Inclusion Criteria for Light Phenotyping (all participants):  Definition of cLBP described in the NIH Task Force Report on Research Standards for Chronic Low Back Pain (for example (i.e.), low back pain present at least six months, and present more than half of those days. Individuals must have the eligible protocol pain interference score on PROMIS Pain Interference. Individuals must be willing to be randomized to receive any of the four proposed treatments.  Exclusion Criteria for Light Phenotyping (all participants):  History of discitis osteomyelitis (spine infection) or spine tumor History of ankylosing spondylitis, rheumatoid arthritis, polymyalgia rheumatica, or psoriatic arthritis, lupus History of cauda equina syndrome or spinal radiculopathy with functional motor deficit (strength <4/5 on manual motor testing) Diagnosis of any vertebral fracture in the last 6 months Osteoporosis requiring treatment other than vitamin D and calcium supplements Cancer (History of any bone-related cancer or cancer that metastasized to the bone, Currently in treatment for any cancer or plan to start cancer treatment in the next 12 months, History of any cancer treatment in the last 24 months) Life expectancy less than 2 years Unable to speak and write English Visual or hearing difficulties that would preclude participation Presence of any history that would preclude scanning in magnetic resonance imaging (MRI) Uncontrolled drug/alcohol addiction Individuals receiving disability or compensation within the past year, or involved in litigation Pregnancy or breastfeeding History of allergy to duloxetine Individuals on high doses of opioids (over 100 oral morphine equivalents (OME) per day)  Contraindications to receiving duloxetine:  certain medications (per protocol) renal dysfunction (creatinine clearance <30 milliliters per minute (mL/min) or End-Stage Renal Failure) Hepatic dysfunction: Hepatic impairment defined as having a Child-Pugh score of A-C Scheduled back surgery, back surgery within the last year, or more than one back surgery in the past. Expecting to receive an injection of surgical procedure within the next year for their cLBP Current/planned (in the next 2 years) enrollment in another study of a device or investigational drug that would interfere with this study, this may include participation in a blinded trial. Any other diseases or conditions that would make a patient unsuitable for study participation as determined by the site principal investigators. This would include but not be limited to severe psychiatric disorders, active suicidal ideations or history of suicide attempts, and an uncontrolled drug and/or alcohol addiction  Inclusion Criteria for Deep Phenotyping (subset 160 participants):  Right hand dominant (such as the hand used when writing or throwing/catching a ball) Normal visual acuity or correctable (with corrective lenses- glasses or contacts) to at least 20/40 for reading instructions in the MRI and visual sensitivity testing No contraindications to MRI (i.e., metal implants) Willingness to refrain from taking any "as needed" medications, including pain medications such as Nonsteroidal anti-inflammatory drugs (i.e., Motrin, Advil, Aleve), acetaminophen, and opioids, for 8 hours before undergoing neuroimaging and 10.1 Quantitative Sensory Testing (QST) Willingness to refrain from alcohol and nicotine on the day of QST and neuroimaging (alcohol and nicotine consumption is allowed after testing is completed) Willingness to refrain from any unusual physical activity or exercise that would cause muscle and/or joint soreness for 48 hours prior to testing (routine exercise or activity that does not lead to soreness is acceptable) Able to lie still on back for 2 hours during MRI  Exclusion Criteria for Deep Phenotyping (subset 160 participants):  Severe claustrophobia precluding MRI and evoked pain testing during scanning Diagnosed peripheral neuropathy Current, recent (within the last 6 months), or habitual use of artificial nails or nail enhancements. (Artificial nails can influence pressure pain sensitivity at the thumbnail) Body Mass Index greater than 45 or unable to comfortably fit in the bore of the MRI magnet