NSAIDs for Pain: When They Work, When They Don't, and What to Watch For

By H. Rand Scott, MD — Medical Director, Newport Pain Management Reviewed and updated August 2026

Nonsteroidal anti-inflammatory drugs — NSAIDs — are among the most widely used pain medications in medicine. They are useful for musculoskeletal injuries, arthritis, headache, menstrual pain, and post-operative pain, among many other conditions. This article covers how they work, which ones are commonly prescribed, how to take them, and the safety considerations that have become more important as we've learned more about long-term NSAID use.

NSAIDs reduce pain, fever, and inflammation. The category includes both prescription and over-the-counter medications. Common examples:

• Ibuprofen (Motrin, Advil) — OTC and prescription.
• Naproxen (Aleve, Naprosyn, Anaprox) — OTC and prescription.
• Diclofenac (Voltaren, Cataflam) — oral prescription; Voltaren 1% gel is now available over the counter for arthritis pain in specific joints.
• Celecoxib (Celebrex) — a COX-2 selective NSAID with typically lower gastrointestinal risk than nonselective NSAIDs.
• Meloxicam (Mobic) — once-daily NSAID commonly used for arthritis.
• Indomethacin (Indocin) — strong NSAID used for specific indications including gout.
• Ketorolac (Toradol) — short-term use only; strong post-operative and acute pain option.
• Ketoprofen, sulindac, piroxicam — older NSAIDs still available, less commonly used first-line.
• Aspirin — technically an NSAID but used differently. Higher doses were once common for arthritis; that use has largely been replaced by better-tolerated NSAIDs.

Acetaminophen (Tylenol) is often mentioned alongside NSAIDs because it treats pain and fever, but it works differently and does not reduce inflammation. It's a useful complement to NSAIDs in many pain plans.

NSAIDs block the production of prostaglandins — hormone-like chemicals released at the site of tissue injury that drive the pain, heat, redness, and swelling of inflammation. Prostaglandins also sensitize pain-sensing nerve endings (nociceptors) so that even small stimuli feel painful. By blocking prostaglandin production, NSAIDs reduce inflammation at its source and lower the sensitivity of pain nerves.

Prostaglandins have other jobs in the body too — protecting the stomach lining, maintaining kidney blood flow, and supporting normal platelet function. Blocking them everywhere is why NSAIDs have their characteristic side effects.

NSAIDs are available as tablets, capsules, liquid, topical gels, and (in a few cases) injection. Take oral NSAIDs with food or milk to reduce stomach irritation. Some formulations have a protective coating for the same purpose.

Your physician will prescribe a specific dose and schedule based on your condition. Common patterns include:

• Ibuprofen: every 6 to 8 hours.
• Naproxen: twice a day.
• Meloxicam and celecoxib: once daily for most patients.
• Voltaren gel: applied to the specific joint several times a day.

Take the lowest dose that controls your pain, for the shortest time appropriate to your condition. This isn't about being brave — it's about minimizing exposure to the side effects that all NSAIDs carry.

Topical diclofenac (Voltaren 1% gel, other formulations) delivers NSAID directly to a specific joint or muscle with much lower blood levels than oral use. That means significantly less risk of the systemic side effects — stomach, kidney, cardiovascular — that come with oral NSAIDs. Topical NSAIDs are a strong choice for focal joint pain (knee, hand, foot) in patients who need to avoid oral NSAIDs. Voltaren gel has been over-the-counter in the US since 2020.

Common side effects include stomach upset, heartburn, indigestion, and diarrhea. Take with food to reduce these.

More important side effects require awareness rather than routine occurrence:

NSAIDs can cause stomach ulcers, particularly with long-term use, higher doses, in older adults, or when combined with steroids, blood thinners, or alcohol. Signs of a bleeding ulcer include dark or bloody stools, coffee-ground vomit, or new severe abdominal pain — call your doctor promptly if any of these occur. Patients at higher risk for GI bleeding are often placed on an acid-suppressing medication (a proton pump inhibitor) while taking chronic NSAIDs, or shifted to celecoxib, which has lower GI risk.

