Treating osteoarthritis pain: mechanisms of action of acetaminophen, nonsteroidal anti-inflammatory drugs, opioids, and nerve growth factor antibodies

Postgrad Med. 2021 Nov;133(8):879-894. doi: 10.1080/00325481.2021.1949199. Epub 2021 Jul 12.


Osteoarthritis (OA) is a common difficult-to-treat condition where the goal, in the absence of disease-modifying treatments, is to alleviate symptoms such as pain and loss of function. Acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids are common pharmacologic treatments for OA. Antibodies directed against nerve growth factor (NGF-Abs) are a new class of agents under clinical investigation for the treatment of OA. This narrative review describes (and uses schematics to visualize) nociceptive signaling, chronification of pain, and the mechanisms of action (MOAs) of these different analgesics in the context of OA-related pain pathophysiology. Further, the varying levels of efficacy and safety of these agents observed in patients with OA is examined, based on an overview of published clinical data and/or treatment guidelines (when available), in the context of differences in their MOAs.

Keywords: Osteoarthritis; acetaminophen; mechanism of action; nerve growth factor; nonsteroidal anti-inflammatory drugs; opioids; pain.

Publication types

  • Review

MeSH terms

  • Acetaminophen / therapeutic use*
  • Analgesics, Non-Narcotic / therapeutic use*
  • Analgesics, Opioid / therapeutic use*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Osteoarthritis / drug therapy*
  • Pain Management


  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Acetaminophen