What are the medications for chronic Musculoskeletal (MSK) pain?

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Last updated: March 27, 2025View editorial policy

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From the Guidelines

For chronic musculoskeletal pain, I recommend starting with acetaminophen (Tylenol) at 650-1000mg every 6 hours (maximum 3000mg daily) or non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil, Motrin) 400-600mg every 6 hours with food, or naproxen (Aleve) 220-500mg twice daily with food, as these are recommended as first-line agents for the treatment of musculoskeletal pain 1.

Medication Options

  • Acetaminophen: 650-1000mg every 6 hours (maximum 3000mg daily)
  • NSAIDs:
    • Ibuprofen (Advil, Motrin): 400-600mg every 6 hours with food
    • Naproxen (Aleve): 220-500mg twice daily with food
  • Muscle relaxants: cyclobenzaprine 5-10mg at bedtime for short-term use (1-3 weeks)
  • Topical treatments:
    • Diclofenac gel 1% applied to painful areas 4 times daily
    • Lidocaine patches (5%) placed on the painful area for 12 hours daily
  • For persistent pain:
    • Duloxetine 30-60mg daily
    • Gabapentin starting at 300mg daily and gradually increasing to 300-600mg three times daily

Considerations

  • NSAIDs can cause stomach irritation and kidney problems with long-term use 1
  • Acetaminophen has fewer side effects but can damage the liver at high doses 1
  • Always combine medication with physical therapy, gentle exercise, and proper body mechanics for best results
  • Consult your healthcare provider before starting any medication regimen, especially if you have other health conditions or take other medications

Additional Information

  • The use of opioids for chronic musculoskeletal pain is not recommended as a first-line treatment due to the risk of addiction and overdose 1
  • Alternative treatments such as physical therapy, exercise, stress management, and cognitive behavioral therapy may also be effective in managing chronic musculoskeletal pain 1

From the FDA Drug Label

Cyclobenzaprine hydrochloride tablets are indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as: different types of arthritis The following NSAID medicines are listed: * Naproxen * Celecoxib * Diclofenac * Diflunisal * Etodolac * Fenoprofen * Flurbiprofen * Ibuprofen * Indomethacin * Ketoprofen * Ketorolac * Mefenamic Acid * Meloxicam * Nabumetone * Oxaprozin * Piroxicam * Sulindac * Tolmetin

Medications for chronic Musculoskeletal (MSK) pain include:

  • NSAIDs: such as naproxen, celecoxib, diclofenac, diflunisal, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, oxaprozin, piroxicam, sulindac, tolmetin
  • Muscle relaxants: such as cyclobenzaprine 2, 3

From the Research

Medications for Chronic Musculoskeletal (MSK) Pain

The following medications are used to manage chronic musculoskeletal pain:

  • Paracetamol (acetaminophen) as the first-line analgesic agent due to its favourable side effect and safety profile 4
  • Non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac and naproxen, with caution in patients at increased cardiovascular and/or cardiorenal risk 4, 5
  • Cyclooxygenase-2 (COX-2)-selective anti-inflammatory drugs, with caution due to potential cardiovascular and/or cardiorenal effects 4
  • Weak opioids, recommended for addition to paracetamol when greater analgesia is desired, due to a preferable GI and cardiovascular profile compared to NSAIDs 4
  • Antidepressants, such as tricyclic antidepressants and serotonin reuptake inhibitors, for management of chronic pain conditions 6
  • Anticonvulsants, for management of chronic pain conditions 6
  • Topical medications, such as lidocaine, diclofenac, and capsaicin, for management of chronic musculoskeletal pain 6
  • Extended-release tramadol, for management of chronic pain conditions 6

Considerations for Medication Use

When selecting medications for chronic musculoskeletal pain, consideration should be given to:

  • The patient's physiological state and presence of disease(s) 5
  • The potential risks and benefits of each medication, including gastrointestinal, cardiovascular, and renal effects 4, 5
  • The use of medications in combination, such as paracetamol and weak opioids, to achieve effective pain management 4
  • The need for frequent re-evaluation of the cause of chronic pain and the impact on the patient's general medical state 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Management of chronic musculoskeletal pain.

The Journal of the American Academy of Orthopaedic Surgeons, 2014

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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