Extensive research since the withdrawal of rofecoxib (Vioxx) in 2004 has shown that virtually all NSAIDs — not just COX-2 selective drugs — carry some increase in cardiovascular risk with long-term use. The risk varies by drug and by dose. Naproxen has the most favorable cardiovascular profile of the common NSAIDs; diclofenac and higher-dose ibuprofen and celecoxib carry more risk. Patients with existing cardiovascular disease, prior heart attack, or heart failure should discuss NSAID choice carefully with their physician.

NSAIDs reduce blood flow to the kidneys. In healthy people this is usually tolerated; in patients with reduced kidney function, dehydration, or on certain other medications (particularly ACE inhibitors, ARBs, and diuretics), NSAIDs can cause acute kidney injury. Long-term NSAID use can also worsen chronic kidney disease. If you have any kidney disease, discuss NSAID use with your physician before starting.

NSAIDs can raise blood pressure and reduce the effectiveness of many blood pressure medications. If you're taking NSAIDs regularly, your blood pressure should be checked periodically.

NSAIDs affect platelet function and can prolong bleeding. This matters most in patients on blood thinners and before surgical procedures. Most surgeons ask patients to stop NSAIDs several days before elective surgery.

Less common effects include drowsiness, dizziness, ringing in the ears, skin rash, sensitivity to sunlight, and swelling in the ankles. Rare but serious effects that warrant immediate physician contact: changes in heart rhythm, shortness of breath, severe headache, dark stools, yellow eyes or skin, or unusual bruising.

Tell your physician before starting an NSAID if you have any of the following:

• Kidney disease.
• Heart failure, coronary artery disease, or prior heart attack or stroke.
• High blood pressure.
• Stomach or duodenal ulcer disease.
• Asthma — a small percentage of asthmatics have NSAID-sensitive asthma that can be severely triggered.
• Bleeding disorders or use of blood thinners (warfarin, apixaban, rivaroxaban, dabigatran, clopidogrel).
• Pregnancy — NSAIDs are generally avoided in the third trimester and often earlier.
• Age over 65 — the risk profile of NSAIDs shifts significantly with age, and lower doses, shorter courses, and topical formulations become more attractive.

NSAIDs interact with a number of common medications:

• Blood thinners (warfarin, apixaban, rivaroxaban, dabigatran, clopidogrel) — combined bleeding risk. Requires careful coordination.
• ACE inhibitors and ARBs (lisinopril, losartan, and others) — combined kidney risk and reduced blood pressure control.
• Diuretics (furosemide, hydrochlorothiazide) — reduced diuretic effect and increased kidney risk.
• Lithium — NSAIDs can raise lithium levels to toxic ranges.
• Methotrexate — NSAIDs can raise methotrexate levels.
• Alcohol — combined GI bleeding risk.

• Don't share NSAID prescriptions or take medications belonging to friends or family.
• Don't drink alcohol with NSAIDs.
• Tell every physician who prescribes for you — and every pharmacist — that you're on an NSAID.
• For long-term NSAID use, expect periodic blood tests (kidney function, blood count) and blood pressure checks.
• Don't take multiple NSAIDs at the same time. Taking ibuprofen and naproxen together, or either with prescription NSAIDs, multiplies side effects without improving pain control.
• Low-dose daily aspirin (81 mg) prescribed for cardiovascular protection is a separate matter from NSAID use for pain, but ibuprofen taken close to daily low-dose aspirin can block the aspirin's cardiovascular benefit. Ask your pharmacist how to space these.
• Consider topical NSAIDs when pain is focal — they carry much less systemic risk.

If pain isn't responding to NSAIDs or you're needing them long-term, that's a good time to see a pain specialist. Call Newport Pain Management at (949) 759-8400 to schedule an evaluation.

This article is for general education and is not a substitute for individual medical advice.