Sex-Specific Pharmacotherapy for Back Pain: A Proof-of-Concept Randomized Trial
| Autor: | Bogdan Petre, James W. Griffith, Etienne Vachon-Presseau, Alexis T. Baria, A. Vania Apkarian, Thomas J. Schnitzer, Taha B. Abdullah, Rami Jabakhanji, Marwan N. Baliki, Sara E. Berger, Pascal Tétreault, Mariam E. Ghantous, Kenta Wakaizumi, Lejian Huang, Diane Reckziegel |
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| Rok vydání: | 2021 |
| Předmět: |
Levodopa
medicine.medical_specialty Pain medicine Dopamine Brain imaging Chronic pain law.invention Pharmacotherapy Naproxen Randomized controlled trial law Internal medicine medicine Back pain Prefrontal cortex Original Research business.industry Prevention medicine.disease Anesthesiology and Pain Medicine Carbidopa Neurology (clinical) medicine.symptom business medicine.drug |
| Zdroj: | Pain and Therapy |
| ISSN: | 2193-8237 |
| Popis: | 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. Supplementary Information The online version contains supplementary material available at 10.1007/s40122-021-00297-2. |
| Databáze: | OpenAIRE |
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