NSAIDs: Everything You Need to Know About Anti-Inflammatory Pain Relief

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly consumed medication classes worldwide. Available both over-the-counter and by prescription, they are used to treat pain, inflammation, and fever. Yet despite their familiarity, many people underestimate the risks of long-term or improper NSAID use.

All NSAIDs work by inhibiting cyclooxygenase (COX) enzymes, which convert arachidonic acid into prostaglandins — lipid compounds that mediate inflammation, pain, and fever. There are two main COX isoforms: COX-1 (constitutively expressed, protects the stomach lining and supports platelet function) and COX-2 (induced at sites of inflammation). Traditional NSAIDs like ibuprofen and naproxen inhibit both COX-1 and COX-2, while selective COX-2 inhibitors (celecoxib) primarily target COX-2.

Ibuprofen (200–800 mg per dose) has the shortest duration of action (4–6 hours) and is among the gentlest on the stomach. Naproxen (250–500 mg) lasts 8–12 hours, making it convenient for chronic conditions. Diclofenac is one of the most potent NSAIDs and is available in oral, topical, and injectable forms. Aspirin uniquely causes irreversible COX-1 inhibition, which is why low-dose aspirin (75–100 mg) is used for cardiovascular prevention. Celecoxib selectively inhibits COX-2, reducing gastrointestinal risk but potentially increasing cardiovascular risk.

Because COX-1-derived prostaglandins protect the gastric mucosa, traditional NSAIDs increase the risk of peptic ulcers, GI bleeding, and perforation. This risk is dose-dependent and increases with duration of use, age over 65, concurrent anticoagulant use, and history of GI ulcers. Proton pump inhibitors (omeprazole, pantoprazole) are often co-prescribed for gastroprotection in high-risk patients.

All NSAIDs (except low-dose aspirin) can increase the risk of heart attack and stroke, particularly with long-term use. Diclofenac carries the highest cardiovascular risk among common NSAIDs, while naproxen may have the lowest. NSAIDs also reduce renal blood flow and can cause fluid retention, hypertension, and acute kidney injury — particularly dangerous in patients with pre-existing kidney disease or those taking ACE inhibitors or diuretics.

Use the lowest effective dose for the shortest necessary duration. Prefer topical NSAIDs (diclofenac gel) for localized pain when possible — they achieve local tissue concentrations with minimal systemic absorption. Avoid combining two oral NSAIDs. Do not use NSAIDs in the third trimester of pregnancy (risk of premature closure of the ductus arteriosus).

Seek medical attention if you experience dark or bloody stools, severe stomach pain, unexplained weight gain or swelling, or chest pain while taking NSAIDs. Patients with heart disease, kidney disease, or a history of GI bleeding should consult their doctor before using any NSAID, including over-the-counter options.