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Two hundred years before their use was accepted, he advocated a new class of chemical agents as opposed to the popular galenics of the time, which consisted of plant matter. An avid chemist,
Paracelsus described the action of ether on chickens, reporting that this substance "quiets all suffering and relieves all pain". Unfortunately this discovery was not followed by the clinical application of ether until well into the nineteenth century.
Opium's power to relieve pain was widely recognized by the time of the Renaissance.
Paracelsus took the most common forms of opium (powder and a black sticky gum) and combined them with alcohol to form Laudanum. Laudanum was used for the relief of pain well into the ninetieth century.
 During the sixteenth century, the French
surgeon Ambrose Pare' was searching for a way to reduce the pain of limb surgery. He reported
that when a firm ligation was made above the site of operation, bleeding would be better controlled, and pain would be greatly diminished. His method was improved upon in 1784, when James Moore
described his technique, in which a compression apparatus employing a vice that screwed down
on a limb, exerting pressure on the main nerves, was used. In 1875 Johannes Esmarck refined
the method further by substituting a bandage of rubber wound around the proximal portion of the limb. Esmarck's bandage is still in use today, but in a slightly different venue. In 1898 Heinrich Braun established that it was the compression of the nerves that produced the anesthesia. He declared, however, that this method of anesthesia belonged in history. Cocaine was in widespread use by this time, providing Braun and his colleagues with an alternative not available to earlier generations of surgeons.
 Refrigeration anesthesia was discussed by (The
Arabist) Avicenna in his writing describing the range of analgesic's available at that time: "The most powerful of narcotics is opium. . . and the least powerful are snow and ice water". Refrigeration anesthesia was also appreciated in Saxon, England at about the same time
1050 AD.
In 1661 Thomas Bartholin devoted part of a chapter in his medical textbook, De Nivis Usu Medico , to reporting on Severino of Naples' technique of rubbing snow and ice on the surgical incision site. Bartholin wrote of Severino's practice: "When he wishes to conceal the nature of the treatment, in order to make the results seem more astonishing, Severino dyes the snow with ground ultramarine or some other coloring matter". In 1807
Dominique-Jean Larrey, Napoleon's surgeon general, recorded in his memoirs that the -19 degree weather, in the Russian campaign, allowed him to perform painless amputations on the battle field.
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