Injection of morphine loco dolenti recommended as early as 1876

The peripheral site of action of opioids was proved some 20 years ago. The concept of the peripheral action of morphine, however, appears to be over 100 years older. We report on the contents of a paper, presented on 28 April 1876 at the meeting of the Finnish Medical Association ("Finska Läkarsällskapet"), on the use of morphine and its sites of action. The author was Professor Knut Felix von Willebrand, whose details are included. Prof. v. Willebrand starts by focusing on several unwanted side effects, often seen in connection with morphine administration, and advises how they can be avoided by using the pupils of the eye as a manometer for tolerance of morphine, as suggested by Vibert. After having presented four case reports which illustrate the use of morphine in his own practice, Prof. v. Willebrand explains his conception of the sites of action of morphine. The paper gives a lively picture of the use of morphine about 125 years ago. Furthermore, it indicates that Prof. v. Willebrand believed firmly in the peripheral site of action of morphine and recommended to inject morphine loco dolenti whenever possible.