NSAIDS have antipyretic activity and can be used to treat fever.   Fever is caused by elevated levels of prostaglandin E2 , which alters the firing rate of neurons within the hypothalamus that control thermoregulation.   Antipyretics work by inhibiting the enzyme COX, which causes the general inhibition of prostanoid biosynthesis ( PGE2 ) within the hypothalamus .   PGE2 signals to the hypothalamus to increase the body's thermal set point.   Ibuprofen has been shown more effective as an antipyretic than paracetamol (acetaminophen).   Arachidonic acid is the precursor substrate for cyclooxygenase leading to the production of prostaglandins F, D & E.
A Cochrane review of the analgesic efficacy of paracetamol and ibuprofen in the treatment of post-operative pain, concluded that combinations of paracetamol plus ibuprofen provided better analgesia than either medicine alone. 12 It was also concluded that the combination treatment reduced the need for additional analgesia to be administered and reduced the risk of adverse events occurring. 12 A study of approximately 900 patients using paracetamol or ibuprofen, or a combination of the two, for the treatment of osteoarthritis of the knee found significantly more patients achieved pain control at ten days and at 13 weeks with the combination treatment compared to paracetamol alone, but there was not a statistically significant difference compared to using ibuprofen alone. 15 In contrast, a small study of 90 patients randomised to one of three treatment groups in an emergency department setting found that combination treatment with paracetamol and ibuprofen did not provide more effective pain relief following musculoskeletal injury compared to either medicine alone. 16