Edward Stone (natural philosopher) piece of bark from a willow tree and was struck by its extremely bitter taste. Knowing that the bark of the Peruvian cinchona tree − from which quinine (used in the treatment of malarial fevers) is derived − has a similarly bitter taste, he surmised that the willow might also have therapeutic properties. Stone's interest in willows was due to the ancient "doctrine of signatures" – whereby the cause of a disease offers a clue to its treatment. According to Stone: "As this tree delights in a moist or wet soil, where agues chiefly abound, the general maxim that many
Analgesic tolerance, which may be of particular concern regarding patients suffering with chronic pain and requiring an analgesic over long periods. Opioid tolerance is often addressed with opioid rotation therapy in which a patient is routinely switched between two or more non-cross-tolerant opioid medications in order to prevent exceeding safe dosages in the attempt to achieve an adequate analgesic effect. Opioid tolerance should not be confused with opioid-induced hyperalgesia. The symptoms of these two conditions can appear very similar but the mechanism of action is different. Opioid-induced hyperalgesia is when exposure to opioids increases the sensation of pain (hyperalgesia) and can