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

doi:10.1007/s40122-021-00297-2

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

Pain Ther. 2021 Dec;10(2):1375-1400. doi: 10.1007/s40122-021-00297-2. Epub 2021 Aug 10.

Authors

Diane Reckziegel^{1

2}, Pascal Tétreault², Mariam Ghantous², Kenta Wakaizumi^{1

3}, Bogdan Petre², Lejian Huang^{1

2}, Rami Jabakhanji^{1

2

3}, Taha Abdullah², Etienne Vachon-Presseau², Sara Berger², Alexis Baria², James W Griffith^{1

4}, Marwan N Baliki^{1

3}, Thomas J Schnitzer^{1

5

6}, A Vania Apkarian^{7

8

9

10

11}

Affiliations

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.

Keywords: Brain imaging; Chronic pain; Dopamine; Naproxen; Prevention.

Associated data

ClinicalTrials.gov/NCT01951105

Abstract

Associated data

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