USMLE (United States Medical Licensing Examination) Step 1 Practice Exam

What is the mode of action of opioids on mu receptors leading to pain transmission termination?

1. Inhibition of transmitter release

2. Activation of adenylyl cyclase

3. Inhibition of K+ efflux

4. Inhibition of Ca2+ conductance

The correct answer is: Inhibition of K+ efflux

Opioids primarily exert their analgesic effects through their action on mu receptors, which are a type of opioid receptor found in the central nervous system. The correct answer relates to the mechanism by which opioids inhibit pain transmission. When opioids bind to mu receptors, one of the key actions is the inhibition of presynaptic calcium channels. This inhibition reduces the influx of calcium ions into the presynaptic neuron, which is essential for the release of neurotransmitters such as substance P and glutamate that propagate pain signals. With decreased neurotransmitter release, the overall transmission of pain signals to the post-synaptic neurons is diminished, leading to pain relief. While the other options present mechanisms that are relevant to opioid pharmacology, they do not directly describe the primary action on mu receptors in the context of pain signal termination. For example, adenylyl cyclase activation does not occur with opioid receptor activation; instead, opioids typically inhibit adenylyl cyclase activity, leading to a decrease in cyclic AMP levels. K+ efflux is not inhibited—in fact, opioids can lead to increased K+ conductance, contributing to hyperpolarization of neurons. Thus, the essential mechanism by which opioids terminate pain transmission involves the