Opioids interact with opioid receptors in the nervous system. These receptors are the sites of action for the endorphins, compounds that already exist in the body and are chemically related to the opioid drugs that are prescribed for pain.
Endogenous opioid peptides and exogenous opioid alkaloids regulate nociceptive transmission at key points in the pain modulatory system. Modulation occurs through a combination of pre-synaptic and post–synaptic actions. Mu opioid receptors are located on the pre-synaptic terminals of nociceptive afferents as well as the dendrites of post-synaptic neurons.1 Nociceptive stimulation of sensory neurons causes calcium ions to enter pre-synaptic sensory terminals, triggering neurotransmitter release. Exogenous opiates reduce the release of neurotransmitters by activating pre-synaptic opioid receptors. Activated receptors restrict calcium ion channels in sensory terminals. Reduced calcium ion influx inhibits the release of neurotransmitters from the dorsal horn terminals of primary afferent nociceptors. This causes analgesia as nociceptive transmission from pre-synaptic to post–synaptic neurons is reduced.2 Opiates also produce analgesia by activating potassium ion channels post–synaptic opioid receptors. This causes potassium ion efflux from the post–synaptic neuron. The efflux of potassium ions causes a build up of a negative charge on the inner surface of the neuron. This hyper-polarization decreases the amplitude of the post–synaptic firing of the neuron resulting in a decrease in signaling to pain centers in the brain.3, 4
