Neuropathic pain affects the quality of life of many Americans. Non-pharmacological strategies such as bioactive compounds in foods are being explored as therapeutics but can also serve as tools to better understand pain mechanisms. The previous study reported that ginger root extract supplementation palliated pain-spectrum behaviors in animals with neuropathic pain via the microbiota-gut-brain axis. The proposed study is primarily designed to use ginger supplementation for a better understanding of the role of microbiota-gut-brain interactions in sciatica states in a randomized, double-blinded, and placebo-controlled trial. Eighty participants with sciatica will be randomized to receive placebo (2000 mg starch daily) or ginger (2000 mg daily) for 8 weeks. This study will evaluate the effects of ginger supplementation on gut function measured as gut microbiota composition using 16S rRNA sequencing analysis, intestinal permeability based on plasma lipopolysaccharide binding protein and fecal zonulin using ELISA, and fecal metabolites using LC-MS/MS analysis (SA 1); on neuroinflammation in whole blood mRNA using nCounter® Neuroinflammation Panels analysis (SA 2); and on pain-associated outcomes and brain neuroplasticity by assessing functional (resting state-fMRI) and structural (Diffusion Tensor Imaging) connectivity (SA 3).

Inclusion criteria:

• 18-85 years old men and women with BMI < 25 or ≥ 30 kg/m2
• low back or gluteal pain radiating into leg(s) past the knee (sciatica) with pain duration of at least 3 months (chronic sciatica)
• pain scale > 3 out of 10 (0=no pain,10=worst pain imaginable) during the past 24 hours
• willingness to accept randomization.
• woman of childbearing potential agrees to use an effective form of contraception during the study

Exclusion criteria:

Sciatica aspects:

• known or suspected serious spinal pathology (e.g., cauda equina syndrome or spinal fracture)
• scheduled, or being considered, for spinal surgery or interventional procedures for sciatica during study period
• focal neurological deficits with progressive or disabling symptoms
• low back pain without sciatica

GI aspects:

• unstable GI disorder
• history of chronic or systemic autoimmune diseases with GI involvement
• recent (<1 month) appearance of diarrhea or hematochezia before study begins
• recent (<1 month) exposure to antibiotics before study start

Other exclusion considerations:

• pregnant or breast-feeding women
• women of child-bearing potential will have a urine pregnancy test done prior to the baseline MRI and administration of any study drug. The clinical research coordinator will run the pregnancy test and inform the patient of the results. If the test is positive, they will be withdrawn from study participation.
• cognitive impairment, history of psychiatric conditions indicating mental health instability or incapacity
• likeliness of moving during the trial, lack of transportation, or unavailability at sample collection times.
• presence of a bleeding diathesis
• taking anticoagulant medications (e.g Heparin, Warfarin)
• taking dual antiplatelet medications (e.g. aspirin + Plavix)
• participants with clinically significant laboratory abnormalities of liver function (AST and ALT) and kidney function (BUN and serum creatinine) abnormalities. Definition of clinically significant for liver function is AST/ALT ≥ 3.0x ULN and for kidney function is serum creatinine > 2.0 mg/dl and BUN > 1.5x ULN.

There is not a plan to make IPD available due to HIPAA regulation.