Question: Ibuprofen and Tylenol are well known anti-inflammatory drug as well as painkillers. However, I was given Oxycodone as pain medication after a recent surgery. My question is, what is the difference between the various pain medication and their mechanism of action.

Answer: Pain is the sensation we experienced when harmful stimuli is applied to our body. The inflammatory mediators released from damaged tissue initiate pain transmission by the activation of nociceptors, the receptor responsible for detecting unpleasant mechanical, thermal or chemical stimuli. After the stimuli is transformed into electric signals in neurons, it passes through the afferent nerve fibers to the spinal cord neurons. The information will be carried by these spinal cord neurons though thespinothalamic tract or spinoreticular tract to the higher ordered brain region like the periaqueductal gray and cortical region.1

Ibuprofen is a member of Nonsteroidal Anti-inflammatory drugs (NSAIDs). They can inhibit a type of enzyme called cyclo-oxygenase (COX), which can catalyze the production of prostaglandin, a type of inflammatory mediator. COX has two types, COX-I and COX-II. COX-II is commonly found at the inflammatory or wound site, and is related to pain transduction. By inhibiting the COX, NSAIDs can reduce the production of prostaglandin, and reduce the activation of the nociceptor, and eventually reduce the pain sensation at the peripheral nerve endings.

The effective chemical in Tylenol is call acetaminophen. Unlike NSAIDs, acetaminophen does not block the synthesis of prostaglandin at peripheral nerve ending. Instead, it is thought to be interacting with cyclooxygenase pathway in central nervous system (CNS), however, the detailed mechanism is still unknown.

Lastly, Oxycodone belongs to another family of analgesic, the opioids. Opioids act on opioid receptors in the CNS, especially on μ opioid receptors.3 Opioid receptors are mainly inhibitory because they are coupled with the Gi protein, a type of messenger protein responsible for transducing inhibitory signals in cells. As opioids activate the opioid receptors on neurons at dorsal horn of the spinal cord, the signal cascade would cause hyperpolarization of the neurons and reduce their activity. As a result, this reduces the excitatory transmitter released onto the next neuron.4 Opioids can also act on periaqueductal grey (a brain region specifically responsible for pain regulation and reduction), enhancing the descending inhibition to the lower level pain transduction neural network.1,5  From these analysis about pain medications and their mechanism of action, we can learn that even the two well-known painkillers are acting differently in our body.

  • Lei Y.


  1. 1.Reddi, D., Curran, N., & Stephens, R. (2013). An introduction to pain pathways and mechanisms.British Journal of Hospital Medicine, 74(Sup12), C188–C191. doi:10.12968/hmed.2013.74.sup12.c188
  2. Comfort: Pain mechanisms. (2002). Retrieved June 28, 2016, from
  3. Gregory, T. Pain medications and mechanisms of action. Retrieved June 28, 2016, from
  4. Bovill, J. (1997). Mechanisms of actions of opioids and non-steroidal anti-inflammatory drugs.European journal of anaesthesiology. Supplement., 15, 9–15. Retrieved from
  5. 5. Behbehani, M. (1995). Functional characteristics of the midbrain periaqueductal gray. Progress in neurobiology., 46(6), 575–605. Retrieved from