Morphine and other opiates mimic the action of natural chemicals, endorphins, produced by the body in response to pain. Endorphins are small-chain peptides that activate endogenous opioid receptors. Opioid receptors are proteins embedded in the cell membrane; opioid agonists bind to the receptors to initiate their effects. The highest density of opioid receptors is found in the limbic system and the spinal cord. Their activation produces feelings of happiness, relaxation, fearlessness, and tolerance to pain.

Morphine sulfate relieves pain by stimulating the mu opiate receptors in the CNS; it also causes respiratory depression, peripheral vasodilation, inhibition of intestinal peristalsis, and stimulation of chemoreceptors that cause vomiting and increase bladder tone. Contraindications include acute asthma, upper airway blockage, hypersensitivity to opiates, and diarrhea resulting from poisoning or toxins.

Generally, severe pain from trauma, burns, and post surgery is treated by injection of strong opioids such as morphine or fentanyl. Mild inflammatory pain such as arthritis is treated by NSAIDs supplemented with weak opiods such as codeine, or pentazocine given orally. Severe cancer pain, arthritis or back pain is treated with strong opioids given by injection or epidurally. Patient controlled analgesia (PCA) systems can be used post operatively. Chronic neuropathic pain does not usually respond well to opioids and may be treated with cannabis preparations in states that allow its use. An epidemic of opioid overdose deaths is, in part, caused by an overuse of opioid prescriptions, and the CDC issued its opioid prescribing guidelines in an attempt to decrease problems related to opioid use.