ArticlePain and therapy2021
Sex-Specific Pharmacotherapy for Back Pain: A Proof-of-Concept Randomized Trial.
Article in Pain and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01951105 (Corticostriatal Plasticity in the Transition to Chronic Pain), which is not on this map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Corticostriatal Plasticity in the Transition to Chronic Pain: Effect of L-dopa
Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Dopamine has no direct causal role in the formation of treatment expectations and placebo analgesia in humans.PLoS biology · 2024Trial
- White matter microstructure of sensorimotor projection fibers in chronic low back pain.Pain reports · 2026Article
- Distinct Grey Matter Alterations in Untreated Mild to Moderate Chronic Low Back Pain: A Longitudinal Magnetic Resonance Imaging Study.European journal of pain (London, England) · 2026Observational
- Article
- Synergistic deficits in parvalbumin interneurons and dopamine signaling drive ACC dysfunction in chronic pain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Loss of effort in chronic low-back pain patients: Motivational anhedonia in chronic pain.PloS one · 2025Article
- Body mass index associated with respiration predicts motion in resting-state functional magnetic resonance imaging scans.Human brain mapping · 2024Article
- Impaired muscarinic modulation of the rat prelimbic cortex in neuropathic pain is sexually dimorphic and associated with cold allodynia.Frontiers in cellular neuroscience · 2023Article
- Reward learning in the development and maintenance of chronic back pain.Cell reports. Medicine · 2022Article
- Corticostriatal circuits in the transition to chronic back pain: The predictive role of reward learning.Cell reports. Medicine · 2022Article
- Assessing Pain Research: A Narrative Review of Emerging Pain Methods, Their Technosocial Implications, and Opportunities for Multidisciplinary Approaches.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Decreased dopaminergic inhibition of pyramidal neurons in anterior cingulate cortex maintains chronic neuropathic pain.Cell reports · 2021Article
- The Necessity of Methodological Advances in Pain Research: Challenges and Opportunities.Frontiers in pain research (Lausanne, Switzerland) · 2021Article
- What Is the Numerical Nature of Pain Relief?Frontiers in pain research (Lausanne, Switzerland) · 2021Article
- Brain Imaging Biomarkers for Chronic Pain.Frontiers in neurology · 2021Review
- Influence of exercise on pain is associated with resting-state functional connections: A cross-sectional functional brain imaging study.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPreventing 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.
methodsA 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.
resultsBoth 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.
conclusionsThese 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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.