The main pharmacological action of nonsteroidal anti-inflammatory drugs (NSAIDs) is the blockade of cyclooxygenase (COX) enzymes. NSAIDs inhibit the activity of COX enzymes, which are crucial in the conversion of arachidonic acid to prostaglandins and thromboxanes. Prostaglandins play a key role in the mediation of inflammation, pain, and fever. By inhibiting COX enzymes, NSAIDs effectively reduce these symptoms.

There are two main isoforms of the COX enzyme: COX-1 and COX-2. COX-1 is expressed constitutively in many tissues and is important for maintaining normal physiological functions such as gastric mucosal protection and platelet aggregation. COX-2 is inducible and primarily expressed at sites of inflammation. Traditional NSAIDs generally inhibit both COX-1 and COX-2, which explains their anti-inflammatory benefits as well as some gastrointestinal side effects.

The other options are incorrect because:
- Inhibition of the lipoxygenase pathway affects leukotriene production but is not the primary action of NSAIDs.
- Suppression of tumor necrosis factor-alpha (TNF-α) is the primary mechanism of biologic drugs used for autoimmune conditions, not NSAIDs.
- Activation of opioid receptors is the mechanism of opioid analgesics, not NSAIDs.

In summary, the defining pharmacological action of NSAIDs is the inhibition of cyclooxygenase enzymes leading to decreased prostaglandin synthesis, resulting in their anti-inflammatory, analgesic, and antipyretic effects.

Reference: Goodman & Gilman's The Pharmacological Basis of Therapeutics, 13th Edition, Chapter 44/Pages 997-1010