This study is designed to examine brain properties for placebo response in chronic back pain patients. The investigators have preliminary data indicating that, in blinded clinical trial studies with neutral instructions regarding treatment, chronic back pain (CBP) patients can be subdivided into placebo responders and non-responders, and these differences are PREDICTABLE a priori, by brain activity. The results imply that CBP placebo may have clinical utility and that its properties can be studied by human brain imaging techniques. In Phase I of the study, the investigators seek to identify brain imaging parameters that predict the propensity for the placebo response in an independent CBP cohort. In Phase II, the investigators will evaluate the interaction between placebo response and medication treatment in individuals stratified as placebo responders versus non-responders. This research is designed to critically assess the neurobiology of placebo analgesia for chronic pain in a partially-blind clinical trial.

Visit 1 (week -3): Screening visit (90 min):

Participants will be evaluated with inclusion/exclusion criteria and complete the informed consent documents. A medical/pain history will be taken and physical exam will be completed by a physician and participants will be asked to rate their current back pain intensity. Participants will complete a set of 10 questionnaires that will ask about health and medical history, past and current pain levels, personality, and emotions. Participants will be allowed to take breaks and walk around during this time so that participants don't get tired while filling out questionnaires. Finally, participants will have blood drawn for screening purposes including to see if kidneys and liver are functioning as they should (the investigators will take 40 mL or about 8 teaspoons). Participants will be asked to return in 2 weeks for baseline magnetic resonance imaging (MRI) scans. Participants will be asked to discontinue current pain medications 14 days prior to Visit 2 and take only the rescue medication ("rescue" medication that is also known as acetaminophen/Tylenol ®), given for pain during this time (see below) - this is so that the investigators can assess baseline amount of pain. Participants will be informed that they may be randomized in the placebo group and/or the no-treatment group (Visit 3) once one qualifies to continue in the study. Participants must, therefore,a be willing and able to stop taking the medication for pain for up to a maximum of 12 weeks during this study. Participants will be given acetaminophen (500 mg, up to 4 times per day) to take for pain relief (as rescue medication), a dose that can be continued throughout the study. Participants are free to stop participation at any point in the study. Participants randomized into the treatment arm may receive the anti-inflammatory drug naproxen, since it is known to increase the risk of stomach and intestinal side effects, a combined naproxen/esomeprazole drug regimen will be given to participants to provide some protection for these types of side effects.

Visit 2 (week -1): Baseline Scan (90 min):

Participants will rate their pain intensity, complete questionnaires, and undergo brain scanning (anatomical and functional scans). Participants will receive medication, which can be used if the pain becomes too much to handle (500 mg four times per day maximum). The researcher will ask participants about how often participants used the "rescue" medication and any changes in health they may have experienced since the last visit.

Visit 3 (week 0): Start of Treatment Period and Randomization (30-45 min):

Participants will rate their pain intensity and complete questionnaires. Participants will be randomized into either a drug (placebo or naproxen and esomeprazole) treatment group or no treatment group; if participants are assigned to a treatment group (active or placebo), neither participants nor the clinical coordinator/assistant will know which group participants are allocated in. Enough medication will be given to participants to last until the next visit. The placebo group will receive two placebo capsules twice daily and the active drug group will receive one naproxen capsule (500mg) and one esomeprazole capsule (20mg) twice daily (morning and night) for the treatment period. The medication (Naproxen or Placebo) needs to be taken with at least one full glass (8 oz) of water and the other medication (Esomeprazole or Placebo) should be taken one hour before a meal. The researcher will provide the study medication; if participants were randomized into the no treatment group, participants will only receive rescue medication. The researcher will ask participants about how often participants used the "rescue" medication and any side effects participants experienced since Visit 2 took place. Additional "rescue" medication will be given.

Visit 4 (week 3): Continuing Assessment (30-45 min). The procedures described for Visit 3 will be repeated during this visit. The researcher will ask participants about how often they used the "rescue" medication and any side effects experienced since Visit 3 took place. As well, the researcher will ask how often participants took the study medication (if in a treatment group) and document the total pills ingested.

