Evaluating the Role of Neuroinflammation in Low Back Pain (IGNITE)

In this research, the study team will use brain imaging to evaluate the presence of neuroinflammation in the brains and spinal cords of patients with low back pain. The efficacy of minocycline use for low back pain treatment will also be evaluated by observing whether short-term minocycline administration will reduce neuroinflammation and low back pain symptoms.

The goal of this research study is to evaluate whether the central nervous systems of those with low back pain are different from those of healthy, pain-free individuals. Specifically, the researchers will test whether "glial cells" (the immune cells of the brain and spinal cord) are more active in patients with low back pain than in healthy volunteers. The investigators' previous study showed that patients with chronic low back pain demonstrated elevations in brain levels of the 18kDa translocator protein (TSPO), a marker of glial activation. To test this hypothesis, the study team will image the brains and spinal cords of patients suffering from low back pain using integrated magnetic resonance- positron emission tomography (MR-PET), and a radiotracer called [11C]PBR28, which tracks levels of glial activation. The efficacy of minocycline as a treatment for chronic low back pain will also be evaluated. A recent study demonstrated a statistically significant reduction in pain in those with lumbar radiculopathy after treatment with minocycline, leading the investigators of this study to believe that minocycline may have potential efficacy in treating other back pain populations. The study team will observe whether a short course of minocycline hydrochloride may reduce glial activation along with self-reported low back pain symptoms. To this end, patients will be evaluated clinically and/or re-scanned after completing a 2-week trial of minocycline or placebo (a sugar pill). This study will be enrolling individuals who have been suffering from sub-acute (short-term) and chronic low back pain.

Low Back Pain, Back Pain With Radiation, Back Pain Without Radiation, Back Pain Lower Back Chronic, Back Ache, Pain, Chronic

Microglia, Minocycline, Magnetic Resonance Imaging, Positron Emission Tomography, Pain, Astrocytes, Glia, Human, Back Pain

Evaluation with Magnetic Resonance-Positron Emission Tomography Imaging and/or behavioral pain assessment before and after a 2-week trial of Minocycline Hydrochloride, 100mg capsule

Evaluation with Magnetic Resonance-Positron Emission Tomography Imaging and/or behavioral pain assessment before and after 2 weeks of treatment with a placebo capsule.

Up to 15 millicuries of [11C]PBR28 will be administered to each subject at each imaging visit, for a maximum of 2 imaging visits.

The investigators will test for the presence of a significant treatment*time interaction in the brain [11C]PBR28 signal.

The investigators will test for the presence of a significant treatment*time interaction in the spinal [11C]PBR28 signal.

The investigators will test for the presence of a significant treatment*time interaction in pain outcomes on a self reported numerical (0-100) pain rating scale.

Inclusion Criteria: the ability to give written informed consent fluency in English on a stable pain treatment Chronic or sub-acute low back pain Exclusion Criteria: no interventional pain procedures during drug trial contraindications to MRI and PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia) pregnancy or breast feeding any use of recreational drugs in the past 6 months allergy to minocycline or other tetracyclines, or taking medications known to interact with minocycline any other contraindications to minocycline administration

Loggia ML, Chonde DB, Akeju O, Arabasz G, Catana C, Edwards RR, Hill E, Hsu S, Izquierdo-Garcia D, Ji RR, Riley M, Wasan AD, Zurcher NR, Albrecht DS, Vangel MG, Rosen BR, Napadow V, Hooker JM. Evidence for brain glial activation in chronic pain patients. Brain. 2015 Mar;138(Pt 3):604-15. doi: 10.1093/brain/awu377. Epub 2015 Jan 12.

Vanelderen P, Van Zundert J, Kozicz T, Puylaert M, De Vooght P, Mestrum R, Heylen R, Roubos E, Vissers K. Effect of minocycline on lumbar radicular neuropathic pain: a randomized, placebo-controlled, double-blind clinical trial with amitriptyline as a comparator. Anesthesiology. 2015 Feb;122(2):399-406. doi: 10.1097/ALN.0000000000000508.