TY - JOUR
T1 - Sex-Specific Pharmacotherapy for Back Pain
T2 - A Proof-of-Concept Randomized Trial
AU - Reckziegel, Diane
AU - Tétreault, Pascal
AU - Ghantous, Mariam
AU - Wakaizumi, Kenta
AU - Petre, Bogdan
AU - Huang, Lejian
AU - Jabakhanji, Rami
AU - Abdullah, Taha
AU - Vachon-Presseau, Etienne
AU - Berger, Sara
AU - Baria, Alexis
AU - Griffith, James W.
AU - Baliki, Marwan N.
AU - Schnitzer, Thomas J.
AU - Apkarian, A. Vania
N1 - Funding Information:
The study and journal’s Rapid Service Fee was funded by the National Institute of Dental and Craniofacial Research (Blue Print Grant number R01DE022746) and in part by National Institute on Drug Abuse (P50 DA044121).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Brain imaging
KW - Chronic pain
KW - Dopamine
KW - Naproxen
KW - Prevention
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U2 - 10.1007/s40122-021-00297-2
DO - 10.1007/s40122-021-00297-2
M3 - Article
AN - SCOPUS:85112161572
SN - 2193-8237
VL - 10
SP - 1375
EP - 1400
JO - Pain and Therapy
JF - Pain and Therapy
IS - 2
ER -