Visit 5 (week 6): End of Treatment/Start of Washout and Final Scan (60-90 min):

The procedures described for Visit 2 will be repeated during this visit. The researcher will ask participants about how often and reliably participants took the medication (if in a treatment group), as well as how often they used the "rescue" medication and any side effects experienced since Visit 4 took place. Participants will only receive the "rescue" medication for the upcoming 3 weeks.

Visit 6 (week 9): Final Visit/End of Washout (30-45 min):

Participants will return to complete questionnaires, but no brain scans will be done. The researcher will ask participants about how often they used the "rescue" medication and any side effects experienced since Visit 5 took place. If participants are in one of the treatment groups, participants will be asked to return all of the study medication and rescue medication at this time, and all treatment will be stopped at this visit.

Inclusion Criteria:

• History of low back pain for a minimum of 6 months with or without signs and symptoms of radiculopathy
• Male or female, between the ages of 18 and 75 years, with no racial or ethnic restrictions
• Must have a Visual Analog Scale (VAS) pain score of 5 mm (of 10 mm maximum) at the screening visit (for which 0mm = no pain, and 10 mm = worst pain imaginable);
• Must be able to read and speak English and be willing to read and understand instructions as well as questionnaires;
• Must be in generally stable health;
• Must sign an informed consent document after a complete explanation of the study documenting that they understand the purpose of the study, procedures to be undertaken, possible benefits, potential risks, and are willing to participate
• Must have, on average, 5/10 units (VAS scale) of pain over the course of a two-week period prior to visit 1; rounding up from 4.5/10 is permissible.
• Must be willing to complete daily smart phone/computer app ratings.

Exclusion Criteria:

• Low back pain associated with any systemic signs or symptoms, e.g., fever, chills;
• Evidence of rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, fibromyalgia, history of tumor in the back;
• Other comorbid chronic pain or neurological conditions;
• Involvement in litigation regarding their back pain or having a disability claim or receiving workman's compensation or seeking either as a result of their low back pain;
• Diagnosis of current depression or psychiatric disorder requiring treatment, or such a diagnosis in the previous 6 months;
• Beck Depression Inventory (BDI) Ia score greater or equal to 19 for two consecutive completions; if the first score meets this criteria, the participant must be re-tested before his/her next visit, but if the second score does not meet this criteria, the participant will be included and followed closely throughout the study
• Use of therapeutic doses of antidepressant medications (i.e., tricyclic depressants, SSRIs, SNRIs; low doses used for sleep may be allowed);
• Significant other medical disease such as unstable diabetes mellitus, congestive heart failure, coronary or peripheral vascular disease, chronic obstructive lung disease, or malignancy;
• History of gastrointestinal ulcer during the past year;
• History of myocardial infarction in the past year;
• Uncontrolled hypertension;
• Renal insufficiency;
• Allergic to, or non-tolerant of, NSAIDs;
• History of aspirin-sensitive asthma;
• Current use of recreational drugs or history of alcohol or drug abuse;
• Any change in medication for back pain in the last 30 days only applicable for visit 1
• High dose opioid prophylaxis, as defined as > 50mg morphine equivalent/day;
• Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk;
• In the judgment of the investigator, unable or unwilling to follow protocol and instructions;
• Evidence of poor treatment compliance, in the judgment of the investigator;
• Intra-axial implants (e.g. spinal cord stimulators or pumps);
• All exclusion criteria for MR safety: any metallic implants, brain or skull abnormalities, tattoos on large body parts, and claustrophobia;
• Pregnancy, or inability to use an effective form of contraception in women of child-bearing age;
• Diabetes (Type I or Type II);
• Lactose intolerance or sensitivity to lactose

12 weeks

collected at each one of the 6 visits

This study has several limitations including:

1. The biosignature was poor predictability of individual participants' magnitude of pain relief, e
2. The univariate analyses suggest that some features of the model could be further optimized