The Role of COX-2 in Acute Pain and the Use of Selective COX-2 Inhibitors for Acute Pain Relief

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain. Cyclooxygenase (COX) enzyme is of particular interest because it is the major target of NSAIDs. Although NSAIDs are remarkably effective in the management of pain and inflammation, their use is limited by several adverse effects including gastrointestinal bleeding and ulceration, impaired renal function, and inhibition of platelet aggregation. Discovery of a second cyclooxygenase, COX-2, led to the hypothesis that NSAID side effects could be decreased, as the inhibition of COX-2 is more directly implicated in ameliorating inflammation while the inhibition of COX-1 is related to adverse effects in the GI tract. This stimulated the development of selective COX-2 inhibitors (coxibs) that are better tolerated than nonselective NSAIDs but comparable in analgesic efficacy. This article provides an overview on the therapeutic use of selective COX-2 inhibitors for relief of acute pain, largely based on clinical trials in patients undergoing the surgical removal of impacted third molars, with focus on analgesic efficacy and the potential safety associated with their use compared to dual COX-1/COX-2 inhibitors.

Current concepts regarding the pathogenesis of necrotizing enterocolitis

“…Prostanoids are produced by a variety of tissues and cell types, and their functions are essential: mice completely lacking COX activity die early during post-partum [89]. Prostanoids regulate cell proliferation, apoptosis and migration [90][91][92][93], gastrointestinal secretion [94], smooth muscle contraction and relaxation, body temperature, pain sensation, and inflammation by signaling through their cognate G-protein coupled receptors [95][96][97][98].…”

The selective and non-selective cyclooxygenase inhibitors valdecoxib and piroxicam induce the same postoperative analgesia and control of trismus and swelling after lower third molar removal

“…The therapeutic effect of these medications is based on the inhibition of cyclooxygenases (COX), which determines an inhibition of prostaglandin production (7). However, their use has been associated with a large number of adverse effects, including gastrointestinal ulceration and bleeding, inhibition of platelet aggregation, and alterations in renal function (7)(8)(9).…”

“…Three COX isoforms are known: COX-1, a constitutive form expressed in almost all tissues, COX-2, which is predominantly induced and constitutively expressed in a limited number of tissues (renal medulla, prostate, brain, and endothelium) (7,10,11), and COX-3, a COX-1-derived protein, most abundantly found in the cerebral cortex and heart (12). COX-2 is believed to be the main isoenzyme for pro-inflammatory prostaglandin production (7).…”

“…COX-2 is believed to be the main isoenzyme for pro-inflammatory prostaglandin production (7). Thus, despite their high cost, COX-2 selective inhibitors such as coxibs have been extensively used in order to selectively inhibit COX-2, but not COX-1, resulting in therapeutic effects comparable with those of conventional NSAIDS, but with less adverse reactions for patients (7,13). It is worth mentioning that recent reports have suggested an increased risk of cardiovascular events for patients taking coxibs.…”

QSAR rationales for the 1,2-diarylcyclopentenes as prostaglandin EP1 receptor antagonists: Potentially useful in the treatment of inflammatory pain

“…The first-line treatments for inflammatory pains, including chronic low back pain, pain associated with osteoarthritis and rheumatoid arthritis, are selective COX-2 inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs), which interrupt the biosynthesis of PGE2 and other prostaglandins (PGs) [6][7][8][9][10][11]. The gastrointestinal side effects associated with NSAIDs have been successfully reduced with selective COX-2 inhibitors [12][13][14].…”