Investigating the potential of minocycline in reducing brain inflammation in chronic low back pain: a randomized, placebo-controlled mechanistic clinical trial
Mehrbod Mohammadian, Erin J. Morrissey, Paulina C. Knight, Ludovica Brusaferri, Minhae Kim, Nikos Efthimiou, Jennifer Murphy, Zeynab Alshelh, Grace Grmek, Jack H. Schnieders, Courtney A. Chane, Angelica Sandström, Ciprian Catana, Jodi M. Gilman, Joseph J. Locascio, Robert R. Edwards, Yi Zhang, Vitaly Napadow, Marco L. Loggia
Abstract
ABSTRACT: Our group has shown that translocator protein (TSPO) levels, a putative marker of neuroinflammation, are increased in the brain and spinal cord of patients with chronic low back pain (cLBP). Whether neuroinflammation might be a therapeutic target for this condition is unknown. In this phase II double-blind, placebo-controlled, randomized clinical trial, we sought to evaluate whether the tetracycline antibiotic minocycline, which is commonly used as a glial inhibitor in preclinical models, has an effect on brain TSPO levels in adults with cLBP. Participants randomly received 100-mg minocycline or placebo, once a day for 2 weeks. The primary outcome was the change (pretreatment vs posttreatment) in thalamic TSPO levels, measured using [11C]PBR28 positron emission tomography signal (standardized uptake value ratio) and analyzed with a mixed effect model. Secondary outcome measures included the change in Brief Pain Inventory, severity subscore. Among 60 enrolled participants, 48 completed the trial. Of these, 25 received minocycline (age [years], mean ± SD: 44.6 ± 16.9; 9 female), and 23 received placebo (49 ± 17.1; 9 female). The mean thalamic positron emission tomography standard uptake value ratio was very stable across visits in both groups, with no significant group-by-time interaction (P = 0.956). Similarly, both groups demonstrated a comparable decrease over time in Brief Pain Inventory severity scores (P = 0.018) and no significant group-by-time interaction (P = 0.329). Our results suggest that minocycline, at the tested regimen, may neither reduce brain TSPO levels nor have clinically meaningful effects on clinical pain in patients with cLBP.