Pain has been one of the greatest factors to affect the course of human events for scarcely any man has escaped its throes. As classical authors related the lives of heroes, as medieval chroniclers told the legends of saints and biographers wrote of philosophers, artists, soldiers, inventors, scientists, and reformers, invariably one chapter of these biographies were entitled Pain. The emotional and physical consequences of persistent severe pain has been emphasized repeatedly by scientists, writers and poets. Milton wrote in Paradise lost: "Pain is perfect misery, the worst of evils, and excessive, overturns All Patience".

It is natural that from the beginning humankind should have engaged its energies to understand the nature of pain and make attempts to control it. People living in Mesopotamia (the area that is now Iraq) about 3000 BC, began to build cities and develop a system of writing. The asu was one of several practitioners to whom the populace might have turned for pain relief. His colleagues could have included a priest-physician and an exorcist. The asu used drugs and surgery to attain results. An eight century BC Assyrian alabaster relief depicts a priest carrying opium poppies during a ceremony, indicating that opium was one of the drugs used. In Egypt pain was considered the result of spirits of the dead entering an individual's body through an ear or nostril. In Hearst papyrus, 1550 BC, clinicians treating pain were advised, to prescribe the drinking of a mixture of beer, juniper and yeast, to be swallowed by the patient over a period of four days. The medical papyruses reveal substantial use of hyoscyamus, scopolamine, and the opium poppy. The broad pharmacopoeia and wide range of surgical tools in use in ancient India suggests that pain was treated when possible. In China, medical practice was based primarily on the work of emperor Shen Nung (2800 BC), who was an authority on the medical use of herbs, and Huang Ti (2600 BC), who is generally credited as having originated the Nei Ching that body of medical knowledge describing acupuncture. Virtually every illness, sign, symptom or pain was thought to be amenable to correction by acupuncture, which allowed the practitioner to correct the imbalance of the yang or yin by inserting needles into any of the points along 12 meridians that transverse the body.

The vast Chinese pharmacopoeia included ephedrine; it also included ginseng; administered to sedate overwrought people; the willow plant, containing salicylic acid, helpful for rheumatic pain; and the Siberian wort, an antispasmodic, used to relieve back pain.