontal cortex, a predefined objective biomarker, showed sex dependence at baseline (P = 0.03) and sex-by-treatment interaction effect 3 months after treatment cessation (P = 0.031). Treatment modified the psychological profile of participants, and disrupted brain modeling-based predicted back pain intensity trajectories. Forty participants were queried 3.3 years from trial start; back pain ratings were similar between end of treatment and at 3.3 years (P = 0.62), indicating persistence of relief for this duration. CONCLUSIONS: These results provide the first evidence for preventing transition to chronic back pain using sex-specific pharmacotherapy. These provocative observations require confirmation in a larger study. ClinicalTrials.gov identifier: NCT01951105.
RCT Entities:
BACKGROUND: Preventing transition to chronic back pain (CBP) is a long-sought strategy that could rescue patients from prolonged suffering. Recent rodent and human brain imaging studies suggest involvement of sexually dimorphic, dopaminergic-motivational, mesolimbic circuits in the transition to chronic pain (tCBP), and hint that the combination of carbidopa/levodopa and naproxen (LDP + NPX) may block tCBP. Here we evaluated, in people with recent-onset back pain, whether a 3-month treatment with LDP + NPX is safe, blocks tCBP, and whether its efficacy is sex-dependent. METHODS: A total of 72 participants were enrolled and stratified by risk for tCBP using brain-imaging biomarkers. Low-risk participants entered a no-treatment arm. Others were randomized to placebo + naproxen or LDP + NPX for 3 months. RESULTS: Both treatments resulted in more than 50% pain relief for approximately 75% of participants. A strong sex by treatment interaction was observed for daily pain intensity (phone NRS, P = 0.007), replicated on 4-week average pain (Pain/4w, P = 0.00001), and in intent-to-treat analysis (Pain/4w, P = 0.000004). Nucleus accumbens functional connectivity with medial prefrontal cortex, a predefined objective biomarker, showed sex dependence at baseline (P = 0.03) and sex-by-treatment interaction effect 3 months after treatment cessation (P = 0.031). Treatment modified the psychological profile of participants, and disrupted brain modeling-based predicted back pain intensity trajectories. Forty participants were queried 3.3 years from trial start; back pain ratings were similar between end of treatment and at 3.3 years (P = 0.62), indicating persistence of relief for this duration. CONCLUSIONS: These results provide the first evidence for preventing transition to chronic back pain using sex-specific pharmacotherapy. These provocative observations require confirmation in a larger study. ClinicalTrials.gov identifier: NCT01951105.
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