NSAIDs have anti-inflammatory (reduce inflammation), analgesic (relieve pain) and antipyretic (lower temperature) effects. Although different NSAIDs have different structures, they all work by blocking cyclooxygenase (COX) enzymes. There are two main types of COX enzymes: COX-1 and COX-2. Both types produce prostaglandins; however, the main function of COX-1 enzymes is to produce baseline levels of prostaglandins that activate platelets and protect the lining of the gastrointestinal tract, whereas COX-2 enzymes are responsible for releasing prostaglandins after infection or injury. Prostaglandins have a number of different effects, one of which is to regulate inflammation. Most NSAIDs inhibit both enzymes, although a few are available that mainly inhibit COX-2. The pain-relieving and anti-inflammatory effects of NSAIDs are mainly due to inhibition of COX-2, and their unwanted side effects are largely due to inhibition of COX-1.
Three trials (n = 918) compared the effects of NSAIDs to those of placebo on pain reduction. The pooled mean difference showed comparable pain reduction (visual analogue scale, 0 to 100) in the NSAIDs and placebo groups ( MD -, 95% CI - to ). Heterogeneity was high (I 2 = 82%), and the quality of the evidence was very low. When we excluded one trial with a short follow-up of eight hours, the mean difference further decreased ( MD -, 95% CI - to ). Three trials (n = 753) compared NSAIDs to placebo regarding global improvement. We found low - quality evidence that NSAIDs are more effective than placebo with a risk ratio of (95% CI to ). One trial (n = 214) studied the effect of NSAIDs on disability, finding very low - quality evidence that NSAIDs are no more effective than placebo on disability. Four trials (n = 967) comparing NSAIDs to placebo reported adverse effects , with low - quality evidence that the risk for adverse effects is higher in the NSAID group than in the placebo group ( RR , 95% CI to ). The adverse effects reported in this review are consistent with those previously reported in the literature.