Opioids work by binding to opioid receptors (mu, kappa, and delta) found in the brain, spinal cord, peripheral nervous system, and GI tract. These receptors are part of a group known as G protein-coupled receptors (GPCRs), which are essential for various nervous system functions including pain modulation. When opioids bind to these receptors, they trigger a change in the receptor's structure, activating G proteins that split into subunits, leading to changes in cellular functions such as reducing cyclic adenosine monophosphate (cAMP) production.
This activation results in the closing of calcium channels and opening of potassium channels, causing neurons to hyperpolarize and reduce neurotransmitter release at synapses. This decrease in neurotransmitter release diminishes the pain signals sent to the brain. Endogenous opioids like enkephalins (natural pain-relieving chemicals) and exogenous opioids like morphine mimic these actions at opioid receptors, particularly affecting areas involved in pain perception such as the midbrain, pons, medulla, and spinal cord.
