Sex-Specific Pharmacotherapy for Back Pain: A Proof-of-Concept Randomized Trial

Diane Reckziegel, Pascal Tétreault, Mariam Ghantous, Kenta Wakaizumi, Bogdan Petre, Lejian Huang, Rami Jabakhanji, Taha Abdullah, Etienne Vachon-Presseau, Sara Berger, Alexis Baria, James W. Griffith, Marwan N. Baliki, Thomas J. Schnitzer, A. Vania Apkarian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1375-1400
Number of pages26
JournalPain and Therapy
Volume10
Issue number2
DOIs
StatePublished - Dec 2021

Keywords

  • Brain imaging
  • Chronic pain
  • Dopamine
  • Naproxen
  • Prevention

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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